T1 Vertebra Pedicular Osteoid Osteoma: Minimally Invasive Surgical Resection Aided by New Integrated Navigation to 3D Imaging Device.

We hereby describe a minimally invasive resection of a T1 pedicular osteoid osteoma next to the vertebral canal. The patient had an 18-month report of painful radiculopathy. We performed the surgery under 3D imaging guidance using navigation with an all-in-one device. Full procedure irradiation was 1.17 mSv for a 181-picture acquisition. Complete operative time incision to closure was 58 minutes. Despite sparing the vertebral stability without any fixation, the tumor resection was well-margined, thanks to the focused guidance. After surgery, the patient had complete relief of his symptoms at the 6-month follow-up. 3D imaging system coupled to navigation made the procedure safe without consuming time. The single Surgivisio® device allows comfortable 3D minimally invasive spine navigation surgery with the ergonomics of a C-arm.

Intraoperative 2D C-arm and 3D O-arm in children: a comparative phantom study.

PURPOSE: Exposure to ionizing radiation is a concern for children during intraoperative imaging. We aimed to assess the radiation exposure to the paediatric patient with 2D and 3D imaging. METHODS: To evaluate the radiation exposure, patient absorbed doses to the organs were measured in an anthropomorphic phantom representing a five-year-old child, using thermoluminescent dosimeters. For comparative purposes, organ doses were measured using a C-arm for one minute of fluoroscopy and one acquisition with an O-arm. The cone-beam was centred on the pelvis. Direct and scattered irradiations were measured and compared (Student's t-test). Skin entrance dose rates were also evaluated. RESULTS: All radiation doses were expressed in µGy. Direct radiation doses of pelvic organs were between 631.22 and 1691.87 for the O-arm and between 214.08 and 737.51 for the C-arm, and were not significant (p = 0.07). Close scattered radiation on abdominal organs were between 25.11 and 114.85 for the O-arm and between 8.03 and 55.34 for the C-arm, and were not significant (p = 0.07). Far scattered radiation doses on thorax, neck and head varied from 0.86 to 6.42 for the O-arm and from 0.04 to 3.08 for the C-arm, and were significant (p = 0.02). The dose rate at the skin entrance was 328.58 µGy.s-1 for the O-arm and 1.90 with the C-arm. CONCLUSION: During imaging of the pelvis, absorbed doses for a 3D O-arm acquisition were higher than with one minute fluoroscopy with the C-arm. Further clinical studies comparing effective doses are needed to assess ionizing risks of the intraoperative imaging systems in children.

A Novel Minimally Invasive Reduction Technique by Balloon and Distractor for Intra-Articular Calcaneal Fractures: A Report of 2 Cases.

Treatment of displaced intra-articular fractures of the calcaneus remains a challenge for the orthopaedic surgeon. Conservative therapy is known to produce functional impairment. Surgical approach is plagued by soft-tissue complications and insufficient fracture reduction. We describe a minimally invasive technique that will hopefully improve these issues. We want to present our first experience through two cases. The first was a 46-year-old man who presented with a Sanders type IIBC calcaneal fracture, and the second was a 86-year-old woman with a type IIIBC calcaneal fracture. We introduced 2 Schanz screws in the talus and the calcaneus. After distraction, we introduced an inflatable balloon inside the calcaneus. By inflating the balloon, the articular surface was reduced by lifting it up. Then bone cement was injected in order to maintain the reduction. Additional screw fixation was used in the young patient. Postoperative imaging showed good congruence of the subtalar joint without leakage of cement, for the two cases. After 2 months, the patients had no pain and were without soft-tissue complications. We advocate this technique to perform a minimally invasive reduction and fixation of intra-articular calcaneal fractures because it preserves soft-tissues and provides good clinical results with early weight-bearing.

Cutaneous infection and bactaeremia caused by Erwinia billingiae: a case report.

Cellulitis and erysipelas are common skin infections usually caused by Staphylococcus aureus and streptococci. Gram-negative rods are rarely implicated. We report here a case of dermohypodermitis and bactaeremia caused by Erwinia billingiae, a Gram-negative bacteria usually pathogenic and epiphytic to pome fruit tree.

Effects of hydroxocobalamin on carboxyhemoglobin measured under physiologic and pathologic conditions.

CONTEXT: Pre-hospital administration of hydroxocobalamin (B12a) is used for empiric treatment of cyanide poisoning because cyanide poisoning is difficult to identify and requires immediate treatment. B12a interferes with the accuracy of several blood laboratory tests. This study aimed to explore how B12a affects carboxyhemoglobin (COHb) measurements in human blood at both physiologic and pathologic COHb levels. METHODS: Several clinically relevant concentrations of B12a were added to human blood samples containing physiologic (∼ 3%) and pathologic (30% and 50%) COHb levels. We then measured the COHb levels of the samples using two different co-oximeters, the Radiometer ABL 700 and the Rapidpoint 500, and compared to their actual baseline COHb levels. RESULTS: B12a had minimal effects on the COHb measured at both physiologic and pathologic levels when measured on the Radiometer. In contrast, the Rapidpoint B12a caused a dose-dependent decrease in the COHb measured, especially of pathologic COHb levels (∼ 30 and 50%). CONCLUSION: The magnitude of B12a interference on measured COHb is dependent upon the specific co-oximeter used, the actual COHb level and the serum B12a concentration. These errors may potentially influence clinical decision making and thus affect patient outcomes. Our findings emphasize the importance of measuring COHb levels on blood samples collected prior to B12a administration.

Nutritional status modulates behavioural and olfactory bulb Fos responses to isoamyl acetate or food odour in rats: roles of orexins and leptin.

Food odours are major determinants for food choice, and their detection depends on nutritional status. The effects of different odour stimuli on both behavioural responses (locomotor activity and sniffing) and Fos induction in olfactory bulbs (OB) were studied in satiated or 48-h fasted rats. We focused on two odour stimuli: isoamyl acetate (ISO), as a neutral stimulus either unknown or familiar, and food pellet odour, that were presented to quiet rats during the light phase of the day. We found significant effects of nutritional status and odour stimulus on both behavioural and OB responses. The locomotor activity induced by odour stimuli was always more marked in fasted than in satiated rats, and food odour induced increased sniffing activity only in fasted rats. Fos expression was quantified in periglomerular, mitral and granular OB cell layers. As a new odour, ISO induced a significant increase in Fos expression in all OB layers, similar in fasted and satiated rats. Significant OB responses to familiar odours were only observed in fasted rats. Among the numerous peptides shown to vary after 48 h of fasting, we focused on orexins (for which immunoreactive fibres are present in the OB) and leptin, as a peripheral hormone linked to adiposity, and tested their effects of food odour. The administration of orexin A in satiated animals partially mimicked fasting, since food odour increased OB Fos responses, but did not induce sniffing. The treatment of fasted animals with either an orexin receptors antagonist (ACT-078573) or leptin significantly decreased both locomotor activity, time spent sniffing food odour and OB Fos induction in all cell layers, thus mimicking a satiated status. We conclude that orexins and leptin are some of the factors that can modify behavioural and OB Fos responses to a familiar food odour.

Differential regulation of RGS-2 by constant and oscillating PTH concentrations.

PTH has diverse effects on bone metabolism: anabolic when given intermittently, catabolic when given continuously. The cellular mechanisms underlying the varying target cell response are not clear yet. PTH induces RGS-2, a member of the Regulator of G-protein Signaling protein family, via cAMP/PKA, and inactivates PKC-mediated signaling. To investigate intracellular signaling pathways with different PTH concentration-time patterns, we treated UMR 106-01 osteoblast-like cells in a perfusion system. PTH was administered intermittently (4 min/h, 10(-7) M) or continuously at an equivalent cumulative dose (6.6 x 10(-9) M). cAMP was measured using radioimmunoassay, mRNA levels using real-time rtPCR and ribonuclease protection assay, and protein levels using Western immunoblotting. A single PTH pulse transiently increased cAMP levels by 2000% +/- 1200%. In contrast to continuous PTH exposure, cAMP induction remained unchanged with intermittent PTH, ruling out desensitization of the PTH receptor. In continuously perfused cells, RGS-2 abundance was three to five times higher than in cells intermittently exposed to PTH for up to 12 h. MKP-1 and -3 were significantly less induced with pulsatile PTH; exposure-mode-dependent differences in MMP-13 and IGFBP-5 were small. Pulsatile but not continuous PTH administration prevents PTHrP receptor desensitization and accumulation of RGS-2 in osteoblasts, which should preserve PKC-dependent signaling.

Structural organization and biological relevance of oscillatory parathyroid hormone secretion.

Parathyroid gland secretory activity exhibits seasonal and circadian fluctuations, which are in synchrony with changes in serum calcium, phosphate, and bone turnover. In addition, an ultradian rhythm exists, which comprises seven pulses per hour, accounts for 30% of basal parathyroid hormone (PTH) release, and is highly sensitive to changes in ionized calcium. Acute hypocalcemia induces a selective, severalfold increase in pulse frequency and amplitude, whereas hypercalcemia suppresses the pulsatile secretion component, as does prolonged calcitriol therapy. Chronic renal failure is associated with a GFR dependent decrease in metabolic PTH clearance accounting for a two- to threefold increase in plasma PTH concentrations, a consistent increase of PTH burst mass and frequency, and a markedly reduced capacity to counteract changes in ionized calcium by modulation of pulsatile PTH release. Continuous PTH excess destroys bone, whereas intermittent administration of pharmacological doses of PTH improves bone morphology and strength in experimental and clinical settings. The molecular mechanisms of the exposure pattern dependent, contrasting biological effects of PTH may involve differential regulation of osteoblastic G protein signaling feedback circuits. In this context, calcimimetic and calcilytic agents are promising new therapeutic tools allowing for tight control of plasma PTH and restoration of circadian PTH rhythmicity.

[Surgical correction of fifth finger permanent abduction by tenodesis. Preliminary cadaver study]. / Correction chirurgicale de l'abduction permanente du cinquième doigt par ténodèse. Etude préliminaire cadavérique.

Permanent abduction of the little finger can be responsible for daily embarrassment in patients with an ulnar nerve palsy. To correct this deformity, active transfers are usually performed utilising the extensor tendons of the hand. Because of the anatomical variability of the extensor system of the hand, these active transfers can be responsible for postoperative loss of full extension of the little finger. Analysis of the orientation of the forces generated by these transfers shows that they are only weak adductors. A surgical technique using tenodesis is proposed in this preliminary study. This tenodesis has the objective of increasing the adductive forces on the little finger without an extensor tendon transfer. The advantages and disadvantages of this technique are discussed. A clinical evaluation will be undertaken at a later date to confirm the reliability of this technique.

Vitamin D and dexamethasone inversely regulate parathyroid hormone-induced regulator of G protein signaling-2 expression in osteoblast-like cells.

The PTH/PTHrP receptor stimulates both adenylate cyclase- and phospholipase C-dependent signaling pathways via different G proteins. The biological actions of PTH on bone are modified by steroid hormones. PTH induces expression of regulator of G protein signaling (RGS)-2, a putative preferential inhibitor of G(q)-mediated phospholipase C activation. We investigated whether steroid hormones interfere with PTH signaling by modulating PTH-induced RGS-2 expression in osteoblast-like UMR 106-01 cells. PTH (1-34) rapidly and transiently induced expression of RGS-2 mRNA and protein via the cAMP/protein kinase A pathway within 30 min, with maximal protein abundance after 2 h. PTH-induced RGS-2 preferentially bound to Galpha(q), compared with Galpha(s) protein. 1,25-(OH)(2)D(3) pretreatment enhanced PTH-induced RGS-2 mRNA and protein accumulation, whereas dexamethasone preincubation had an attenuating effect. These effects were due to modulation of the RGS-2 gene transcription rate, which increased by 35% with 1,25-(OH)(2)D(3) and decreased by 63% with dexamethasone pretreatment. RGS-2 mRNA half-life was not affected by either steroid. The transcriptional effects of dexamethasone and 1,25-(OH)(2)D(3) were independent of PTH/PTHrP receptor activation and were not explained by effects on cAMP accumulation, cAMP response element-binding protein expression or phosphorylation, or the abundance of the osteoblast-specific transcription factor core-binding factor alpha (CBFa1/Runx2), a known activator of RGS-2 expression. In conclusion, glucocorticoids and 1,25-(OH)(2)D(3) inversely modulate PTH-induced RGS-2 gene transcription. Regulation of RGS-2 may constitute a novel mechanism by which steroids modulate signaling via the PTH/PTHrP receptor and other G protein-coupled receptors in bone.

CD4 T cell recovery is slower in patients experiencing viral load rebounds during HAART.

To determine whether viral load rebounds during HAART impact on CD4+ T cell recovery and immune reconstitution, we studied a prospective cohort of 355 antiretroviral naive patients enrolled to be randomized in a trial of three strategies of induction/maintenance HAART. The extent of immune reconstitution in blood through 72 weeks of antiretroviral treatment was evaluated. Lymphocyte subset markers (CD4, CD8, CD45RA, CD62L, CD16, CD19), activation markers (HLA-DR, CD38, CD25) were performed by cytometry analysis. Our results showed that plasma HIV-1 RNA was suppressed to below 500 copies per ml through week 72 in 240 patients (group 1) while the remaining 115 patients experienced at least one viral rebound (group 2). At baseline, CD4 cell count was higher and HIV-1 RNA was lower in group 1 than in group 2. Over 72 weeks, mean increase in CD4+ T cell count was 0.32 cell/mm3/day in group 1 and only 0.14 cell/mm3/day in group 2 (P < 0.0001). However, the patterns of changes in CD4+ and CD8+ T cell subsets during therapy were very similar across the two groups with only subtle and very limited differences. We conclude that permanent control of HIV replication could be necessary for faster immune reconstitution.

Pedicle island flaps of latissimus dorsi. Applications in surgical repair of ruptures of the rotator cuff.

There are considerable problems in repair of major ruptures of the rotator cuff tendons particularly those of the supra and infraspinatus mm. The Gerber technique only transfers the tendinous insertion of the latissimus dorsi onto the greater tuberosity in massive cuff ruptures. We have extended this approach. In 12 shoulders, we studied the feasibility of a latissimus dorsi transfer harvested to fit and bearing muscle and tendon detached at its two extremities and transposed as a neurovascular island. The muscular part is transferred to the infra or supraspinous fossae and the tendon to the greater tuberosity with the aim of reactivating the infra and supraspinatus muscles. The lateral bundle of the latissimus dorsi is always transferable on its neurovascular pedicle into the infraspinous fossa, even into the supraspinous fossa, or into both if transfer is used as a bilobed flap. This anatomical work allowed a parallel study of the different possibilities of transposing the neurovascular pedicle, which might limit the technique, and also to determine the most appropriate surgical approach.

Amino acids and insulin are both required to regulate assembly of the eIF4E. eIF4G complex in rat skeletal muscle.

The respective roles of insulin and amino acids in regulation of skeletal muscle protein synthesis and degradation after feeding were examined in rats fasted for 17 h and refed over 1 h with either a 25 or a 0% amino acid/protein meal. In each nutritional condition, postprandial insulin secretion was either maintained (control groups: C(25) and C(0)) or blocked with diazoxide injections (diazoxide groups: DZ(25) and DZ(0)). Muscle protein metabolism was examined in vitro in epitrochlearis muscles. Only feeding the 25% amino acid/protein meal in the presence of increased plasma insulin concentration (C(25) group) stimulated protein synthesis and inhibited proteolysis in skeletal muscle compared with the postabsorptive state. The stimulation of protein synthesis was associated with increased phosphorylation of eukaryotic initiation factor (eIF)4E binding protein-1 (4E-BP1), reduced binding of eIF4E to 4E-BP1, and increased assembly of the active eIF4E. eIF4G complex. The p70 S6 kinase (p70(S6k)) was also hyperphosphorylated in response to the 25% amino acid/protein meal. Acute postprandial insulin deficiency induced by diazoxide injections totally abolished these effects. Feeding the 0% amino acid/protein meal with or without postprandial insulin deficiency did not stimulate muscle protein synthesis, reduce proteolysis, or regulate initiation factors and p70(S6k) compared with fasted rats. Taken together, our results suggest that both insulin and amino acids are required to stimulate protein synthesis, inhibit protein degradation, and regulate the interactions between eIF4E and 4E-BP1 or eIF4G in response to feeding.

Roles of the fructans from leaf sheaths and from the elongating leaf bases in the regrowth following defoliation of Lolium perenne L.

The study of carbohydrate metabolism in perennial ryegrass (Lolium perenne L. cv. Bravo) during the first 48 h of regrowth showed that fructans from elongating leaf bases were hydrolysed first whereas fructans in mature leaf sheaths were degraded only after a lag of 1.5 h. In elongating leaf bases, the decline in fructan content occurred not only in the differentiation zone (30-60 mm from the leaf base), but also in the growth zone. Unlike other soluble carbohydrates, the net deposition rate of fructose remained positive and even rose during the first day following defoliation. The activity of fructan exohydrolase (FEH; EC 3.2.1.80) was maximal in the differentiation zone before defoliation and increased in all segments, but peaked in the growth zone after defoliation. These data strongly indicate that fructans stored in the leaf growth zone were hydrolysed and recycled in that zone to sustain the refoliation immediately after defoliation. Despite the depletion of carbohydrates, leaves of defoliated plants elongated at a significantly higher rate than those of undefoliated plants, during the first 10 h of regrowth. This can be partly attributed to the transient increase in water and nitrate deposition rate. The results are discussed in relation to defoliation tolerance.

The interaction of glucocorticoids with the growth hormone-insulin-like growth factor axis and its effects on growth plate chondrocytes and bone cells.

Glucocorticosteroids interfere with the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis at different levels, and while low-dose corticosteroids may have permissive effects, high-dose, long-term treatment with corticosteroids may lead to growth disturbance. The mechanism involved is not clearly understood. The Janus kinase (JAK)-2/signal transducers and activators of transcription (STAT)-5 pathway is the means by which the corticosteroid interacts with the target-cell GH receptors. The production of local IGF-I is lowered by the corticosteroid via IGF-I transcription inhibition, and the rate of apoptosis is also increased, both in growth plate chondrocytes and osteoblast cell lines. GH in vitro and in vivo can partly counterbalance the negative effects of glucocorticoids on growth. GH has been seen to normalize growth rates in corticosteroid-treated rats as well as in children receiving glucocorticoids for immunosuppression following kidney transplantation.

Synergistic DNA damaging effects of 4-nitroquinoline-1-oxide and non-effective concentrations of methyl methanesulfonate in human fibroblasts.

DNA damage and DNA repair in human fibroblasts induced by the combination mixture of the genotoxic agents methyl methanesulfonate (MMS) and 4-nitroquinoline-1-oxide (4-NQO) were studied using the comet assay and the unscheduled DNA synthesis (UDS), respectively. Cells were simultaneously treated for 1h with the no observed effect concentration (noec) of MMS and increasing concentrations of 4-NQO or vice versa. Different results were obtained with the two types of mixtures. When the noec of 4-NQO was combined with increasing concentrations of MMS, no combination effects were observed. However, in experiments with increasing concentrations of 4-NQO and the noec of MMS, an increase in DNA damage and repair (and an enhancement of cytotoxicity) was demonstrated. Quantitative analysis of the effects by the isobologram method confirmed synergistic responses in both tests. We are proposing interactive actions between 4-NQO and MMS, whereby 4-NQO facilitates the attack of MMS on the DNA bases.

Evidence for linkage of a tandem duplication polymorphism upstream of the dopamine D4 receptor gene (DRD4) with attention deficit hyperactivity disorder (ADHD).

Attention deficit hyperactivity disorder (ADHD) is a common childhood-onset neurodevelopmental disorder. Evidence from twin, adoption, and family studies provide support for a genetic contribution to the etiology of ADHD. Several candidate gene studies have identified an association between a 7-repeat variant in exon 3 of the dopamine 4 receptor gene (DRD4) and ADHD. However, in spite of the positive reports finding association of the exon 3 VNTR with ADHD, several other polymorphisms within DRD4 have been identified that conceivably could contribute to risk for ADHD. Recently, another common polymorphism of the DRD4 gene has been described involving a 120-bp repeat element upstream of the 5' transcription initiation site. In this report, we describe results of analysis of the DRD4 120-bp repeat promoter polymorphism in a sample of 371 children with ADHD and their parents, using the transmission disequilibrium test (TDT). Results showed a significant preferential transmission of the 240-bp (long) allele with ADHD. Exploratory analyses of the Inattentive phenotypic subtype of ADHD strengthened the evidence for linkage. These data add further support for the role of DRD4 variants conferring increased risk for ADHD, and imply that additional studies of DRD4 and other related genes are needed.

Familial clustering of symptoms and disruptive behaviors in multiplex families with attention-deficit/hyperactivity disorder.

OBJECTIVE: To examine familial clustering of attention-deficit/hyperactivity disorder (ADHD), ADHD subtypes, symptoms, and oppositional behaviors in affected sibling pairs (ASPs) and their parents. METHOD: One hundred thirty-two ASPs, ranging in age from 5 to 25 years and ascertained through clinic and volunteer referrals, were examined for DSM-IV ADHD subtypes, oppositional defiant disorder (ODD), and conduct disorder (CD) with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL). Two hundred fifty-six parents in these families were assessed by means of the SADS-Lifetime version, Modified for the Study of Anxiety Disorders, Updated for DSM-IV (SADS-LA-IV), and the Behavioral Disorders supplement of the K-SADS-PL to determine ADHD, ODD, and CD. RESULTS: Fifty-five percent of families ascertained through an ASP have at least one parent with a lifetime diagnosis of ADHD. The frequency of ADHD in at least one parent was higher in families with at least one affected girl (63%) than in families with only affected boys (45%) (p = .02). There was no evidence that affected siblings or parents within ASP families showed similar patterns of ADHD symptoms, such as ADHD subtype classification. In contrast, CD significantly clustered in ASP families. CONCLUSIONS: The sex difference in prevalence of ADHD among ASPs is consistent with a model of inheritance in which girls require a greater loading of familial influences to develop ADHD. The lack of familial clustering of ADHD symptoms within ASP families suggests that hyperactive and inattentive symptoms reflect common familial underpinnings and not unique familial effects. In contrast, CD seems to reflect unique familial underpinnings distinct from those underlying ADHD.

Vineland Adaptive Behavior Scale scores as a function of age and initial IQ in 210 autistic children.

Human growth modeling statistics were utilized to examine how Vineland Adaptive Behavior Scale (VABS) scores changed in individuals with autistic disorder as a function of both age and initial IQ. Results revealed that subjects improved with age in all domains. The rate of growth in Communication and Daily Living Skills was related to initial IQ while rate of growth in Social Skills was not. Results should provide hope for parents and further support for the importance of functional social-communication skills in the treatment of autism.