Effects of scalp nerve block on pain and emergence agitation after paediatric nevus surgery: a clinical trial.

BACKGROUND: Pain is considered as being one cause of post-operative emergence agitation (EA) from sevoflurane anaesthesia. The purpose of this study was to investigate the pure effect of post-operative pain on EA after sevoflurane anaesthesia in preschool children undergoing excision of scalp nevi. METHODS: Forty-four children, 1-7 years old, undergoing scalp nevus excision were enrolled. Patients were randomly assigned to two groups: the remifentanil group received single intravenous injection of short-acting synthetic opioid, remifentanil 1 µg/kg just before the scalp incision, and the block group received scalp nerve block with 0.25% ropivacaine after intubation. The end-tidal sevoflurane concentration was maintained around 1.5 vol% unless the mean arterial pressure is out of ±20% range of preoperative values during surgery in both groups. Watcha behaviour scale for EA and face, legs, activity, cry, consolability (FLACC) scale scores for pain were recorded post-operatively. RESULTS: There was no difference in end-tidal sevoflurane concentration between the two groups during surgery and the emergence period. Agitation incidence and scores were not different between the two groups during the recovery period. FLACC scale was significantly lower in the block group than in the remifentanil group at post-anaesthesia care unit (PACU) arrival, at 10 and 20 min after PACU arrival, respectively. CONCLUSION: The scalp nerve block decreased the early post-operative pain after paediatric nevus excision, but it did not decrease the incidence of EA with sevoflurane anaesthesia.

The clinical and histopathological characteristics of early-onset basal cell carcinoma in Asians.

BACKGROUND: Basal cell carcinoma (BCC) is by far the most common cancer in white populations. In addition, recent reports have demonstrated an increasing incidence of BCC in Korea. We have observed a significant number of early-onset BCC cases in which the disease occurred in patients younger than 50 years. OBJECTIVE: To investigate the clinicopathological characteristics of early-onset BCC in an Asian population, specifically in Koreans. METHODS: One hundred and five patients with early-onset BCC were enrolled from a total of 1047 BCC patients who underwent surgery between January 1997 and December 2014 (942 patients over the age of 50 years were designated as the control group). RESULTS: Early-onset BCC accounted for 10.03% of all 1047 cases and the incidence over time displayed an incremental trend. The early-onset group displayed similar results as the control group, with a predominance of female BCC patients and the majority of tumours displaying the following characteristics: small in size, occurring in sun-exposed areas and belonging to the noduloulcerative clinical subtype and nodular histopathological subtype. In comparison with a previous study in a Western population, the incidence of the disease in non-exposed areas of the body, as well as the proportion of tumours of the superficial histological subtype, were lower in Asian patients. CONCLUSION: Although the clinicopathological characteristics of BCC are well-known, these characteristics have not been determined for early-onset BCC in an Asian population. Therefore, this study is the first report on early-onset BCC in Asians, specifically in a Korean patient group.

Brain activation-based sexual orientation in female-to-male transsexuals.

This study was performed to identify the sexual orientation in association with brain activation pattern in response to visual erotic stimuli in female-to-male (FtM) transsexuals by using functional magnetic resonance imaging (fMRI). Eleven FtM transsexuals who have had sex-reassignment surgery to alter their natal bodies with the gender-identity disorder were participated. Brain activation for sexual orientation was induced by visual stimuli with female and male erotic nude pictures compared with emotionally-neutral pictures. During viewing the erotic female pictures, the brain areas dominantly activated consist of the superior frontal gyrus, supplementary motor area, anterior/median cingulate gyri and hypothalamus, whereas during viewing male pictures, the brain areas with predominant activities were the middle frontal gyrus, precentral gyrus, middle temporal gyrus, fusiform gyrus, angular gyrus, precuneus, superior/middle occipital gyri, cerebellar cortex and vermis. These findings demonstrate that the brain activation patterns induced by viewing male or female erotic pictures show some correlation to the sexual orientation opposite to the genetic sex in FtM transsexuals. This study would be helpful to understand the neural mechanism associated with visual sexual arousal in patients with gender disorder.

Vertebral compression fractures may increase mortality in male patients with chronic obstructive pulmonary disease.

BACKGROUND: Vertebral compression fracture (VCF) is frequent in chronic obstructive pulmonary disease (COPD) patients. However, little is known about whether VCF affects mortality in COPD patients. OBJECTIVE: To investigate whether VCFs might increase death in COPD patients. METHODS: In this retrospective cohort study, we enrolled 254 COPD patients with a recent history of hospitalisation due to respiratory problems. Patients were assessed for VCF using quantitative morphometric analyses of lateral chest radiographs; 211 patients received follow-up examinations for 2 years. RESULTS: Of the 211 COPD patients analysed, 60 (28.4%) had VCF at enrolment. During the follow-up period, 33/60 (55.0%) patients with and 46/151 patients (30.5%) without VCF died (P = 0.003, log-rank test). Cox proportional hazard analysis revealed that VCF is an independent risk factor for death after adjusting for age, sex, body mass index, smoking, dyspnoea scale, forced expiratory volume in 1 sec (FEV1) and comorbidities (hazard ratio for VCF = 1.79, 95%CI 1.11-2.89, P = 0.02). CONCLUSION: VCF might be an independent risk factor for death in male COPD patients.

CXC chemokine ligand 12a enhances chondrocyte proliferation and maturation during endochondral bone formation.

OBJECTIVE: We investigated the roles of CXC chemokine ligand 12a (CXCL12a), also known as stromal cell-derived factor-1α (SDF-1α), in endochondral bone growth, which can give us important clues to understand the role of CXCL12a in osteoarthritis (OA). METHODS: Primary chondrocytes and tibial explants from embryonic 15.5 day-old mice were cultured with recombinant mouse CXCL12a. To assess the role of CXCL12a in chondrogenic differentiation, we conducted mesenchymal cell micromass culture. RESULTS: In tibia organ cultures, CXCL12a increased total bone length in a dose-dependent manner through proportional effects on cartilage and bone. In accordance with increased length, CXCL12a increased the protein level of proliferation markers, such as cyclin D1 and proliferating cell nuclear antigen (PCNA), in primary chondrocytes as well as in tibia organ culture. In addition, CXCL12a increased the expression of Runx2, Col10 and MMP13 in primary chondrocytes and tibia organ culture system, implying a role of CXCL12a in chondrocyte maturation. Micromass cultures of limb-bud mesenchymal progenitor cells (MPCs) revealed that CXCL12a has a limited effect on early chondrogenesis, but significantly promoted maturation of chondrocytes. CXCL12a induced the phosphorylation of p38 and Erk1/2 MAP kinases and IκB. The increased expression of cyclin D1 by CXCL12a was significantly attenuated by inhibitors of MEK1 and NF-κB. On the other hand, p38 and Erk1/2 MAP kinase and NF-κB signaling were associated with CXCL12a-induced expression of Runx2 and MMP13, the marker of chondrocyte maturation. CONCLUSION: CXCL12a promoted the proliferation and maturation of chondrocytes, which strongly suggest that CXCL12a may have a negative effect on articular cartilage and contribute to OA progression.

Cbl-independent degradation of Met: ways to avoid agonism of bivalent Met-targeting antibody.

The Met receptor tyrosine kinase, found to be constitutively activated in many tumors, has become a leading target for cancer therapy. Disruptions in Met downregulation have been associated with aggressive tumor progression with several therapeutic strategies addressing this aspect of Met biology. Castias B-lineage lymphoma (Cbl) E3 ligase-mediated degradation, which attenuates Met signaling via ligand-dependent Met internalization, is a major negative regulator of Met expression. It is believed that one of the mechanisms by which the therapeutic anti-Met antibodies induce cancer cell death in Met overexpressing tumors is via internalization and subsequent degradation of Met from the cell surface. However, a previously reported Met-targeting antibody demonstrated intrinsic agonistic activity while being capable of inducing Cbl-mediated degradation of Met, suggesting that Cbl-mediated degradation requires receptor activation and impedes therapeutic application. We have developed a potent and selective bivalent Met-targeting antibody (SAIT301) that invokes Met degradation using an alternative regulator LRIG1. In this report, we demonstrate that LRIG1 mediates degradation of Met by SAIT301 and this degradation does not require Met activation. Furthermore, SAIT301 was able to downregulate Met and dramatically inhibit growth of tumors with low or no Cbl expression, as well as tumors with Met exon 14 deletion that prevents Met binding to Cbl. In summary, we demonstrate the enhanced therapeutic potential of a novel tumor-inhibiting anti-Met antibody, SAIT301, which utilizes a Cbl-independent, LRIG1-mediated Met degradation pathway and thereby avoids the agonism that limits the effectiveness of previously reported anti-Met antibodies.

Dermoscopy of subungual haemorrhage: its usefulness in differential diagnosis from nail-unit melanoma.

BACKGROUND: Subungual haemorrhages are characterized by well-circumscribed dots or blotches with a red to red-black pigmentation, but some cases can be difficult to distinguish from subungual melanoma by the naked eye alone. Dermoscopy has proven to be a useful, noninvasive tool in the diagnosis of pigmented lesions in the nail; however, few dermoscopic studies of subungual haemorrhages have been reported. OBJECTIVES: To investigate characteristic dermoscopic patterns of subungual haemorrhages, and to find distinctive features that can differentiate them from nail-unit melanomas. METHODS: Patients with a confirmed diagnosis of either subungual haemorrhage or nail-unit melanoma at a tertiary university hospital were included in the study. Clinical features and dermoscopic patterns were evaluated. RESULTS: Sixty-four patients with a total of 90 lesions of subungual haemorrhage were enrolled in the study. The majority of cases (84%) showed combinations of more than one colour, while 16% had only one colour. The most common colour of the subungual haemorrhages was purple-black, in 37% of cases. A homogeneous pattern was observed in 92% of cases, globular patterns in 42% and streaks in 39%. Peripheral fading and periungual haemorrhages were found in 54% and 22% of cases, respectively. Destruction or dystrophy of the nail plate was observed in 16% of cases. In the 16 cases of nail-unit melanomas, Hutchinson sign, longitudinal irregular bands or lines, triangular shape of bands, vascular pattern, and ulcerations were found in 100%, 81%, 25%, 6% and 81% of cases, respectively. In contrast, these features were not found in subungual haemorrhages. CONCLUSIONS: Dermoscopy provides valuable information for the diagnosis of subungual haemorrhage and aids in the differential diagnosis from nail-unit melanoma.

Supine linac treatment versus tomotherapy in craniospinal irradiation: planning comparison and dosimetric evaluation.

Craniospinal irradiation (CSI) is the standard treatment of primary intracranial tumour with risk of leptomeningeal dissemination. However, supine setup field-in-field technique does not need inter-fractional junction shift. Recently, the studies of CSI with tomotherapy showed excellent target coverage and tolerable normal organ dose in paediatric patients. The planning comparison and dosimetric difference between conventional radiotherapy and tomotherapy are presented. Three patients with central nervous system germinoma received supine CSI treatment. Normal tissue complication probability calculation was performed for parotid gland, kidney, lens, small bowel, ovary and testis. Homogenous vertebral body coverage for tomotherapy compared with conformal radiotherapy was found. The mean dose to each parotid gland decreased by 7.3 and 10 Gy, respectively, with tomotherapy. The volume of oesophagus and small bowel receiving >10 Gy was significantly lower. The V2, V5, V10 and V20 of the lungs are 81.6, 12.4, 2.3 and 0 % with tomotherapy. Tomotherapy showed excellent homogenous dose distribution through the craniospinal axis (PTV) and higher conformity index.

Induction of striatal neurogenesis enhances functional recovery in an adult animal model of neonatal hypoxic-ischemic brain injury.

While intraventricular administration of epidermal growth factor (EGF) expands the proliferation of neural stem/progenitor cells in the subventricular zone (SVZ), overexpression of brain-derived neurotrophic factor (BDNF) is particularly effective in enhancing striatal neurogenesis. We assessed the induction of striatal neurogenesis and consequent functional recovery after chronic infusion of BDNF and EGF in an adult animal model of neonatal hypoxic-ischemic (HI) brain injury. Permanent brain damage was induced in CD-1 (ICR) mice (P7) by applying the ligation of unilateral carotid artery and hypoxic condition. At 6 weeks of age, the mice were randomly assigned to groups receiving a continuous 2-week infusion of one of the following treatments into the ventricle: BDNF, EGF, BDNF/EGF, or phosphate buffered saline (PBS). Two weeks after treatment, immunohistochemical analysis revealed an increase in the number of BrdU(+) cells in the SVZ and striata of BDNF/EGF-treated mice. The number of new neurons co-stained with BrdU and betaIII-tubulin was also significantly increased in the neostriata of BDNF/EGF-treated mice, compared with PBS group. In addition, the newly generated cells were expressed as migrating neuroblasts labeled with PSA-NCAM or doublecortin in the SVZ and the ventricular side of neostriata. The new striatal neurons were also differentiated as mature neurons co-labeled with BrdU(+)/NeuN(+). When evaluated post-surgical 8 weeks, BDNF/EGF-treated mice exhibited significantly longer rotarod latencies at constant speed (48 rpm) and under accelerating condition (4-80 rpm), relative to PBS and untreated controls. In the forelimb-use asymmetry test, BDNF/EGF-treated mice showed significant improvement in the use of the contralateral forelimb. In contrast, this BDNF/EGF-associated functional recovery was abolished in mice receiving a co-infusion of 2% cytosine-b-d-arabinofuranoside (Ara-C), a mitotic inhibitor. Induction of striatal neurogenesis by the intraventricular administration of BDNF and EGF promoted functional recovery in an adult animal model of neonatal HI brain injury. The effect of Ara-C to completely block functional recovery indicates that the effect may be the result of newly generated neurons. Therefore, this treatment may offer a promising strategy for the restoration of motor function for adults with cerebral palsy (CP).

VEGF gene polymorphisms and susceptibility to rheumatoid arthritis.

OBJECTIVES: To investigate polymorphisms of the VEGF gene in patients with rheumatoid arthritis (RA), their relationship to clinical features and the radiographic progression of joint disease. METHODS: One hundred and forty patients with RA and 149 healthy unrelated controls were recruited. We examined four polymorphisms of the VEGF gene which are reported to be associated with production of vascular endothelial growth factor (VEGF), using polymerase chain reaction (PCR) restriction fragment length polymorphism assay and amplification refractory mutation system (ARMS) PCR. Haplotypes were predicted by Bayesian algorithm using the Phase program. RESULTS: All four polymorphisms were in Hardy-Weinberg equilibrium in both patients and controls. The frequency of the 936 T allele, which has been associated with lower production of VEGF, was significantly increased in RA patients compared with controls (22.7 vs 13.4%, P = 0.002). The frequencies of two haplotypes (CGCT and AAGT) which were predicted using the Phase program were significantly increased in RA patients compared with controls [33 vs 14%, odds ratio (OR) 2.636, 95% confidence interval (CI) 1.38-5.04 for CGCT; 17 vs 6%, OR 3.08, 95% CI 1.20-7.92 for AAGT]. The carriers of the susceptible haplotypes in RA patients had a younger age at disease onset but did not show a difference in the progression rate of radiographic joint destruction. CONCLUSIONS: Our data suggest that the VEGF gene may play a role in the development of RA

Rheumatoid arthritis associated with myelodysplastic syndrome: a case report.

Myelodysplastic syndromes (MDS) are a group of refractory anemias resulting from a clonal stem cell disorder often associated with cytogenetic abnormalities. There is increasing recognition of immunological abnormalities in patients with MDS, including defective B- and T-cell function, hyper- or hypogammaglobulinemia and monoclonal gammopathy. MDS have been associated with Sjögren's syndrome, polymyalgia rheumatica, relapsing polychondritis and systemic lupus erythematosus. Although there may be various rheumatologic features, including acute arthritis in MDS, chronic inflammatory arthritis is uncommonly combined. There have been a few reports that described cases of rheumatoid arthritis (RA) concurrent with MDS, but advanced rheumatoid arthritis with typical joint deformities has rarely been reported. We report a case of rheumatoid arthritis with atlantoaxial subluxation combined with refractory anemia in a 31-year-old woman.

Inhibition of interleukin-1beta converting enzyme family proteases (caspases) reduces cold injury-induced brain trauma and DNA fragmentation in mice.

The authors examined the effect of z-VAD.FMK, an inhibitor that blocks caspase family proteases, on cold injury-induced brain trauma, in which apoptosis as well as necrosis is assumed to play a role. A vehicle alone or with z-VAD.FMK was administered into the cerebral ventricles of mice 15 minutes before and 24 and 48 hours after cold injury. At 24 hours after cold injury, infarction volumes in the z-VAD.FMK-treated animals were significantly smaller than infarction volumes in the vehicle-treated animals, and were further decreased at 72 hours (0.92 +/- 1.80 mm3, z-VAD.FMK-treated animals; 7.46 +/- 3.53 mm3, vehicle-treated animals; mean +/- SD, n = 7 to 8). The amount of DNA fragmentation was significantly decreased in the z-VAD.FMK-treated animals compared with the vehicle-treated animals, as shown by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling staining and DNA gel electrophoresis. By Western blot analysis, both the proform and activated form of interleukin-1beta converting enzyme (caspase 1) were detected in the control brain, and the activated form showed moderate reduction after cold injury-induced brain trauma. These results indicate that caspase inhibitors could reduce cold injury-induced brain trauma by preventing neuronal cell death by DNA damage. The caspase family proteases appear to contribute to the mechanisms of cell death in cold injury-induced brain trauma and to provide therapeutic targets for traumatic brain injury.

Blood flow velocity changes in the middle cerebral artery as an index of the chronicity of hypertension.

This study was designed to demonstrate cerebral hemodynamic changes related to hypertension using transcranial Doppler ultrasonography. We measured the flow velocities and the Gosling pulsatility index of the middle cerebral artery and the internal carotid artery in 94 stroke-free, hypertensive patients and 81 age- and gender-matched healthy controls. Compared with the control subjects, patients with a longer duration (> or = 5 years) of hypertension showed significantly lower flow velocities of the middle cerebral artery and a higher Gosling pulsatility index of the middle cerebral- and the internal carotid artery. These differences were not observed in patients with a shorter duration of hypertension (<5 years). In the patient group, the mean velocity of the middle cerebral artery was significantly and inversely correlated with the duration of hypertension. Decreased flow velocity with increased pulsatility observed in this study suggest that alterations in the small cerebral vessels and arterioles contribute primarily to cerebral hemodynamic changes occurring in long-standing hypertension and also suggest the possible usefulness of transcranial Doppler in monitoring the progression of cerebral atherogenesis related to hypertension.

Gonadoblastoma and dysgerminoma associated with 46,XY pure gonadal dysgenesis--a case report.

Gonadoblastoma and dysgerminoma developed in a 24-year-old phenotypic female patient with 46,XY pure gonadal dysgenesis. This patient presented with primary amenorrhea. Clinical characteristics showed a typical stigmata of gonadal dysgenesis: primary amenorrhea, sexual infantilism, a small uterus and bilateral streak gonads. A 46,XY karyotype was made by lymphocyte culture. The patient was counseled to undergo a prophylactic bilateral gonadectomy, but she refused. Three years and three months after the initial diagnosis she felt a growing pelvic mass. Bilateral gonadectomy and total hysterectomy were performed. Histological examination revealed gonadoblastoma and dysgerminoma on both gonads. After surgery the patient received radiation therapy and also was started on hormone replacement therapy. Two years and two months after treatment by surgery the patient is well and free of recurrence.

Two cases of mitochondrial myopathy with predominant respiratory dysfunction.

Although it is well known that the respiratory failure is a major cause of death in most patients with chronic neuromuscular disease, predominant respiratory dysfunction without severe involvement of limb muscles is an unusual complication of mitochondrial myopathy in adult age. We experienced two cases of mitochondrial myopathy with severe involvement of respiratory function and only mild involvement of limb muscles. One is a 16 year old female and another is a 22 year old male. The diagnosis is based on morphologic characteristics of "ragged red fibers" under the light microscope and abnormal mitochondrias on the electron microscope in the muscle biopsy.