Human herpesvirus 6 rhombencephalitis in immunocompetent children

This article describes the clinical presentation, diagnostic workup, and neurologic outcome of 3 immunocompetent pediatric patients diagnosed with human herpesvirus 6 (HHV6) rhombencephalitis. Presentation of HHV6 rhombencephalitis included new onset seizures, ataxia, encephalopathy, and opsoclonus-myoclonus. Neurologic examination revealed cranial neuropathies, cerebellar dysfunction, and extremity weakness. Magnetic resonance imaging abnormalities located in the cerebellum, basal ganglia/thalamus, and cerebral hemispheres were detected in 2 patients. Diagnosis of HHV6 encephalitis was made by real-time and nested polymerase chain reaction of serum and cerebrospinal fluid. The HHV6 variant A was detected in 2 patients by sequence analysis, and HHV6 protein was detected by immunomicroscopy in a patient who underwent biopsy secondary to progressive clinical and neuroradiographic findings. Therapy with intravenous ganciclovir did not correlate with resolution of neurologic symptoms, despite eventual non-detectable HHV6. Human herpesvirus 6 should be considered in the differential diagnosis of unexplained cases of rhombencephalitis in immunocompetent children. Features may be rapidly progressive and include profound encephalopathy, seizures, ataxia, and opsoclonus-myoclonus.     

Anatomic variants associated with peroneal tendon disorders: MR imaging findings in volunteers with asymptomatic ankles

PURPOSE: To evaluate prospectively, on magnetic resonance (MR) images in volunteers with asymptomatic ankles, various features of anatomic variants that are potentially associated with peroneal tendon disorders. MATERIALS AND METHODS: The study had institutional review board approval; informed consent was obtained from each volunteer. The prevalence of accessory peroneus quartus muscles, the location of the muscle-tendon junction of the peroneus brevis muscle, the prevalence and size of the peroneal tubercle and the retrotrochlear eminence, and the shape of the retromalleolar fibular groove were evaluated on MR images in 65 volunteers with asymptomatic ankles (35 women, 30 men; age range, 23-70 years; median age, 45 years). MR images were analyzed by two radiologists in consensus. The relationship between anatomic features and age and sex was analyzed by using Spearman rank correlation and the Wilcoxon rank sum test. RESULTS: A peroneus quartus muscle was identified in 11 (17%) ankles. Ninety percent of the musculotendinous junctions of the peroneus brevis muscle were located in a range between 27 mm proximal to and 13 mm distal to the fibular tip (median, 0 mm). A peroneal tubercle was identified in 36 (55%) ankles. Ninety percent of all peroneal tubercles were 4.6 mm or smaller (median height, 2.9 mm). A retrotrochlear eminence was seen in all ankles (median, 3.0 mm; 90% were 4.6 mm or smaller). The retromalleolar groove was concave in 18 (28%), flat in 28 (43%), convex in 12 (18%), and irregular in seven (11%) volunteers. A significant difference (P = .04) for the height of the retrotrochlear eminence was found between men (median, 3.4 mm) and women (median, 2.5 mm). All other P values were greater than .05. CONCLUSION: Anatomic variants thought to predispose individuals to peroneal tendon disorders can be seen in volunteers with asymptomatic ankles.     

Expressions of Topoisomerase IIα and BCRP in Metastatic Cells are Associated with Overall Survival in Small Cell Lung Cancer Patients

The aim of this study was to investigate the mRNA expression levels of multidrug resistance-associated proteins in chemo-na?ve metastatic lung cancer cells and to determine the correlation with response to chemotherapy and overall survival. Metastatic cells were obtained by transbronchial fine needle aspiration biopsy of enlarged mediastinal lymph nodes in 14 patients with small cell lung cancer (SCLC) and 7 patients with non-small cell lung cancer (NSCLC). After cytological confirmation of lung cancer type, total RNA was extracted from biopsy samples and reverse transcribed to cDNA, and real-time PCR for the genes of interest [P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), breast cancer resistance protein (BCRP), lung resistance protein (LRP) and topoisomerase IIα (TOPIIα)], was performed. We observed significantly decreased expression of BCRP and significantly increased expression of TOPIIα in metastatic SCLC cells compared to NSCLC. Furthermore, in SCLC high topoisomerase IIα and low BCRP expression levels positively correlated with longer overall survival. Our results showed higher expression levels of BCRP as well as lower levels of topoisomerase IIα in chemo-na?ve metastatic cells in NSCLC than in SCLC. These results correlate with previous observations that metastatic SCLC cells at the beginning of chemotherapy are potentially more sensitive to chemotherapeutic agents while in metastatic NSCLC cells resistance is usually inherent. We also showed that altered levels of topoisomerase IIα and BCRP in SCLC are important factors that contribute to resistance to chemotherapeutics that interfere with the enzyme and/or DNA and are highly associated with overall survival.     

PNUTS forms a trimeric protein complex with GABA(C) receptors and protein phosphatase 1

Phosphorylation and dephosphorylation of neurotransmitter receptors represent an important mechanism to regulate synaptic signal transduction. Here, we identified PNUTS, a targeting subunit of protein phosphatase 1 (PP1) as a new binding partner of GABA_C receptors. In the mammalian retina, PNUTS is co-expressed with GABA_C receptors and PP1 in bipolar cells. PNUTS and PP1 were detected in membrane protein preparations of the retina and precipitate with GABA_C receptor specific antibodies. Furthermore, PNUTS shuttles from the nucleus to the membrane in cells co-expressing GABA_C receptors. We show simultaneous binding of PP1 and GABA_C receptors to different domains of PNUTS, demonstrating that PNUTS cross-links PP1 and GABA_C receptors. Finally, modeling studies showed that the PP1 docking motif of PNUTS fits into the binding pocket on the enzyme surface, despite a C-terminal adjacent proline. We suggest that PNUTS targets PP1 to synaptic sites, acting as a temporary bridge between the phosphatase and GABA_C receptors.     

Flexor tendon injuries in pediatric patients

PURPOSE: The purpose of this research was to study the incidence and outcome of flexor tendon injuries in pediatric patients. METHODS: A survey of flexor tendon repair in children less than 16 years of age was performed in the City of Helsinki during 2000-2005. A retrospective clinical outcome study of all consecutive 28 patients with 45 involved fingers treated in Children's Hospital was also performed at a mean 38 months (range 12-53 months) after surgery. Active motion program after multistrand tendon repair was used in 33 fingers, cast immobilization in 11 fingers, and elastic bands in 1 finger. Functional and cosmetic subjective result was evaluated by a visual analog scale (VAS, 0-100). Range of motion (ROM) of metacarpophalangeal (MCP) and interphalangeal (IP) joints were measured. Grip strength was recorded. Functional outcome methods of Buck-Gramcko, ASSH, Strickland, and distal interphalangeal joint (DIP) ROM methods were applied. RESULTS: The calculated annual incidence of finger flexor injury per child in Helsinki was 0.036 per 1000. There were no ruptures of the multistrand repairs with active motion program, but three 2-strand core sutures failed within 1 month of the repair. Mean functional and cosmetic VAS scores (all 28 patients) were 87 and 84. Mean ROM ratio of the DIP joint in zone 1 and 2 injuries was 60%, compared to 98% in zone 3 and 5 injuries. Ranges of motion of the proximal interphalangeal (PIP) and MCP joints were practically normal in all patients. There was a discrepancy among the functional outcome scores, with good and excellent results in all 45 fingers (Buck-Gramcko), in 39 fingers (ASSH), in 36 fingers (original Strickland), and in 32 fingers (DIP ROM). CONCLUSIONS: Flexor tendon injuries in children are rare. Both subjective and objective outcomes are generally good. Active motion program is an effective technique after multistrand flexor tendon repair at all levels in children. Range of motion of the DIP joint may be a more effective means of evaluating outcome in pediatric flexor tendon injuries. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.     

Induced pluripotent stem cells for disease modeling,cell therapy and drug discovery in genetic autonomic disorders: a review

Clinical Autonomic Research - The autonomic nervous system (ANS) regulates all organs in the body independent of consciousness, and is thus essential for maintaining homeostasis of the entire...     

Randomized placebo-controlled study of oral calcium carbonate supplementation in plateletpheresis: II. Metabolic effects

BACKGROUND: The metabolic effects of oral calcium (Ca) supplementation during plateletpheresis were evaluated in a randomized, placebo-controlled trial. STUDY DESIGN AND METHODS: Twenty-three donors underwent four plateletpheresis procedures each, receiving in random order, elemental Ca (Ca) 1 or 2 g orally, or a corresponding placebo, 30 minutes before donation. Ten of these donors underwent a fifth procedure using a 4-g Ca dose. All procedures were performed at a fixed citrate infusion rate of 1.5 mg per kg per minute. RESULTS: Oral Ca induced dose-sensitive changes in parathyroid hormone (iPTH), total (tCa), and ionized (iCa) calcium levels. Compared to placebo, the greatest improvement in tCa and iCa levels occurred after the 2-g Ca dose (tCa of 73, 89, and 25% above placebo levels at 60 min, using 1, 2, and 4 g of oral Ca, respectively). Twenty-four hours after apheresis, serum tCa and iCa levels were higher, and iPTH levels lower, in donors who received oral Ca rather than placebo. Marked increases in urinary Ca and magnesium (Mg) excretion occurred at the completion of apheresis, were unaffected by Ca dose, and returned to baseline within 24 hours. Plateletpheresis also induced significant changes in serum alkaline phosphatase, 1,25-dihydroxyvitamin D, and osteocalcin levels immediately and at 24 hours after apheresis. CONCLUSION: Plateletpheresis induces marked acute metabolic effects, with sustained changes evident up to 24 hours after the completion of apheresis. Oral Ca supplementation exerts a significant but clinically modest impact on selected laboratory variables associated with these effects. Further studies are indicated to examine the long-term impact of plateletpheresis, with or without Ca supplementation, on donor Ca balance and bone density.