INTRAVITREAL INJECTION OF AUTOLOGOUS BONE MARROW-DERIVED MONONUCLEAR CELLS FOR HEREDITARY RETINAL DYSTROPHY A Phase I Trial

Purpose: To evaluate the short-term (10 months) safety of a single intravitreal injection of autologous bone marrow-derived mononuclear cells in patients with retinitis pigmentosa or cone-rod dystrophy. Methods: A prospective, Phase I, nonrandomized, open-label study including 3 patients with retinitis pigmentosa and 2 patients with cone-rod dystrophy and an Early Treatment Diabetic Retinopathy Study best-corrected visual acuity of 20/200 or worse. Evaluations including best-corrected visual acuity, full-field electroretinography, kinetic visual field (Goldman), fluorescein and indocyanine green angiography, and optical coherence tomography were performed at baseline and 1, 7, 13, 18, 22, and 40 weeks after intravitreal injection of 10 X 10(6) autologous bone marrow-derived mononuclear cells (0.1 mL) into 1 study eye of each patient. Results: No adverse event associated with the injection was observed. A 1-line improvement in best-corrected visual acuity was measured in 4 patients 1 week after injection and was maintained throughout follow-up. Three patients showed undetectable electroretinography responses at all study visits, while 1 patient demonstrated residual responses for dark-adapted standard flash stimulus (a wave amplitude approximately 35 mu V), which remained recordable throughout follow-up, and 1 patient showed a small response (a wave amplitude approximately 20 mu V) recordable only at Weeks 7, 13, 22, and 40. Visual fields showed no reduction (with a Goldman Standard V5e stimulus) for any patient at any visit. No other changes were observed on optical coherence tomography or fluorescein and indocyanine green angiograms. Conclusion: Intravitreal injection of autologous bone marrow-derived mononuclear cells in eyes with advanced retinitis pigmentosa or cone-rod dystrophy was associated with no detectable structural or functional toxicity over a period of 10 months. Further studies are required to investigate the role, if any, of autologous bone marrow-derived mononuclear cell therapy in the management of retinal dystrophies. RETINA 31: 1207-1214, 2011

Methotrexate Withdrawal at 6 vs 12 Months in Juvenile Idiopathic Arthritis in Remission A Randomized Clinical Trial

Context Novel therapies have improved the remission rate in chronic inflammatory disorders including juvenile idiopathic arthritis (JIA). Therefore, strategies of tapering therapy and reliable parameters for detecting subclinical inflammation have now become challenging questions. Objectives To analyze whether longer methotrexate treatment during remission of JIA prevents flares after withdrawal of medication and whether specific biomarkers identify patients at risk for flares. Design, Setting, and Patients Prospective, open, multicenter, medication-withdrawal randomized clinical trial including 364 patients (median age, 11.0 years) with JIA recruited in 61 centers from 29 countries between February 2005 and June 2006. Patients were included at first confirmation of clinical remission while continuing medication. At the time of therapy withdrawal, levels of the phagocyte activation marker myeloid-related proteins 8 and 14 heterocomplex (MRP8/14) were determined. Intervention Patients were randomly assigned to continue with methotrexate therapy for either 6 months (group 1 [n = 183]) or 12 months (group 2 [n = 181]) after induction of disease remission. Main Outcome Measures Primary outcome was relapse rate in the 2 treatment groups; secondary outcome was time to relapse. In a prespecified cohort analysis, the prognostic accuracy of MRP8/14 concentrations for the risk of flares was assessed. Results Intention-to-treat analysis of the primary outcome revealed relapse within 24 months after the inclusion into the study in 98 of 183 patients (relapse rate, 56.7%) in group 1 and 94 of 181 (55.6%) in group 2. The odds ratio for group 1 vs group 2 was 1.02 (95% CI, 0.82-1.27; P=.86). The median relapse-free interval after inclusion was 21.0 months in group 1 and 23.0 months in group 2. The hazard ratio for group 1 vs group 2 was 1.07 (95% CI, 0.82-1.41; P=.61). Median follow-up duration after inclusion was 34.2 and 34.3 months in groups 1 and 2, respectively. Levels of MRP8/14 during remission were significantly higher in patients who subsequently developed flares (median, 715 [IQR, 320-1110] ng/mL) compared with patients maintaining stable remission (400 [IQR, 220-800] ng/mL; P=.003). Low MRP8/14 levels indicated a low risk of flares within the next 3 months following the biomarker test (area under the receiver operating characteristic curve, 0.76; 95% CI, 0.62-0.90). Conclusions In patients with JIA in remission, a 12-month vs 6-month withdrawal of methotrexate did not reduce the relapse rate. Higher MRP8/14 concentrations were associated with risk of relapse after discontinuing methotrexate.

Neuroprotective effects of oral lamotrigine administration on rabbit retinas after pars plana vitrectomy and silicone oil injection

Purpose: To investigate potential retinal neuroprotective effects of oral lamotrigine in rabbits after pars plana vitrectomy (PPV) and intravitreal silicone oil injection (SOI). Methods: Twelve New Zealand rabbits (weight, 2.0-2.5 kg) underwent PPV with SOI on the right eye. For 30 days postoperatively, 6 rabbits received a daily oral dose of lamotrigine (25 mg/kg), and 6 rabbits received a daily oral dose of water. The animals were killed 30 days after surgery. All retinas were processed histologically, immunostained using glial fibrillary acidic protein (GFAP), and analyzed by fluorescence microscopy. Retina sections from all groups were analyzed by TUNEL for the presence of apoptosis and stained with hematoxylin-eosin for morphologic analysis and retina cell density measurements in each layer using a Zeiss Axiophot microscope and KS 400 software. Results: Retinas from water-operated eyes showed a significant decrease in cell density associated with cell death compared with retinas from water-control eyes; cell density was reduced by 56% in the outer nuclear layer (ONL), 49% in the inner nuclear layer (INL), and 64% in the ganglion cell layer (GCL). Lamotrigine-operated retinas showed a reduction in cell death when compared with water-operated retinas; cell death was reduced by 52% in the ONL, 25% in the INL, and 56% in the GCL. Water-operated retinas showed TUNEL-positive cells and GFAP immunofluorescence throughout Muller cell processes; lamotrigine-operated retinas showed no TUNEL-positive cells and decreased GFAP staining when compared with water-operated retinas. Conclusions: PPV with SOI was associated with apoptosis of retinal cells and activation of glial cells in rabbit eyes. Oral lamotrigine administration provided protection against these effects.

Treatment of Brain Arteriovenous Malformations by Double Arterial Catheterization with Simultaneous Injection of Onyx: Retrospective Series of 17 Patients

BACKGROUND AND PURPOSE: The use of Onyx in the treatment of intracranial AVMs has increased the cure rate of endovascular embolization compared with the use of liquid adhesive agents. Inadvertent occlusion of the draining veins before the complete exclusion of the nidus constitutes a major risk of bleeding. We report a case series using the technique of double simultaneous arterial catheterization as an approach to achieve the complete, exclusion of the nidus before reaching the venous drainage, through a more controlled hemodynamic filling. MATERIALS AND METHODS: Between April 2008 and November 2009, 17 patients with brain AVMs were treated by the DACT. The mean age of the patients was 32.7 years (range, 6-54 years), with 9 females and 8 males. The clinical onset was characterized by intracranial hemorrhage in 8 patients and by seizures in 7. The size of the AVMs ranged from 13 to 54 mm (average, 26.2 mm). The DACT was always used with the objective of curing the AVM. RESULTS: All 17 patients completed the EVT. The average number of sessions conducted was 1.4 (range, 1-3 sessions), with the average injection amount of 6.9 mL of Onyx (range, 2-25.2 mL). Sixteen AVMs (94.1%) were angiographically cured by embolization. Clinical complications occurred in 2 patients (11.7%); 1 of these was permanent (5.9%). No deaths were registered. CONCLUSIONS: This preliminary series shows that the DACT presents satisfactory results when used with curative intent.

Feline injection-site sarcoma

The feline injection-site sarcoma (FIS) is a challenge for the veterinarian and the affected cat`s owner. The injectable applications (vaccines, medications) seems to be the reason for that neoplasia, more specifically, the inflammation caused by injury of given drugs or antigens to the health tissue. Generally the FIS presents a more aggressive behavior when compared to sarcoma not associated to application. The most effective treatment his not been established yet, but it is believed that a multimodality of therapies, surgery, radiotherapy, and chemotherapy would be the most indicated option. The knowledge of the illness in all of its aspects will Supply to professionals colleges subsidies in relation to the best way to approach its diagnosis and treatment.

Tc-99m-labeled dextran for mammary lymphoscintigraphy in dogs

Lymphoscintigraphy is the technique of choice for sentinel lymph node detection in women with early breast cancer, but there is limited information evaluating the value of this technique in animals. We investigated mammary lymphatic drainage in 25 young female mongrel dogs by intramammary injection of 18.5 MBq of Tc-99m-dextran (70,000 Da). Lymph node anatomical referencing was obtained using an external marker, bone scintigraphy, or scintiscanning the body contour. Cranial and caudal thoracic mammary glands drained into the cranial sternal lymph node and axillary lymph center. The cranial thoracic mammary gland also drained into the superficial cervical lymph node in two of five animals. The cranial abdominal gland was drained by the axillary lymph center. The caudal abdominal mammary gland was drained by the superficial inguinal lymph node in all animals and simultaneously by medial iliac lymph nodes in four of five animals. In one dog, this mammary gland was also drained by the mediastinal and the superficial cervical lymph nodes. The inguinal mammary gland was drained by superficial inguinal lymph nodes and simultaneously via the medial iliac lymph node in one animal. Lymphatic communications between lymph nodes were identified in 11 of 25 (44%) animals. Tc-99m-dextran mammary lymphoscintigraphy was easy and rapid to perform and may provide valuable information for further studies.

Central effects of Tityus serrulatus and Tityus bahiensis scorpion venoms after intraperitoneal injection in rats

A great number of studies on scorpion venoms associate their effects to the autonomic nervous system, and few data are available about their action on the central nervous system (CNS). The aim of this work was to evaluate some central effects after intraperitoneal injection of Tityus serrulatus or T. bahiensis scorpion venoms. The hippocampal concentration of some neurotransmitters and their metabolites were determined. Electroencephalographic and behavioral observations were performed, and all brains were removed for histopathological analysis of hippocampal areas. Both venoms induced electrographic and behavioral alterations despite T bahiensis venom affects less the electrographic activity than T. serrulatus venom. Neurochemical analysis demonstrated no alteration in the extracellular levels of almost all the neurotransmitters evaluated, at least in the hippocampus, and no neuronal loss in this area was observed. Meanwhile, extracellular concentration of HVA increased up to 10 times in approximately 1/3 of the animals of both groups. Scorpion venoms seem to exert a small but important central effect. More studies in this field are necessary because they may be useful in developing new strategies to reduce the damage caused by scorpion stings. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Effects of gonadotropin-releasing hormone at initiation of the 5-d timed artificial insemination (AI) program and timing of induction of ovulation relative to AI on ovarian dynamics and fertility of dairy heifers

Two experiments evaluated the effects of the first GnRH injection of the 5-d timed artificial insemination (AI) program on ovarian responses and pregnancy per AT (P/AI), and the effect of timing of the final GnRH to induce ovulation relative to AT on P/AI. In experiment 1, 605 Holstein heifers were synchronized for their second insemination and assigned randomly to receive GnRH on study d 0 (n = 298) or to remain as untreated controls (n = 307). Ovaries were scanned on study d 0 and 5. All heifers received a controlled internal drug-release (CIDR) insert containing progesterone on d 0, a single injection of PGF(2 alpha),, and removal of the CIDR on d 5, and GnRH concurrent with timed AT on d 8. Blood was analyzed for progesterone at AI. Pregnancy was diagnosed on d 32 and 60 after AI. Ovulation on study d 0 was greater for GnRH than control (35.4 vs. 10.6%). Presence of a new corpus luteum (CL) at PGF(2 alpha),, injection was greater for GnRH than for control (43.1 vs. 20.8%), although the proportion of heifers with a CL at PGF(2 alpha) did not differ between treatments and averaged 87.1%. Progesterone on the day of AT was greater for GaRH than control (0.50 +/- 0.07 vs. 0.28 +/- 0.07 ng/mL). The proportion of heifers at AI with progesterone <0.5 ng/mL was less for GURH than for control (73.8 vs. 88.2%). The proportion of heifers in estrus at AI did not differ between treatments and averaged 66.8%. Pregnancy per AI was not affected by treatment at d 32 or 60 (GnRH = 52.5 and 49.8% vs. control = 54.1 and 50.0%), and pregnancy loss averaged 6.0%. Responses to GnRH were not influenced by ovarian status on study d 0. In experiment 2, 1,295 heifers were synchronized for their first insemination and assigned randomly to receive a CIDR on d 0, PGF(2 alpha) and removal of the CIDR on d 5, and either GnRH 56 h after PGF(2 alpha) and AI 16 h later (OVS56, n = 644) or GnRH concurrent with AI 72 h after PGF(2 alpha) (COS72; n = 651). Estrus at AI was greater for COS72 than for OVS56 (61.4 vs. 47.5). Treatment did not affect P/AI on d 32 in heifers displaying signs of estrus at AI, but COS72 improved P/AI compared with OVS56 (55.0 vs. 47.6%) in those not in estrus at AI. Similarly, P/AI on d 60 did not differ between treatments for heifers displaying estrus, but COS72 improved P/AI compared with OVS56 (53.0 vs. 44.7%) in those not in estrus at AI. Administration of GnRH on the first day of the 5-d timed AI program resulted in low ovulation rate and no improvement in P/AI when heifers received a single PGF(2 alpha) injection 5 d later. Moreover, extending the proestrus by delaying the finAI GnRH from 56 to 72 h concurrent with AI benefited fertility of dairy heifers that did not display signs of estrus at insemination following the 5-d timed AI protocol.

Behavioural responses of heifers to ACTH injections

The objective of this study was to investigate behavioural changes in Holstein heifers caused by exogenous adrenocorticotropic hormone (ACTH) administration. Twelve 11-month-old heifers were submitted to either a single saline or ACTH injection and then the treatments were switched after 3 days (n = 12 heifers/treatment). Heifers were in full view throughout the experimental period and recordings started immediately after ACTH and saline administration (injection corresponded to time 0 min), with general activity patterns of each heifer recorded on videotape for 24 h. Behavioural results during the first two experimental hours showed that heifers were less active and spent more time lying following ACTH than after saline treatment (P = 0.04). Also, heifers spent significantly less time ruminating immediately following ACTH injection (P = 0.05). However, feed intake measured after 4 and 24 h was similar between treatments (P > 0.05). Overall, there was no significant influence of ACTH treatment on frequency or duration of behaviours during the 4- and 24-h periods following injection (P > 0.05). The rapid and minimal effect of ACTH injection on behaviour suggests that peripheral administration of ACTH can be used to measure reactivity of the adrenal cortex without inducing biologically significant consequences. (C) 2010 Elsevier B.V. All rights reserved.

Gingival and bone necrosis caused by accidental sodium hypochlorite injection instead of anaesthetic solution

Aim To report clinical complications (pain, necrotic gingival tissue and bone sequestration) resulting from accidental injection of sodium hypochlorite. Summary Root canal treatment is a routine clinical procedure with few reported complications. Sodium hypochlorite (NaOCl) is commonly used as an irrigant during the procedure because of its tissue-dissolving, antibacterial and lubricating properties. This paper presents a case in which accidental injection of sodium hypochlorite into the lingual gingiva of a female patient caused gingival and bone necrosis. Surgical intervention was required. Key learning points Sodium hypochlorite is dangerous if injected into the tissues. The presentation of sodium hypochlorite in glass, anaesthetic type cartridges is potentially dangerous, and should be condemned. All healthcare workers should check carefully the contents of any syringe before injecting into patients.

Quantitative analysis of Langerhans` cells in oral chronic graft-vs.-host disease

The Langerhans cells (LCs) are scattered throughout the epithelium of skin and mucosa and have been associated with the graft-vs.-host disease (GVHD), which is the highest cause of morbidity and mortality in patients who underwent bone marrow transplant (BMT). This study aims at quantifying the LCs in the oral chronic GVHD (cGVHD). Microscopic sections from biopsies carried out in the buccal mucosa of 40 patients who underwent allogenic BMT and developed (20) or not (20) oral cGVHD (Groups 1 and 2, respectively) were utilised. For the control group, free surgical margins of 20 biopsies of non-inflammatory lesions in the buccal mucosa (Group 3) were used. The sections were studied in routine colouration and immunostained for CD1a. Group 1 (with cGVHD) presented a greater number of Langerhans` cells/mm(2) (50.6 +/- 37.2) when compared with the other groups (Group 2, 23.11 +/- 19.7; Group 3, 16.6 +/- 17.3). Our results suggest a greater recruitment of LCs in patients transplanted with cGVHD, probably as a result of cytokines secreted by the inflammatory cells.

Influence of rapid palatal expansion on maxillary incisor alignment stability

Introduction: The purpose of this retrospective study was to compare the long-term stability of maxillary incisor alignment in patients treated with and without rapid maxillary expansion (RME). Methods: The sample comprised 48 subjects with Class I and Class II malocclusions, treated without extractions with fixed edgewise appliances, divided into 2 groups according to the treatment protocol: group 1 comprised 25 patients (15 girls, 10 boys) at a mean initial age of 13.53 years (SD, 1.63), who had RME during orthodontic treatment. Group 2 comprised 23 patients (13 girls, 10 boys) at a mean initial age of 13.36 years (SD, 1.81 years), treated with fixed appliances without RME. Maxillary dental cast measurements were obtained at the pretreatment, posttreatment, and long-term posttreatment stages. Variables assessed were the irregularity index and maxillary arch dimensions. Intergroup comparisons were made with independent t tests. Results: Greater transverse increases were found during treatment in the group treated with RME. However, during the long-term posttreatment period, no significant difference was observed in the amount of incisor crowding relapse between the groups. Conclusions: RME did not influence long-term maxillary anterior alignment stability. (Am J Orthod Dentofacial Orthop 2010; 137: 164. e1-164.e6)

Effects of Orthopedic Rapid Maxillary Expansion on Internal Nasal Dimensions in Children With Cleft Lip and Palate Assessed by Acoustic Rhinometry

The objective of the current study was to characterize the internal nasal dimensions of children with repaired cleft lip and palate and transverse maxillary deficiency, using acoustic rhinometry and analyze the changes caused by rapid maxillary expansion (RME). A convenience sampling of 19 cleft lip and palate individuals, aged 14 to 18 years, of both sexes, previously submitted to primary surgeries and referred for RME were analyzed prospectively at the Hospital for Rehabilitation of Craniofacial Anomalies, University of Sao Paulo, Bauru, Sao Paulo, Brazil. All patients underwent acoustic rhinometry before installation of the expansor and at 30 and 180 days after the active expansion phase. Nasal cross-sectional areas and volumes corresponding to the nasal valve (CSA(1) and V(1)) and the turbinates (CSA(2), CSA(3), and V(2)) regions were determined before and after nasal decongestion. Rapid maxillary expansion led to a statistically significant increase (P < 0.05) in mean CSA(1), CSA(2), V(1), and V(2) (without nasal decongestion) and in CSA(1) and V(1) (with decongestion) in the group as a whole. Individual data analysis showed that 58% of the patients responded positively to RME, with an average increase in CSA(1) of 26% (with decongestion), whereas 37% of the patients had no significant change. Only 1 patient (5%) showed a decrease. The findings contribute toward the characterization of nasal deformities determined by the cleft and demonstrate the positive effect RME had on nasal morphophysiology in a significant number of the patients who underwent this procedure.

Resin cement thickness in oval-shaped canals: Oval vs. circular fiber posts in combination with different tips/drills for post space preparation

Purpose: To evaluate the cement thickness around oval and circular posts luted in oval post spaces prepared with different drills/tips. Methods: Extracted premolars were endodontically treated and obturated, then randomly divided into three groups (n = 5) according to the tips/drills used for post-space preparation and to the type of fiber post luted: medium grit oval tip + oval posts, fine grit oval tip + oval posts, Mtwo Post File drill + circular posts. The specimens were sectioned in horizontal slices; one slice per canal third was chosen for each post-space, resulting in three slices for each specimen. The distances between the canal wall and the post perimeter were measured on SEM images of each slice. Results: The fine grit tip + oval post group obtained statistically significant lower cement thicknesses than the other groups (P < 0.05), in particular in the apical third. The MtwoPF + circular post group showed the highest cement thickness, comparable to that of the medium tip + oval post group. A good post fitting in oval-shaped canals can be obtained using a fine grit oval tip combined with oval posts. (Am J Dent 2009;22:290-294).

Intralesional injection of triamcinolone hexacetonide as an alternative treatment for central giant-cell granuloma in 21 cases

Central giant-cell granulomas are benign, but occasionally aggressive, lesions that traditionally have been treated surgically. 21 cases of central giant-cell granuloma of the jaw were treated with intralesional injection of corticosteroids. The treatment protocol adopted was intralesional injection of 20 mg/ml triamcinolone hexacetonide diluted in an anaesthetic solution of 2% lidocaine/epinephrine 1:200,000 in the proportion 1:1; 1.0 ml of the solution was infiltrated for every 1 cm(3) of radiolucid area of the lesion, totalling 6 biweekly applications. Ten patients had aggressive lesions and 11 nonaggressive. Two patients showed a negative response to the treatment and underwent surgical resection, 4 showed a moderate response and 15 a good response. 8 of the 19 who had a moderate-to-good response to the drug treatment underwent osteoplasty to reestablish facial aesthetics. In these cases, only mature or dysplastic bone was observed, with the presence or absence of rare giant multinucleated cells. The advantages of this therapy are its less-invasive nature, the probable lower cost to the patient, lower risk and the ability to treat the lesion surgically in the future, if necessary.