Primary reattachment of avulsed skin flaps with negative pressure wound therapy in degloving injuries of the lower extremity.

Large avulsed skin flaps of the lower extremity caused by degloving injuries eventually develop skin necrosis in most cases. The current treatment option involves excision of the degloved skin and reapplication as a full- or split-thickness skin graft. We considered that reattachment of avulsed skin flaps without excision would be theoretically beneficial, since some circulation may remain around the connected pedicle and thus facilitate graft take. Furthermore, securing the skin to the original anatomic position is much easier using retained landmarks. We treated a total of 12 patients (13 cases) with degloving injuries of the lower extremity. In all cases, the avulsed skin flap was defatted and sewn back to the original position, then negative-pressure wound therapy was applied over those grafts as a bolster for approximately 7 days. Most of the avulsed skin flap took excellently, particularly close to the connected pedicle. Nine cases did not need any additional surgical procedures. Four cases required secondary skin graft for a small area of open wound due to partial necrosis of the defatted skin, as well as the raw surface left by the primary skin defect in the initial operation. Primary reattachment of the avulsed skin flaps without excision is convenient and efficient to cover the open wound over the exposed fascia and periosteum in degloving injuries. This would potentially offer a better alternative to definitive wound closure.

Direct observation of long-lived isomers in 212Bi.

Long-lived isomers in (212)Bi have been studied following (238)U projectile fragmentation at 670 MeV per nucleon. The fragmentation products were injected as highly charged ions into a storage ring, giving access to masses and half-lives. While the excitation energy of the first isomer of (212)Bi was confirmed, the second isomer was observed at 1478(30) keV, in contrast to the previously accepted value of >1910 keV. It was also found to have an extended Lorentz-corrected in-ring half-life >30 min, compared to 7.0(3) min for the neutral atom. Both the energy and half-life differences can be understood as being due a substantial, though previously unrecognized, internal decay branch for neutral atoms. Earlier shell-model calculations are now found to give good agreement with the isomer excitation energy. Furthermore, these and new calculations predict the existence of states at slightly higher energy that could facilitate isomer deexcitation studies.

Improvement of tardive dyskinesia and dystonia associated with aripiprazole following a switch to quetiapine: case report and review of the literature.

WHAT IS KNOWN AND OBJECTIVE: Aripiprazole has a low risk of extrapyramidal symptoms. Switching to aripiprazole has been reported to improve tardive dyskinesia caused by other medications. The authors report a case and review previous reports of dystonia and dyskinesia associated with aripiprazole. CASE SUMMARY: We present a case of a 22-year-old man with schizophrenia who experienced dyskinesia and dystonia associated with aripiprazole. Switching from olanzapine to aripiprazole resulted in worsening dyskinesia and new onset of dystonia. The patient's dyskinesia and dystonia improved after switching from aripiprazole to quetiapine therapy. WHAT IS NEW AND CONCLUSION: There were several previous case reports on dyskinesia and dystonia associated with aripiprazole medication. The risk factors for tardive dyskinesia include older age and female sex. However, our case was a male patient who was younger compared with the previous cases and so should have been less at risk for dyskinesia in comparison with the previous cases. The effects of aripiprazole can include tardive movement disorders. Dyskinesia, dystonia and psychotic symptoms were improved with relatively small dose of quetiapine in this case. Whether some second-generation antipsychotics are more effective than others in the treatment of tardive dyskinesia remains unclear.

Regulation of muscle genes by moderate exercise.

Moderate-intensity exercise at the lactate threshold (LT) is considered to be a safe and effective training regimen for improving metabolic syndrome. The aim of the current study was to investigate the effects of moderate exercise performed at the LT on skeletal muscle gene expression. 6 healthy men participated in cycle ergometer training at LT, 60 min/d, 5 d/wk for 12 wks. Muscle samples were collected after 5 d of training, and then 2 d after training at wks 6 and 12. Quantitative real-time PCR analysis revealed that the expression of peroxisome proliferator activated receptor co-activated 1alpha was significantly increased at 1 h after the training session on day 5. Moreover, using serial analysis gene expression, we found that moderate training for 6 and 12 wks simultaneously induced the expression of a number of metabolic genes involved in the TCA cycle, beta-oxidation, and electron transport. Furthermore, several genes encoding antioxidant enzymes and contractile apparatus were induced. The expression levels of 233 novel transcripts were also altered in response to moderate exercise. Thus, moderate training at the LT is a sufficient stimulus to induce the expression of numerous genes implicated in the development of metabolic syndrome, transcripts involved in the contractile apparatus, and novel transcripts.

Schottky mass measurement of the 208Hg isotope: implication for the proton-neutron interaction strength around doubly magic 208Pb.

Time-resolved Schottky mass spectrometry has been applied to uranium projectile fragments which yielded the mass value for the 208Hg (Z=80, N=128) isotope. The mass excess value of ME=-13 265(31) keV has been obtained, which has been used to determine the proton-neutron interaction strength in 210Pb, as a double difference of atomic masses. The results show a dramatic variation of the strength for lead isotopes when crossing the N=126 neutron shell closure, thus confirming the empirical predictions that this interaction strength is sensitive to the overlap of the wave functions of the last valence neutrons and protons.

Anatomic study for pubic medullary screw insertion.

PURPOSE: To study the anatomy of the pubic ramus and adjacent structures in 160 Japanese to establish a safer pubic screw fixation technique. METHODS: 80 male and 80 female Japanese aged 16 to 89 (mean, 50) years (10 persons in each decade of age) underwent 3-dimensional computed tomographic scanning of their pelvises. The angle at which the screw should be targeted, the appropriate length of the screw, the size of the canal for screw insertion, and the proximity to the bladder, iliac artery, and iliac vein were determined. Correlations between the canal diameters (of the acetabular, base, and parasymphyseal areas) and body features (age, height, and weight) were analysed. RESULTS: In men and women respectively, the appropriate mean screw length was 124.6 and 123.8 mm; the guide wire should be targeted at a mean of 66 degrees and 67 degrees cephalad and 54.1 degrees and 55.9 degrees laterally for insertion of a retrograde pubic screw; the minimum distances from the pubis to the bladder/iliac artery/ iliac vein were 0 and 0 mm/4.9 and 4.6 mm/0.8 and 0.2 mm. In both men and women, the canal diameters at the base were positively correlated to weight. In women, the canal diameters at the parasymphyseal area were correlated to height and weight. Canal diameters at the acetabulum were not correlated to height and weight. CONCLUSION: Pubic screw fixation may be potentially disastrous (owing to joint penetration and iliac vein injury) and should be performed with caution. When the canal diameter at the acetabulum is extremely narrow, plate fixation, computer-assisted surgery, or changing to a smaller-diameter screw is recommended.

Adenoviral-mediated gene transfer of ectodysplasin-A2 results in induction of apoptosis and cell-cycle arrest in osteosarcoma cell lines.

The extremely poor prognosis of patients with metastatic osteosarcoma indicates the need for novel therapeutic approaches. Ectodysplasin-A2 (EDA-A2) is a recently isolated member of the tumor necrosis factor superfamily that binds to X-linked ectodermal dysplasia receptor (XEDAR). In this report, we have analyzed the biological activity of EDA-A2 against osteosarcoma-derived cell lines. We report that XEDAR is expressed in cell lines derived from osteosarcoma and adenoviral-mediated expression of EDA-A2 in these cells results in the induction of apoptosis via caspase activation and cell-cycle arrest in the G(0)/G(1) phase. Treatment with EDA-A2 also upregulates the expression of alkaline phosphatase, a marker of osteogenic differentiation, in a caspase-dependent fashion. Collectively, our results suggest that EDA-A2 may be a promising agent for the gene therapy of osteosarcoma.

Gene expression profile of sprinter's muscle.

We have characterized the global gene expression profile in left vastus lateralis muscles of sprinters and sedentary men. The gene expression profile was analyzed by using serial analysis of gene expression (SAGE) method. The abundantly expressed transcripts in the sprinter's muscle were mainly involved in contraction and energy metabolism, whereas six transcripts were corresponding to potentially novel transcripts. Thirty-eight transcripts were differentially expressed between the sprinter and sedentary individuals. Moreover, sprinters showed higher expressions of both uncharacterized and potentially novel transcripts. Sprinters also highly expressed seven transcripts, such as glycine-rich protein, myosin heavy polypeptide (MYH) 2, expressed sequence tag similar to (EST) fructose-bisphosphate aldolase 1 isoform A (ALDOA), glyceraldehyde-3-phosphate dehydrogenase and ATP synthase F0 subunit 6. On the other hand, 20 transcripts such as MYH1, tropomyosin 2 and 3, troponin C slow, C2 fast, I slow, T1 slow and T3 fast, myoglobin, creatine kinase, ALDOA, glycogen phosphorylase, cytochrome c oxidase II and III, and NADH dehydrogenase 1 and 2 showed lower expression levels in the sprinters than the sedentary controls. The current study has characterized the global gene expressions in sprinters and identified a number of transcripts that can be subjected to further mechanistic analysis.

Recurrent herpes simplex virus infection in a patient with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy associated with L29P and IVS9-1G>C compound heterozygous autoimmune regulator gene mutations.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) has characteristic clinical features with organ-specific autoimmune polyendocrine diseases and candidiasis, caused by the mutations of autoimmune regulator (AIRE) gene. Although almost all patients are complicated with mucocutaneous candidiasis, no apparent susceptibility to other infections has yet been reported. We herein report that a patient with APECED suffered from recurrent herpes simplex virus type 1 (HSV-1) infection after severe primary herpetic stomatitis, associated with sequential HSV-1 isolates of the same genomic profile, consistent with endogeneous recurrence. Thus, not only candidiasis but also HSV infection should receive more attention in patients with APECED, with treatment being administered accordingly.

Suppression of tumor growth by intra-muscular transfer of naked DNA encoding adrenomedullin antagonist.

We have recently reported that the intra-tumoral injection of adrenomedullin (AM) antagonist (AMA; AM (22-52)) peptides significantly reduced the in vivo growth of a pancreatic cancer cell line in severely combined immunodeficient (SCID) mice. In the present study, we examined the effects of intra-tumoral and intra-muscular transfers of naked DNA encoding AMA on the in vivo growth of cancer cell lines. We demonstrate that these treatments induce the regression of a pancreatic cancer cell line and a breast cancer cell line inoculated in SCID mice. Furthermore, CD31-positive cells disappear completely from tumor tissues, following treatment, indicating that neo-vascularization is entirely inhibited. These results suggest that the intra-tumoral or intra-muscular transfer of naked DNA encoding AMA might be a promising alternative modality for treating human cancers.

JTP-426467 acts as a selective antagonist for peroxisome proliferator-activated receptor gamma in vitro and in vivo.

AIM: JTP-426467 was identified as a result of screening in search of selective antagonist for peroxisome proliferator-activated receptor gamma (PPARgamma). We examined whether JTP-426467 functioned as a PPARgamma antagonist in vitro and in vivo and investigated physiological effects of JTP-426467. METHODS: The effect of JTP-426467 as a PPARgamma antagonist was studied in a cell-based reporter assay and an adipocyte differentiation assay. Target mRNA expression levels were determined by branched DNA (bDNA) assay. To examine the effects as a PPARgamma antagonist in vivo, a competitive study between JTP-426467 and BRL49653 (rosiglitazone), a PPARgamma agonist, was performed using KK-Ay mice. The effects of JTP-426467 alone after administration to KK-Ay mice were also explored. JTP-426467 antagonized PPARgamma activity in a reporter assay system, but not PPARalpha. RESULTS: JTP-426467 inhibited the expression of hormone-sensitive lipase (HSL) mRNA, an adipocyte-abundant gene, but not PPARgamma itself or cyclophilin mRNA (as constitutive mRNA), and also suppressed triglyceride accumulation in differentiated stromal vascular fraction cells (SVFs). JTP-426467 antagonized PPARgamma agonistic action by BRL49653 in KK-Ay mice on high-fat diet, in terms of plasma glucose, body weight gain and interscapular brown adipose tissue (IBAT) weight. JTP-426467 alone inhibited body weight gain and decreased plasma leptin level in KK-Ay mice. CONCLUSIONS: JTP-426467 acted as a pure and potent PPARgamma antagonist in vitro. Interestingly, JTP-426467 completely antagonized the effects of PPARgamma agonist BRL49653 in an obese diabetic model. JTP-426467 may be a useful tool for the study of PPARgamma in biological and physiological function.

Lack of modulation of Ib inhibition during antagonist contraction in spasticity.

OBJECTIVE: To examine the modulation of non-reciprocal group I (Ib) inhibition during tonic contraction of antagonist muscles in patients with spasticity vs normal subjects. METHODS: The authors studied 10 patients with spastic paraplegia due to cervical compression myelopathy and 16 age-matched normal subjects. Ib inhibition to soleus motoneurons was recorded as the change in size of the H-reflex of the soleus, evoked by conditioning stimulus to the nerve innervating the medial gastrocnemius muscle. The extent of inhibition was studied at rest and during tonic contraction of the pretibial muscles of variable strength. RESULTS: In the resting state, the extent of inhibition in the patients did not differ from normal controls. During antagonist contraction, the extent of inhibition increased both in the normal subjects and patients. The increment was smaller in the patients, especially in those with severe spastic gait. The smaller increment in the inhibition was correlated with the time required to walk 10 m in the patients. CONCLUSION: The authors observed a lack of modulation of Ib inhibition during tonic antagonist contraction in patients with spasticity, especially those with gait disturbance. Disturbed central modulation of non-reciprocal (Ib) interneurons may be responsible for spasticity.

Long-period accelerometer monitoring shows the role of physical activity in overweight and obesity.

CONTEXT: Physical activity (PA) plays an important role in obesity. A new accelerometer has been developed to assess total energy expenditure as well as PA. OBJECTIVE: To investigate the association of PA with overweight and obesity in Japanese men and women, a large cross-sectional study was performed using a single-axis accelerometer. DESIGN, SETTING AND PARTICIPANTS: Population-based cross-sectional study of Japanese 18-84 y of age. Height, body weight and PA were measured in 400 male and 388 female Japanese volunteers from 1999 to 2000. The outcome measurements were overweight and obesity, which are defined as a body mass index >/=25 kg/m(2). PA was measured for 1 to 4 weeks and was then categorized into three activity levels, which were defined as light, moderate and vigorous PA. RESULTS: Prevalence of overweight and obesity was 22.3%. Number of steps and time spent in moderate and vigorous PA per day were lower in overweight and obese individuals. No difference was found in time spent in light PA. Individuals who are in the 4th and 5th quintile of moderate and vigorous PA showed a significantly lower body mass index. When odd ratios (ORs) of overweight and obesity estimated by logistic regression were used as effect measures, overweight and obesity were negatively associated with vigorous PA (ORs=0.91). CONCLUSION: These results indicate that overweight and obese individuals have a lower step rate and are spending less time for moderate to vigorous PA. Participation in vigorous PA is an important predictor of overweight and obesity.

Precision spectroscopy of pionic 1s states of Sn nuclei and evidence for partial restoration of chiral symmetry in the nuclear medium.

Deeply bound 1s states of pi(-) in (115,119,123)Sn were preferentially observed using the Sn(d,3He) pion-transfer reaction under the recoil-free condition. The 1s binding energies and widths were precisely determined and were used to deduce the isovector parameter of the s-wave pion-nucleus potential to be b1=-(0.115+/-0.007)m(-1)(pi). The observed enhancement of |b(1)| over the free piN value (b(free)1/b1=0.78+/-0.05) indicates a reduction of the chiral order parameter, f*pi(rho)2/f2pi approximately 0.64, at the normal nuclear density, rho=rho(0).

The I allele of the angiotensin-converting enzyme gene is associated with an increased percentage of slow-twitch type I fibers in human skeletal muscle.

The insertion (I) allele of the human angiotensin-converting enzyme (ACE) gene is associated with lower serum and tissue ACE activity, and with greater endurance performance and enhanced mechanical efficiency of trained muscle. We tested the hypothesis that the ACE-I allele may be associated with increased slow-twitch fiber, which is more efficient than fast-twitch fiber in low-velocity contraction, by examining the association between the ACE genotype and skeletal muscle fiber (SMF) types in 41 untrained healthy young volunteer subjects (31 males, 10 females, age 24 +/- 3 years). Skeletal muscle samples were taken from the left vastus lateralis using the needle-biopsy method. Slow-twitch type I fibers and fast-twitch type IIa and IIb fibers were classified histochemically based on staining for myosin adenosine triphosphatase (ATPase) activity at different pH values. Amylase-periodic acid-Schiff staining was used to visualize capillaries around fibers. ACE-II subjects had significantly (p < 0.01) higher percentages of type I fibers (50.1 +/- 13.9%vs 30.5 +/- 13.3%) and lower percentages of type IIb fibers (16.2 +/- 6.6%vs 32.9 +/- 7.4%) than ACE-DD subjects. The linear trends for decreases in type I fibers and increases in type IIb fibers from ACE-II --> ID --> DD genotypes were significant as assessed by an analysis of variance. The ratio of type I:II fibers also differed according to the ACE genotype. A multivariate logistic regression analysis showed that the ACE-I allele had significant additive and recessive (codominant) effects on the increased type I fibers and the ratio of type I:II fibers. No specific pattern of capillarization was observed among the three ACE genotypes. In conclusion, the ACE-I allele was associated with increased type I SMF, which may be a mechanism for the association between the ACE genotype and endurance performance.

Association of angiotensin-converting-enzyme gene polymorphism with the depressor response to mild exercise therapy in patients with mild to moderate essential hypertension.

We studied the association of angiotensin I-converting enzyme (ACE) gene polymorphism with the depressor response to exercise therapy in 64 Japanese subjects with mild to moderate essential hypertension. Each subject performed 10 weeks of mild (lactate threshold intensity: approximately 50% maximum oxygen consumption) exercise therapy on a bicycle ergometer. Systolic blood pressure (SPB), diastolic blood pressure (DPB), and mean arterial pressure (MAP) were significantly decreased by exercise therapy in subjects with the ACE-II and ID genotypes but not in DD subjects. The time-by-genotype interaction effects were significant for DBP and MAP. According to a multiple logistic regression analysis, the age- and baseline plasma renin activity-adjusted relative risk (odds ratio) for the lack of a depressor response conferred by the D allele (assuming an additive effect) was 2.72 [95% confidence interval (CI), 1.07-6.91; p = 0.034]; for DD genotypes, as compared with the DI and II genotypes (assuming that the D allele is recessive), it was 11.7 (95% CI, 2.25-60.6; p = 0.003). ACE gene I/D polymorphism is associated with the depressor response of essential hypertensives to mild exercise therapy, which suggests that genetic features may underlie, at least in part, the heterogeneity of the depressor response in essential hypertensives to mild exercise therapy.

Peripheral mechanisms in tremor after traumatic neck injury.

Tremor is a rare manifestation after neck injury, and its physiological mechanism has not been elucidated. We studied the effects of torque loading and ischaemic nerve block on coarse postural tremor in the right upper extremity, which had developed in association with a C7-C8 radiculopathy after traumatic neck injury in a 55 year old man. Loading reduced the tremor frequency from 6.1 Hz to 4.2 Hz with corresponding electromyography (EMG) bursts at the same frequencies as the tremor. Ischaemic nerve block also reduced the tremor frequency from 6.2 Hz to 2.8 Hz, and the time course of the frequency was not in parallel with that of the size of the maximal M wave. A significant reduction of the tremor frequency by loading and ischaemic nerve block indicates a mechanical reflex mechanism underlying the tremor, and association of synchronous EMG bursts suggests an increase in gain in the stretch reflex loop. The stretch reflex loop plays an important role in generation of oscillation in tremor after neck injury.

Abnormal conditioning effect of transcranial magnetic stimulation on soleus H-reflex during voluntary movement in Parkinson's disease.

OBJECTIVES: The objective of this study is to clarify the participation of cortical motor control abnormality in the motor dysfunction of Parkinson's disease (PD), especially at the onset of movement. METHODS: Conditioning effects of transcranial magnetic simulation (TMS) on the soleus (SOL) H-reflex evoked with tibial nerve stimulation were examined in 19 patients with PD and 10 normal volunteers. Experiments were done at rest, during tonic plantarflexion (PF), and at PF onset. Stimulus intensity of TMS was maintained at less than 5% of the motor threshold in each situation. Seven patients underwent pallidotomy and were examined twice, once before and once after the operation. RESULTS: Short latency subthreshold TMS stimulation did not facilitate the SOL H-reflex neither during tonic PF nor at PF onset in the patients with PD, though it was evident in normal subjects. In some patients, paradoxical inhibition appeared at PF onset. The facilitation increase at PF onset, as compared to that at rest, was negatively correlated with the motor part of the unified Parkinson's disease rating scale and with the rigidity grade. Pallidotomy improved both modulation and the clinical scores. CONCLUSIONS: Cortical activity for the proper execution of reciprocal control between the agonist and antagonist seems to be disturbed in PD.