Administration of IL-18BP by gene therapy reduces inflammation and prevents joint destruction by downregulation of MMP-9 in rat AIA Role of MMP-9 in bone and joint destruction in arthritis

Background and objectives: Interleukin-18 (IL-18) is a pleiotropic cytokine involved in rheumatoid arthritis (RA) pathogenesis. This studywas carried out to evaluate the efficicacy of interleukin-18 binding protein (IL-18BP) gene therapy in the rat adjuvant-induced arthritis (AIA) model and to decipher the mechanisms by which IL-18BP delivery lessens bone destruction. Materials and methods: Arthritis was induced in female Lewis rat by Mycobacterium butyricum and the mRNA expression of IL-18 and IL-18BP was determined in the joints. In a preventative study, rats were divided into an adenovirus producing IL-18BP-Fc (AdmIL-18BP-Fc) group (n=8) and an adenovirus producing green fluorescent protein (AdGFP) group (n=7). On day 8 after AIA induction, adenoviruses were injected. Clinical parameters were assessed. At day 18, during maximal arthritis, the rats were euthanized, ankles were collected, and X-rays were performed. mRNA and protein were extracted from joints for analyses by qRT-PCR, multiplex, Western blot, and zymography. Results: We observed a decrease in the [IL-18BP/IL-18] ratio from day 7 to day 45. Administration of AdmIL-18BPd-Fc decreased clinical parameters and prevented bone and joint destruction compared to AdGFP administration. IL-18BP delivery reduced the metalloproteinase 9 (MMP-9) levels by 33% (at protein level (Fig. 1B) and functional level (Fig. 1C) and the tartrate-resistant acid phosphatase (TRAP) level by 44% (Fig. 1D) in the joint homogenates from AdmIL-18BPd-Fc compared to AdGFP treated rats.However, no variationwas observed forMMP-2 at the protein level (Fig.1A) and functional level (Fig. 1C). Conclusions: In rat AIA, a decrease in the [IL-18BP/ IL-18] ratio was observed. IL-18BP delivery prevented joint and bone destruction by downregulating MMP-9 and TRAP, suggesting a potential benefit of a similar therapy in RA.

Description of a pure seed fraction of oat through usual evaluations and radiographic images

The objective of this work was to evaluate the width and length incidence in a single seed fraction of oat [Avena sativa (L.)] cv. Cristal. The seeds were selected by a mechanical divider and by hand, and their correspondence to radiographic images in seeds with glumes and their caryopses. The width and length of the seeds with glumes and their caryopses were measured with electronic calliper, and their weight, with precision balance. Radiographic images of seeds with glumes were taken with an X-ray experimental equipment. The analyst selected seeds with glumes by the width and by the length previously determined and so with more weight, than that obtained by hand selection was slightly narrower, larger and lighter. The presence of the glumes masked the caryopses real dimensions (width and length), and conduced the analyst to select seeds that differed more by the width than by the length. The radiographic images showed the presence, or not, of caryopses inside the seed and its real dimensions. The mechanical partition method for seeds showed to be more efficient because the analyst subjectivity was not considered when the selection upon its dimensions was done. The X-ray analysis was a useful tool that complements the pure seed fraction selection as another factor of seed quality.

Nasopalatine duct cyst: report of 22 cases and review of the literature

Objectives: Nasopalatine duct cysts (NPDCs) are the most common developmental, epithelial and non-odontogenic cysts of the maxillae. The present study describes the clinicopathological characteristics of 22 NPDCs and discusses their etiology, incidence, treatment and prognosis, with a review of the literature on the subject. Study design: A retrospective observational study was made comprising a period of 36 years (1970-2006), and yielding a series of 22 patients with histopathological confirmation of NPDC. Surgical treatment was carried out under local anesthesia and comprised the dissection and removal of the cyst adopting a usually palatine approach, with the preparation of an enveloping flap from 1.4 to 2.4. Results: No statistically significant correlation was observed between the size of the lesion and patient age, although the size of the cyst differed according to patient gender, with a mean NPDC diameter of 16 mm in males and 12 mm in females. In no case did we observe root reabsorption or loss of vitality of the upper incisors following surgery. The X-ray image was rounded in 15 cases and heart-shaped in the remaining 7 cases. In the majority of cases panoramic X-rays and periapical and occlusal X-rays sufficed to identify the lesion, though computed tomography was used in cases of doubt. Conclusions: The etiology of NPDC is unclear. Simple surgical resection is recommended, followed by clinical and radiological control to ensure correct resolution of the case.

Apport du CT-3D dans le diagnostic et le traitement des fractures des plateaux tibiaux [Value of 3D CT in diagnosis and treatment of fractures of the tibial plateau]

A precise classification and an optimal understanding of tibial plateau fractures are the basis of a conservative treatment or adequate surgery. The aim of this prospective study is to determine the contribution of 3D CT to the classification of fractures (comparison with standard X-rays) and as an aid to the surgeon in preoperative planning and surgical reconstruction. Between November 1994 and July 1996, 20 patients presenting 22 tibial plateau fractures were considered in this study. They all underwent surgical treatment. The fractures were classified according to the Müller AO classification. They were all investigated by means of standard X-rays (AP, profile, oblique) and the 3D CT. Analysis of the results has shown the superiority of 3D CT in the planning (easier and more acute), in the classification (more precise), and in the exact assessment of the lesions (quantity of fragments); thereby proving to be of undeniable value of the surgeon.

Maladie d'Osgood-Schlatter [Osgood-Schlatter disease]

Osgood-Schlatter disease is a painful affection of the knee which touches particularly the active teenagers. Etiology of this frequent affection is unknown. This disease appears as an anterior knee pain and swelling started and worsened by the sports activities. Diagnosis is especially clinical. X-Rays, ultrasounds or IRM are not necessary for the diagnosis. Treatment is based on eviction of sports, analgesics and sometimes physiotherapy. Surgery is rarely proposed. Knee pain stops at the end of the growth. Long-term outcome is good for the majority of the patients. Some studies suggest a patella alta at the end of the growth, without an established correlation with knee arthritis.

Postmortem imaging: real or virtual?

Since the earliest years after the discovery of X-rays, radiological images have been used successfully for answering medico-legal and forensic questions. The possibility to evaluate the inside of a body without actually opening it has been appreciated and used in forensic pathology since then. However, the introduction of modern cross-sectional imaging techniques into post-mortem investigations has created controversial discussions among the medico-legal community. Terms like "Virtual Autopsy" and "Necro-Radiology" have led to confusion and controversy concerning the role of radiological techniques in forensic case work. Regardless, the use of those techniques in post-mortem investigations is increasing, especially the one of Muti-Detector Computed Tomography (MDCT). But also other imaging techniques such as Postmortem Angiography and Magnetic Resonance Imaging are increasingly applied. This presentation shall give an overview over the different techniques of postmortem imaging. It will critically explain their advantages and limitations in forensic death investigations compared to conventional autopsy. The role of postmortem imaging shall be discussed in order to distinguish between real state of the art and virtual reality.

Comparison of interferon-gamma release assay versus tuberculin skin test for tuberculosis screening in inflammatory bowel disease.

OBJECTIVES: Reactivation of latent tuberculosis (TB) in inflammatory bowel disease (IBD) patients treated with antitumor necrosis factor-alpha medication is a serious problem. Currently, TB screening includes chest x-rays and a tuberculin skin test (TST). The interferon-gamma release assay (IGRA) QuantiFERON-TB Gold In-Tube (QFT-G-IT) shows better specificity for diagnosing TB than the skin test. This study evaluates the two test methods among IBD patients. METHODS: Both TST and IGRA were performed on 212 subjects (114 Crohn's disease, 44 ulcerative colitis, 10 indeterminate colitis, 44 controls). RESULTS: Eighty-one percent of IBD patients were under immunosuppressive therapy; 71% of all subjects were vaccinated with Bacille Calmette Guérin; 18% of IBD patients and 43% of controls tested positive with the skin test (P < 0.0001). Vaccinated controls tested positive more often with the skin test (52%) than did vaccinated IBD patients (23%) (P = 0.011). Significantly fewer immunosuppressed patients tested positive with the skin test than did patients not receiving therapy (P = 0.007); 8% of patients tested positive with the QFT-G-IT test (14/168) compared to 9% (4/44) of controls. Test agreement was significantly higher in the controls (P = 0.044) compared to the IBD group. CONCLUSIONS: Agreement between the two test methods is poor in IBD patients. In contrast to the QFT-G-IT test, the TST is negatively influenced by immunosuppressive medication and vaccination status, and should thus be replaced by the IGRA for TB screening in immunosuppressed patients having IBD.

Post-traumatic overload or acute syndrome of the os trigonum: a possible cause of posterior ankle impingement.

The purpose of this paper is to discuss the post-traumatic overload syndrome of the os trigonum as a possible cause of posterior ankle impingement and hindfoot pain. We have reviewed 19 athletes who were referred to our foot unit between 1995 and 2001 because of posterior ankle pain, and in whom a post-traumatic overload syndrome of os trigonum was diagnosed. All these patients were followed up over a period of 2 years. In 11 cases a chronic repetitive movements in forced plantar flexion was found. In the other eight cases the pain appeared to persist after a standard treatment of an ankle sprain in inversion plantar flexion. The diagnosis was based on clinical history, physical examination and X-rays that revealed a non-fused os trigonum. The confirmation of diagnosis was carried-out injecting local anaesthetic under fluoroscopic control. In all cases a corticosteroid injection as first line treatment was performed. In 6 cases a second injection was necessary to alleviate pain because incomplete recovery with the first injection. Three cases (16%) were recalcitrant to this treatment and in these three cases a surgical excision of the os trigonum was carried out. Our conclusion is that after some chronic athletic activity or an acute ankle sprain the os trigonum, if present, may undergo mechanical overload, remain undisrupted and become painful. Treatment by corticosteroid injection often resolves the problem.

Nasopalatine duct cyst: report of 22 cases and review of the literature

Objectives: Nasopalatine duct cysts (NPDCs) are the most common developmental, epithelial and non-odontogenic cysts of the maxillae. The present study describes the clinicopathological characteristics of 22 NPDCs and discusses their etiology, incidence, treatment and prognosis, with a review of the literature on the subject. Study design: A retrospective observational study was made comprising a period of 36 years (1970-2006), and yielding a series of 22 patients with histopathological confirmation of NPDC. Surgical treatment was carried out under local anesthesia and comprised the dissection and removal of the cyst adopting a usually palatine approach, with the preparation of an enveloping flap from 1.4 to 2.4. Results: No statistically significant correlation was observed between the size of the lesion and patient age, although the size of the cyst differed according to patient gender, with a mean NPDC diameter of 16 mm in males and 12 mm in females. In no case did we observe root reabsorption or loss of vitality of the upper incisors following surgery. The X-ray image was rounded in 15 cases and heart-shaped in the remaining 7 cases. In the majority of cases panoramic X-rays and periapical and occlusal X-rays sufficed to identify the lesion, though computed tomography was used in cases of doubt. Conclusions: The etiology of NPDC is unclear. Simple surgical resection is recommended, followed by clinical and radiological control to ensure correct resolution of the case.

Pneumocystis-carinii-Pneumonie bei Säuglingen mit vertikaler HIV-Infektion in der Schweiz [Pneumocystis carinii pneumonia in infants with vertically acquired HIV infection in Switzerland]

OBJECTIVE: Review of incidence, clinical picture, therapy, and outcome of Pneumocystis carinii pneumonia (PCP) in infants with vertically-acquired HIV infection in Switzerland. METHODS: Inquiry among members of the Swiss Pediatrics AIDS Group, review of the data base of the Swiss Neonatal HIV Study and retrospective analysis of the charts from infants with PCP. RESULTS: Since 1986 PCP has been diagnosed in 10 out of 107 infants with vertically-acquired HIV infection. PCP occurred in 7 infants at the age of 3-6 months and in 3 at the age of 9-11 months. 4 infants showed symptoms related to HIV infection before developing PCP. Before the development of PCP, infection with HIV had been ascertained in 6 infants. In 2 the diagnosis was still unclear and in the 2 remaining the risk of HIV infection was not known. None of the infants was on primary prophylaxis against PCP. Signs and symptoms of PCP included cough and tachypnea (100%) as well as high fever up to 40 degrees C (90%). Transcutaneous oxygen saturation was 70-95%. Chest X-rays revealed interstitial infiltrates in 6 infants, localized infiltrates in 2 and interstitial as well as localized infiltrates in 2. The CD4+ cell count was, with one exception, < 1500/microliters, i.e. below the normal value for age. Side effects of high dose cotrimoxazole were noted in 6 patients. 5 infants required intubation and mechanical ventilation. 4 infants died due to PCP, including 3 of those who required intubation and mechanical ventilation. CONCLUSIONS: PCP in infants with vertically-acquired HIV infection preferentially occurs at the age of 3 to 6 months and is often lethal, especially in patients requiring intubation. Evaluation for HIV infection should be done as early as possible in order to introduce primary PCP prophylaxis in infants at risk for this opportunistic infection.

Revisiting spatial distribution and biochemical composition of calcium-containing crystals in human osteoarthritic articular cartilage.

INTRODUCTION: Calcium-containing (CaC) crystals, including basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP), are associated with destructive forms of osteoarthritis (OA). We assessed their distribution and biochemical and morphologic features in human knee OA cartilage. METHODS: We prospectively included 20 patients who underwent total knee replacement (TKR) for primary OA. CaC crystal characterization and identification involved Fourier-transform infra-red spectrometry and scanning electron microscopy of 8 to 10 cartilage zones of each knee, including medial and lateral femoral condyles and tibial plateaux and the intercondyle zone. Differential expression of genes involved in the mineralization process between cartilage with and without calcification was assessed in samples from 8 different patients by RT-PCR. Immunohistochemistry and histology studies were performed in 6 different patients. RESULTS: Mean (SEM) age and body mass index of patients at the time of TKR was 74.6 (1.7) years and 28.1 (1.6) kg/m², respectively. Preoperative X-rays showed joint calcifications (chondrocalcinosis) in 4 cases only. The medial femoro-tibial compartment was the most severely affected in all cases, and mean (SEM) Kellgren-Lawrence score was 3.8 (0.1). All 20 OA cartilages showed CaC crystals. The mineral content represented 7.7% (8.1%) of the cartilage weight. All patients showed BCP crystals, which were associated with CPP crystals for 8 joints. CaC crystals were present in all knee joint compartments and in a mean of 4.6 (1.7) of the 8 studied areas. Crystal content was similar between superficial and deep layers and between medial and femoral compartments. BCP samples showed spherical structures, typical of biological apatite, and CPP samples showed rod-shaped or cubic structures. The expression of several genes involved in mineralization, including human homolog of progressive ankylosis, plasma-cell-membrane glycoprotein 1 and tissue-nonspecific alkaline phosphatase, was upregulated in OA chondrocytes isolated from CaC crystal-containing cartilages. CONCLUSIONS: CaC crystal deposition is a widespread phenomenon in human OA articular cartilage involving the entire knee cartilage including macroscopically normal and less weight-bearing zones. Cartilage calcification is associated with altered expression of genes involved in the mineralisation process.

Les fractures du pilon tibial. Etude rétrospective à long terme de 51 fractures traitées par réduction sanglante et ostéosynthèse [Fractures of the tibial pilon. Long-term retrospective study of 51 fractures treated with open reduction and osteosynthesis].

PURPOSE OF THE STUDY: Fracture of the tibial pilon is a rare injury and its treatment remains difficult. The aim of this study was to report the complications and long term results of internal fixation using a technique which respects soft tissues and in which little material was used. MATERIAL: From 1985 to 1990, 48 patients with 51 fractures of the tibial pilon were treated by open reduction and internal fixation. All patients were submitted to a clinical and radiological review. METHODS: Both the Rüedi/Allgöwer and the AO-classification were used and determined by standard X-rays. Surgical procedure was performed with a 2 or 3 1/3 tube AO-plates and the peroneus was always fixed if fractured. Intraoperative reconstruction was analyzed. Subjective and objective scoring were used according to Olerud and Molander and the ankle arthritis was scored according to the classification determined by the SOFCOT in 1992. RESULTS: A minimal follow-up of 1 year for all cases was obtained, based on our own files. Thirty-eight patients (40 fractures) were evaluated after an average period of 88 months (56 to 124 months). Five patients developed cutaneous infection, three developed deep infection and four developed superficial skin necrosis. One aseptic non-union necessitated reoperation after 14 months. Two ankles had joint fusion after 19 and 25 months respectively due to severe arthritis. In six cases infectious and non-infectious complications led to surgical revision. According to the Olerud and Molander score, 15 per cent of the results were excellent, 45 per cent were good, 30 per cent were fair and 10 per cent poor. DISCUSSION: Literature shows a wide range of results following this surgical procedure. This is due to the difference in the type of trauma, classification system used, material used for the internal fixation and method of evaluation. The classification system of Rüedi and Allgöwer is the most commonly used but has a rather subjective tendency, especially between type II and type III. Treatment is difficult, especially for comminutive fractures associated with soft tissue damage. In this case, open reduction and internal fixation could increase iatrogenic lesions. For this reason surgical procedure can be delayed for several days, little material is used and soft tissue manipulation is reduced to minimum. In other study reports, the use of external fixation with or without minimal internal fixation have produced less complications without improving long term results. CONCLUSION: Analysis and comparison of study reports are difficult because of the absence of consensus in classification system and evaluation methods. The AO-classification, apparently the most objective, will probably be more and more used in the future. Treatment must be adapted to the bony lesion and soft tissue damage. Open reduction and internal fixation must be reserved for a specific group of lesion.

Goya's artwork imaging with Terahertz waves

In this paper we use a Terahertz (THz) time-domain system to image and analyze the structure of an artwork attributed to the Spanish artist Goya painted in 1771. The THz images show features that cannot be seen with optical inspection and complement data obtained with X-ray imaging that provide evidence of its authenticity, which is validated by other independent studies. For instance, a feature with a strong resemblance with one of Goya"s known signatures is seen in the THz images. In particular, this paper demonstrates the potential of THz imaging as a complementary technique along with X-ray for the verification and authentication of artwork pieces through the detection of features that remain hidden to optical inspection.

Exposure of the Swiss population by radiodiagnostics: 2003 review.

A nationwide investigation was conducted in Switzerland to establish the exposure of the population by medical x rays and update the results of the 1998 survey. Both the frequency and the dose variations were studied in order to determine the change in the collective dose. The frequency study addressed 206 general practitioners (GPs), 30 hospitals, and 10 private radiology institutes. Except for the latter, the response rate was very satisfactory. The dose study relied on the assessment of the speed class of the screen-film combinations used by the GPs as well as the results of two separate studies dedicated to fluoroscopy and CT. The investigation showed that the total number of all medical x-ray examinations performed by GPs registered a 1% decrease between 1998 and 2003, and that the sensitivities of the film-screen combinations registered a shift towards higher values, leading to a reduction of the dose delivered by a GP of the order of 20%. The study indicated also that the total number of all x-ray examinations performed in hospitals increased by 4%, with a slight increase of radiographies by 1% but significant decrease of examinations involving fluoroscopy (39%), and a 70% increase for CT examinations. Concerning the doses, the investigation of a selection of examinations involving fluoroscopy showed a significant increase of the kerma-area product (KAP) per procedure. For CT the study showed an increase of the dose-length product (DLP) per procedure for skull and abdomen examinations, and a decrease for chest examination. Both changes in the frequency and the effective dose per examination led to a 20% increase in the total collective dose.

A pilot study of the efficacy of IL1 blockade by anakinra in acute calcific periarthritis of the rotator cuff

Background/Purpose: Calcific periarthritis of rotator cuff can induce acute and severe shoulder pain and is accompnied by signs of acute inflammation. The calcific deposits are composed of calcium phosphate crystals such as hydroxyapatite or basic calcium phosphate. These crystals stimulate the production and release of IL1b from macrophages, in an analogous manner to MSU and CPPD crystals. As IL1 blockade is effective in reducing signs and symptoms of inflammation in acute gout, we performed a pilot study to study if it is also effective in calcific periarthritis Methods: 5 consecutive patients were included (mean age: 62, 3 females, 2 males) between March 2011 and March 2012. Symptoms of acute shoulder pain at rest had to be present for _7 days before inclusion, associated with limitation of shoulder mobility and the presence on calcification in the rotator cuff by conventional radiography. None of the patients had responded to at least 48 hours of high doses of NSAIDs. Exclusion criteria included no corticosteroid therapy in the last 2 weeks and the exclusion of other rheumatologic or infectious diseases- .Clinical evaluation consisted of patient assessment of pain (total, rest and activity) by VAS (100mm scale) at days 0, 1, 3, 15, 42 and clinical examination of shoulder mobility at days 0, 3, 15. ESR and CRP were measured at days 0, 3. Plain radiographs were performed at days 0 and 15 and an ultrasound examination (including Doppler) was performed at days 0, 3, 15. Anakinra 100mg daily was administered for 3 consecutive days after the first evaluation (day 0). Rescue analgesics were allowed and recorded. Results: At inclusion, all patients had severe shoulder pain: mean (SD) VAS day pain of 72mm (_25mm), mean VAS night pain of 96 (_ 5) and impaired shoulder mobility. CRP was elevated in all of them (mean of 3X). Treatment with anakinra lead to rapid relief of pain in all patients, starting already on the first night following the first injection. The reduction of VAS pain was particularly striking for rest pain: mean (SD) VAS of 4mm (_ 5) at day 1 and this response was maintained for the 5 patients at the end of the three injections without any need of rescue medication. Mean rest VAS was 6 (_8) at day 3. The effect on day pain was less spectacular: mean (SD) VAS at D1 of 30 (_ 18), at D3 of 27 (_ 11). Shoulder mobility also improved and the CRP normalized in 4 of 5 patients at day 3. At day 42, 4 of 5 the patients were still totally asymptomatic. On X rays and US, the calcifications were reduced in size: mean maximal diameter of 21 mm at day 0 to 12 mm at day 15, but did not disappear in any patient. The main change on US was a significant and rapid (at day 3) reduction of Doppler activity around the calcification. Conclusion: This pilot open study suggests that IL-1_ inhibition may be an interesting therapeutic approach in acute calcific periarthritis, especially in patients who have not responded adequately to NSAIDs. The effect on pain seems to be more rapid (within a few hours) than steroid injection although a randomized controlled study needs to be performed to confirm this observation.