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.

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.

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.

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.

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.

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.

Sympathetic innervation of the upper and lower regions of the uterus and cervix in the rat have different origins and routes.

The origins and routes of the postganglionic sympathetic nerve supply to the upper and lower uterus and to the cervix were investigated in the rat by using denervation procedures combined with immunohistochemistry and retrograde tracing. The sympathetic nerve fibers of the upper part of the uterus arise from the ovarian plexus nerve. They mainly originate (90%) from neurons of the suprarenal ganglia (SRG) and of the T10 to L3 ganglia of the paravertebral sympathetic chain. Fluoro-Gold injections into different regions of the upper uterus showed that the SRG neurons mainly provide innervation to the tubal extremity (52%) rather than to the uterine portion below this area (26%). Very few neurons of the celiac ganglion or the aorticorenal ganglia participated in this innervation. Most of the sympathetic innervation of the lower uterus and the cervix (90%) originates from neurons of the paravertebral ganglia T13 to S2, principally at the L2-L4 levels. By using immunocytochemistry, we show that very few tyrosine hydroxylase-positive neurons of the pelvic plexus project to these areas, where they represent only 3% of the sympathetic nerve supply. Again, very few neurons of the inferior mesenteric ganglion (IMG) supply the lower uterus and the cervix. The comparison between retrograde tracing experiments in intact animals and after the removal of the IMG shows that very few sympathetic postganglionic axons from the paravertebral chain pass through the IMG to reach the lower uterus and the cervix. In contrast, these axons mainly project to splanchnic nerves bypassing the IMG to connect with the hypogastric nerves. In addition, some axons supplying the lower uterus follow the superior vesical arteries and then reach the organ. Taken together, these results show that the upper region of the uterus receives a sympathetic innervation that is different in origin and route from that of the lower uterus and the cervix. Such a marked region-specific innervation suggests that nerve control of the myometrial activity may be functionally different between the oviduct and the cervical ends of the uterus.

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.

Small intensely fluorescent cells of the rat paracervical ganglion synthesize adrenaline, receive afferent innervation from postganglionic cholinergic neurones, and contain muscarinic receptors.

In the paracervical ganglion (PCG) of the rat, double-labelling immunofluorescence for catecholamine-synthesizing enzymes and HPLC measurement of catecholamine contents were first performed to evaluate whether intraganglionic small intensely fluorescent (SIF) cells are capable of synthesizing adrenaline. Immunolabelling for tyrosine hydroxylase (TH), dopamine beta-hydroxylase and phenylethanolamine-N-methyl transferase (PNMT) occurred in all SIF cells of the PCG, thus demonstrating the presence of all the enzymes required for adrenaline biosynthesis. Adrenaline levels were undetectable in the PCG but to test the hypothesis that PNMT is active in SIF cells, catecholamines were measured in ganglia of rats pretreated with pargyline, an inhibitor of the monoamine oxidase, the major enzyme involved in the catecholamine degradation. Pargyline treatment increased adrenaline levels in the PCG, thus demonstrating that SIF cells are capable of adrenaline synthesis. The undetectable levels of adrenaline in the PCG of untreated rats suggested a slow rate of biosynthesis of adrenaline in the ganglion. Furthermore, the use of double-labelling showed that SIF cells of the PCG were stained for muscarinic receptors and were approached by varicose ChAT-immunoreactive nerve fibres. Nerve fibres immunoreactive for ChAT were also observed associated with nerve cell bodies of ganglion neurones. Following deafferentation of the PCG, the ChAT-immunoreactive nerve fibres surrounding nerve cell bodies totally disappeared indicating their preganglionic origin, while those associated with SIF cells did not degenerate, which demonstrate that they derived from intraganglionic cholinergic neurones. Taken together, the results show that adrenaline may be a transmitter for SIF cells in the PCG and suggest that cholinergic neurones of the parasympathetic division of the PCG can modulate the SIF cell activity through the activation of muscarinic receptors.

Inhibition and habituation: preserved mechanisms of attentional selection in aging and Alzheimer's disease.

Are inhibition and habituation, processes that contribute to selective attention, impaired by aging or Alzheimer's disease (AD)? Younger adults, older adults, and adults with AD read lists of letters presented either alone or paired with distractor letters. Slower reading times for lists containing distractors relative to lists without distractors indexed concurrent interference (distraction). Slower reading times for lists in which distractors subsequently became targets relative to lists in which distractors and targets were unrelated indexed negative priming (inhibition). Faster reading times when distractors were constant in identity or location rather than random indexed repeated distractor effects (habituation). Distraction increased with aging and AD, whereas inhibition and habituation showed no age- or AD-related decline, suggesting that inhibition and habituation still function to aid attentional selection in older adults and adults with AD.

Peridural anesthesia disturbs maternal behavior in primiparous and multiparous parturient ewes.

Several experiments were carried out to study the effects of peridural anesthesia (Sylvocaine, 6 ml between sacrum and 1st caudal vertebra) performed either at the first signs of birth (early peridural: EP), or little before expulsion (late peridural: LP). When performed late, peridural anesthesia altered maternal behavior only slightly when compared with controls. By contrast severe deficits were observed in the case of EP. Seven out of 8 primiparae failed to show interest for their lamb within 30 min of the birth of the young (vs. 1/9 in LP group, p less than 0.01). In multiparae these proportions were 8/27 and 0/22 respectively (p less than 0.01). Within the EP group the effects of the peridural were more marked in primiparous than in multiparous mothers (p less than 0.05). Even in EP multiparous ewes becoming maternal within 5 min after giving birth a reduction in duration of licking was noted, when compared with the LP group (p less than 0.05). On the other hand, these same ewes established normally a selective bond within 2 hours after giving birth, as did the LP or control ewes. These results confirm the importance of genital stimulation for the rapid onset of maternal behavior in parturient ewes. They failed however to clarify the role played by genital stimulation in the establishment of a selective maternal bond.

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.

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.

Distribution of the various radiation-induced chromosomal rearrangements in relation to the dose and sampling time.

The quantitative analysis of the chromosome rearrangements detected in 2128 R-banded metaphases, obtained from gamma-irradiated human lymphocytes after 48 to 96 h in culture is reported. Depending on the culture time, and possibly on the dose of radiation (from 1 to 3 Gy), the most frequent type of rearrangement was either dicentrics or reciprocal translocations. In first generation mitoses, the frequency of cells without rearrangement ranged from 0.66 to 0.18, and the mean number of rearranged chromosomes per cell from 0.79 to 3.28. The dose-response curve follows a quadratic function for dicentric aberration yields, but not for other rearrangements.

Tentative estimate of the risk of chromosomal disease due to radiation-induced translocations in man.

An attempt to estimate one of the parameters establishing the risk of occurrence of abnormal live-born progeny by malsegregation of radiation-induced translocation is reported. A sample of 247 2-break translocations induced by gamma-rays in human lymphocytes was studied in relation to the minimal possible imbalance they could induce in gametogenesis. These imbalances were compared with chromosomal trisomies and monosomies known to be compatible with life after birth in man. It is concluded that at least 106 out of 247 translocations should not give viable products in cases of malsegregation. A second comparison, with translocations ascertained in human subjects for various reasons, led to the conclusion that about 2/5 of the radiation-induced translocations might involve a risk of partial trisomies or monosomies. Cell survival and frequency of meiotic malsegregations are other parameters needed to make a correct estimate. A short discussion shows the difficulty of such estimates from inter-specific comparisons.

Risk of chromosomal disease due to radiation. Tentative estimate from the study of radiation-induced translocations in human fibroblasts.

A sample of 214 reciprocal 2-break translocations observed in fibroblasts, both after accidental 'in vivo', and experimental 'in vitro' gamma-irradiation, was studied. The distribution of the breaks along the chromosomes does not seem at random. The minimal possible imbalance that these translocations could induce by malsegregation, if they existed in germ cells, was estimated. These imbalances were compared with the chromosomal trisomies and monosomies known to be compatible with life after birth in man. It is concluded that about 2/5 of the radiation-induced translocations might induce a viable trisomy and/or monosomy. This result, similar to that previously obtained in human lymphocytes, indicates the validity of the extrapolation from one tissue to another, and hopefully to germ cells.

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.

Effect of an inhibitor of prostaglandin synthesis on uterine motility in the ovariectomized ewe during induced oestrus. A preliminary report.

The myometrial electromyographic activity (EMG) of three ovariectomized ewes was studied after two consecutive treatments used for inducing oestrus: oestrogen administration and oestrogen plus an inhibitor of prostaglandin synthesis (indomethacin). The myometrial activity preceding treatments was used as a reference. The results of this study demonstrated that indomethacin modified the EMG of the myometrium recorded 24 hours after oestrogen injection. The rhythmic activity normally induced by oestrogens was suppressed, so that there was little or no difference between uterine activity recorded before and 24 hours after oestrogen injection.

[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.