Synovial chemokine expression and relationship with knee symptoms in patients with meniscal tears.

OBJECTIVE: In patients with knee OA, synovitis is associated with knee pain and symptoms. We previously identified synovial mRNA expression of a set of chemokines (CCL19, IL-8, CCL5, XCL-1, CCR7) associated with synovitis in patients with meniscal tears but without radiographic OA. CCL19 and CCR7 were also associated with knee symptoms. This study sought to validate expression of these chemokines and association with knee symptoms in more typical patients presenting for meniscal arthroscopy, many who have pre-existing OA. DESIGN: Synovial fluid (SF) and biopsies were collected from patients undergoing meniscal arthroscopy. Synovial mRNA expression was measured using quantitative RT-PCR. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was administered preoperatively. Regression analyses determined if associations between chemokine mRNA levels and KOOS scores were independent of other factors including radiographic OA. CCL19 in SF was measured by ELISA, and compared to patients with advanced knee OA and asymptomatic organ donors. RESULTS: 90% of patients had intra-operative evidence of early cartilage degeneration. CCL19, IL-8, CCL5, XCL1, CCR7 transcripts were detected in all patients. Synovial CCL19 mRNA levels independently correlated with KOOS Activities of Daily Living (ADL) scores (95% CI [-8.071, -0.331], P = 0.036), indicating higher expression was associated with more knee-related dysfunction. SF CCL19 was detected in 7 of 10 patients, compared to 4 of 10 asymptomatic donors. CONCLUSION: In typical patients presenting for meniscal arthroscopy, synovial CCL19 mRNA expression was associated with knee-related difficulty with ADL, independent of other factors including presence of radiographic knee OA.

Transport distraction osteogenesis for closing full-thickness calvarial defects in sheep.

OBJECTIVE: To prove the hypothesis that transport distraction osteogenesis can be applied to the skull to close critical-size calvarial defects. DESIGN: A sheep model was developed to investigate this hypothesis. In four sheep, bilateral parietal bone windows were created and adjacent osteotomies performed. On the tested side, an adjacent bone segment was transported into the defect. The contralateral side was left untreated as a control. MAIN OUTCOME MEASURES: After completion of the distraction and consolidation period, a computed tomography study was performed, and the animals were sacrificed. The newly formed bone was examined macroscopically and histologically. RESULTS: A successful closure of the defect with transport distraction was achieved in all of the animals. The control side healed spontaneously in one (younger) sheep but did not heal in the other three animals. The closure of the bony defect with transport distraction was evident macroscopically as well as on the computerized tomography. Microscopic examination showed new healthy bone formation on the treated side. CONCLUSION: We conclude that transport distraction is an effective tool in closing full-thickness calvarial defects in adult sheep. Further investigation is needed before applying this promising technique in humans.

Superficial zone chondrocytes in normal and osteoarthritic human articular cartilages synthesize novel truncated forms of inter-alpha-trypsin inhibitor heavy chains which are attached to a chondroitin sulfate proteoglycan other than bikunin.

OBJECTIVE: We have examined the occurrence of the inflammation-associated inter-alpha-trypsin inhibitor (IalphaI) components, bikunin, heavy chain (HC)1 and HC2 in normal cartilage and osteoarthritis (OA) cartilage and synovial fluids. DESIGN/METHODS: Cartilage extracts from normal donors and late-stage OA patients, and synovial fluids from OA patients were studied by Western blot with multiple antibodies to bikunin, HC1 and HC2. Cell and matrix localization was determined by immunohistochemistry and mRNA by RT-PCR. RESULTS: Bikunin.chondroitin sulfate (CS) and IalphaI were abundant in OA cartilages, but virtually undetectable in normal. In both OA and normal cartilages, HCs were largely present in a novel C-terminally truncated 50-kDa form, with most, if not all of these being attached to CS on a proteoglycan other than bikunin. Synovial fluids from OA patients contained bikunin.CS and full-length (approximately 90 kDa) HCs linked to hyaluronan (HA) as HC.HA (SHAP.HA). Immunohistochemistry showed intracellular and cell-associated staining for bikunin and HCs, consistent with their synthesis by superficial zone chondrocytes. PCR on multiple human normal and OA cartilage samples detected transcripts for HC1 and HC2 but not for bikunin. In OA cartilages, immunostaining was predominantly matrix-associated, being most intense in regions with a pannus-like fibrotic overgrowth. CONCLUSION: The truncated structure of HCs, their attachment to a proteoglycan other than bikunin, PCR data and intracellular staining are all consistent with synthesis of HC1 and HC2 by human articular chondrocytes. The presence of bikunin.CS and IalphaI in OA cartilage, but not in normal, appears to be due to diffusional uptake and retention through fibrillated (but not deeply fissured) cartilage surfaces.

[Adaptation of Mycoplasma gallisepticum to unfavorable growth conditions: changes in morphological and physiological characteristics].

Adaptation of Mycoplasma gallisepticum to unfavorable growth conditions results in altered morphological and physiological characteristics of the cells. M. gallisepticum populations in a complete nutrient medium contain pear-shaped vegetative cells (d approximately 0.3 microm; l approximately 0.8 microm) with pronounced polar and cytoskeleton-like structures. Such mycoplasma cells are able to induce damage in a bacterial genome, causing an SOS response of the test strain (Escherichia coli PQ37). In a starvation medium, M. gallisepticum produces nanoforms, small coccoid cells (d approximately 0.15-0.2 microm) without either polar or cytoskeleton-like structures. Unlike vegetative cells, nanoforms do not induce genome damage. Alleviation of unfavorable growth conditions results in a reversion of nanoforms to typical vegetative cells.

[A comparative study of the inducing effect of homoserine lactone and hexylresorcinol on phenotypic dissociation in bacteria].

It has been shown that the phenotypic dissociation of Bacillus subtilis SK1 and S. typhimurium TA100 is induced by hexylresorcinol, an exogenous non-species-specific autoregulator of pleiotropic action, which is genotoxic for both pro- and eukaryotes. Nongenotoxic homoserine lactone, a chemical analogue of cell-density-responsive species-specific regulators, does not induce bacterial dissociation. The phage resistance of the S- and R-type variants of S. typhimurium TA100 induced by hexylresorcinol has been found to be the same as that of the S- and R-type salmonella variants obtained by the routine subculturing method.

[Ankle chondrocytes are more resistant to Interleukin-1 than chondrocytes derived from the knee]. / Sprunggelenkchondrozyten besitzen eine höhere Interleukin-1-Resistenz als Kniegelenkchondrozyten.

BACKGROUND: The incidence of degenerative changes and osteoarthritis is lower in the ankle than in the knee joints. This cannot be explained exclusively with differences in anatomy and biomechanical properties of these two synovial joints. Previous studies have indicated distinct differences in the biochemical composition of the extracellular matrix of articular cartilage from knee and ankle joints. The aim of this study was to identify potential metabolic differences between knee and ankle joint chondrocytes using isolated cells to distinguish the secondary effects of the resident extracellular matrix from the primary matrix-independent effects of cellular differentiation. METHOD: Isolated knee and ankle chondrocytes from the same human donor were cultured in alginate beads and subsequently exposed to a three-day pulse of the catabolic cytokine interleukin-1 (IL-1) as a model of an inflammatory episode. The metabolism of proteoglycans (PG's) was analyzed as expressed changes in 35S-sulfate incorporation into glycosaminoglycans (GAG's). RESULTS: The presence of IL-1 induced an inhibition of PG synthesis in knee and ankle articular chondrocytes. The 50% inhibitory concentration (IC50) of IL-1 was about 5 times lower for knee than for ankle chondrocytes. CONCLUSION: Ankle chondrocytes are more resistant to IL-1 induced inhibition of PG synthesis than chondrocytes from the knee.

[Clinical and genetic study in 22 patients with basal cell nevus syndrome]. / Etude clinique et recherche de mutations germinales du gène PTCH 1 dans le syndrome des hamartomes basocellulaires.

BACKGROUND: Nevoid basal cell carcinoma syndrome is an autosomal dominant disorder characterized by developmental abnormalities and cancer predisposition. The PTCH 1 gene, the human homolog of the Drosophila segment polarity gene patched, has been shown to be involved in the development of nevoid basal cell carcinoma syndrome. PTCH 1 is mapped to chromosome 9q22.3. The aim of the present study was to report on clinical and genetic characteristics in patients followed for nevoid basal cell carcinoma syndrome and to compare them to the data in the literature. PATIENTS AND METHODS: Screening for PTCH 1 mutations was done in 22 patients followed between 1981 and 2003 for clinical suspicion of nevoid basal cell carcinoma syndrome. Clinical and radiological data were reviewed retrospectively from records. Genetic analysis was performed using blood samples after patient informed consent was obtained. When possible, DNA was also analyzed from the parents of patients in whom PTCH 1 mutations were found. RESULTS: All patients had developed basal cell carcinomas: 45% palmar and plantar pitting, 62% jaw cysts and 66% calcification of falx cerebri. Medulloblastomas and meningiomas were the most common associated tumors. PTCH 1 mutations were identified in 13 patients: 6 familial cases, 3 sporadic cases and for 4 patients, it was not possible to conclude. Nine different new germ-line mutations were identified. DISCUSSION: Genetic analysis allows molecular confirmation of diagnosis in about half of all patients. Early diagnosis is essential for detection of clinical and radiological manifestations in young patients and for provision of advice concerning protection of the skin from the sunlight.

Microcystic adnexal carcinoma: report of seven cases including one with lung metastasis.

BACKGROUND: Microcystic adnexal carcinoma (MAC) is a rare cutaneous neoplasm, with a high rate of local recurrences. OBJECTIVE: A series of MAC was analyzed and compared to previously published cases. METHODS: Seven cases of MAC were identified in the register of the institution. Medical and pathological records were reviewed. RESULTS: The primary MAC were located on the face in all patients, and 85% were initially misdiagnosed. The mean follow-up duration was 108 months. The recurrence rate was high: 4 patients developed recurrences. In 3 patients, the course of the disease was severe: one of them developed pathologically proven lung metastasis. CONCLUSION: The present study and review of the literature confirm the clinically aggressive evolution of MAC and its rare ability to give rise to metastasis. Long-term clinical follow-ups with imaging investigations are mandatory.

[Hexylresorcinol induces chromosome aberrations in mouse peripheral blood cells].

Hexylresorcinol has been demonstrated to induce chromosome aberrations in eukaryotic cells at doses of 0.5, 0.05, and 0.005 mg/g body weight. The metabolic transformation of hexylresorcinol in mice decreases its genotoxic effect. The mutagenic effect is retained for three days only after the administration of the highest dose of hexylresorcinol (0.5 mg/g); during the first two days, lower doses are also genotoxic. Therefore, hexylresorcinol doses lower than 0.5 mg/g body weight are metabolized within two days to the extent precluding the expression of the cytotoxic effect. After a single administration to mice, exogenous hexylresorcinol is transformed at a rate of 0.0025-0.025 mg/day.

[Induction of SOS-response of cells exposed to autoregulatory factors of microorganisms]. / Induktsiia SOS-otveta kletki pod deistviem autoreguliatornykh faktorov mikroorganizmov.

Among examined microbial growth regulators of alkyl hydroxybenzene group (hexylresorcinol, methylresorcinol, and hydroxyethylphenol), only hexylresorcinol induces cellular SOS response, demonstrating a dose-dependent increase of the induction factor in the SOS chromotest with the Escherichia coli PQ37 strain. At the highest of used concentrations (100 micrograms/ml), hydroxyethylphenol and nonalkylated resorcinol were shown to exert a weak toxic effect, reducing the activity of constitutive alkaline phosphatase, but did not induce SOS response. Nontoxic methylresorcinol did not induce genome damage, which can trigger SOS functions. It is concluded that substitutions in phenolic ring affect genotoxic activity of alkylresorcinols.

[Significance of sentinel lymph node biopsy in Merkel cell carcinoma. Analysis of 11 cases]. / Intérêt du ganglion sentinelle dans le carcinome de Merkel. Analyse de 11 cas.

BACKGROUND: Merkel cell carcinoma is an aggressive cutaneous neoplasm with a high propensity for nodal metastases. Regional lymph node involvement develops in 45 to 65 p. 100 of patients. We evaluated in Merkel cell carcinoma the use of sentinel lymph node biopsy which allows the identification of occult nodal metastases. PATIENTS AND METHODS: Eleven patients diagnosed with Merkel cell carcinoma without clinical nodal involvement underwent pre-operative lymphoscintigraphy followed by sentinel lymphadenectomy with histologic analysis. Identification of microscopic nodal metastases led to complete lymph node dissection and adjuvant radiation therapy to the lymph node basin. RESULTS: The sentinel lymph node was successfully identified in 9 patients. Two patients demonstrated metastatic disease in their sentinel lymph nodes. At subsequent complete node dissection, one of two patients had an additional metastatic lymph node. None of the eleven patients experienced recurrent disease at a follow-up varying from 1 to 42 months. One patient with a negative sentinel lymph node experienced lymphoedema. COMMENTS: Our results are consistent with the 14 published studies which totalled 93 patients with Merkel cell carcinoma and identified 29 patients (30 p. 100) with nodal involvement. Metastatic disease was identified only after immunohistochemical analysis in 20 p. 100 of these patients (n=6). Lymph node involvement appears to be a bad prognostic factor with 29.6 p. 100 of disease recurrence, as opposed to 3 p. 100 in patients with an uninvolved sentinel lymph node. Although the prognostic significance of this technique seems interesting, there is no optimal therapeutic approach to sentinel lymph node involvement.

[Delayed cerebral radionecrosis following radiation therapy of cutaneous squamous cell carcinomas of the head]. / Radionécroses cérébrales tardives après traitement par radiothérapie de carcinomes épidermoïdes cutanés de la tête.

INTRODUCTION: Three cases of cerebral radionecrosis occurring after radiation therapy for squamous cell carcinomas of the scalp are reported. This rare and poorly documented complication of radiotherapy is discussed. CASE REPORTS: Three patients presenting with squamous cell carcinomas of the scalp were treated with surgery and radiotherapy for recurrent or incomplete resection of squamous cell carcinomas of the head. X-ray doses range were 50 to 60 Grays in 22 to 24 fractions. Cerebral radionecrotic lesions were diagnosed 6 months to 14 years after irradiation, and were inconstantly associated with clinical symptoms. The patients were treated with systemic steroids, which were of limited efficacy in one of our patients. DISCUSSION: Little is known of cerebral radionecrosis following radiotherapy. This may be related to their rare occurrence and/or to the difficulties in establishing diagnosis. The delay of occurrence after radiotherapy can vary between a few months and several years, and the lesions are directly correlated with the doses and the fractionning of the X-rays. Intracerebral localization of the tumour is the main differential diagnosis. Localized and cystic forms of cerebral radionecrosis can be treated by surgery. Treatment otherwise relies on systemic steroids.

Diffraction-enhanced X-ray imaging of articular cartilage.

OBJECTIVE: To introduce a novel X-ray technology, diffraction-enhanced X-ray imaging (DEI), in its early stages of development, for the imaging of articular cartilage. DESIGN: Disarticulated and/or intact human knee and talocrural joints displaying both undegenerated and degenerated articular cartilage were imaged with DEI. A series of three silicon crystals were used to produce a highly collimated monochromatic X-ray beam to achieve scatter-rejection at the microradian level. The third crystal (analyser) was set at different angles resulting in images displaying different characteristics. Once the diffraction enhanced (DE) images were obtained, they were compared to gross and histological examination. RESULTS: Articular cartilage in both disarticulated and intact joints could be visualized through DEI. For each specimen, DE images were reflective of their gross and histological appearance. For each different angle of the analyser crystal, there was a slight difference in appearance in the specimen image, with certain characteristics changing in their contrast intensity as the analyser angle changed. CONCLUSIONS: DEI is capable of imaging articular cartilage in disarticulated, as well as in intact joints. Gross cartilage defects, even at early stages of development, can be visualized due to a combination of high spatial resolution and detection of X-ray refraction, extinction and absorption patterns. Furthermore, DE images displaying contrast heterogeneities indicative of cartilage degeneration correspond to the degeneration detected by gross and histological examination.

Indium-111 octreotide scintigraphy of Merkel cell carcinomas and their metastases.

BACKGROUND: Somatostatin receptor scintigraphy (SRS) may be of interest for staging Merkel Cell Carcinoma (MCC). This study was undertaken to evaluate the sensitivity and specificity of SRS and to determine its role compared to conventional investigations. PATIENTS AND METHODS: From 1993 to December 2000, 20 patients (10 females and 10 males, aged from 38 to 88, mean 66 years) were included prospectively. At the time of SRS: 12 patients had been diagnosed as having stage I disease, 6 stage II and 4 stage III. Two patients had two SRS studies during the course of their disease. SRS was performed with Indium-111 pentetreotide (Octreoscan), a radiolabelled somatostatin analogue. Patients were treated according to the clinical stage. A regular follow-up was scheduled every three months. RESULTS: SRS depicted stage I and II MCC tumour sites with an overall sensitivity of 78% (95% confidence interval (CI): 40%-97%) and a specificity of 96% (81%-100%). The histopathological diagnosis was used as the gold standard. Sites visualised by SRS were compared to those detected with conventional modalities and to follow-up data for all stages: SRS visualised four out of five primary tumour sites, six out of eight lymph node sites, no skin metastases (14 sites in 2 patients), two out of three thoracic metastases and zero out of two hepatic metastases. SRS did not influence treatment decision-making in any of the cases. CONCLUSIONS: Although SRS seems highly specific in MCC and could be of help in difficult cases, it cannot be recommended for routine evaluation.

Gastrointestinal radiology in the United States: An overview of the past 50 years.

Gastrointestinal radiology has expanded its scope beyond conventional abdominal radiography, barium studies, and cholecystography. Ultrasonography allows imaging of solid abdominal organs and the intestine without the use of radiation. Computed tomography now allows comprehensive assessment of abdominal and pelvic inflammatory and infectious processes, obstruction, tumor detection and staging, and display of vasculature and blunt trauma effects that were not possible 50 years ago. Magnetic resonance imaging provides multiplanar imaging to the same degree, without the use of radiation. Barium studies of the gastrointestinal tract, enteroclysis for small-bowel assessment, and conventional radiography still have a role, despite the extensive use of fiberoptic endoscopy. Fluoroscopy is still important, but great advances in technologies have changed gastrointestinal radiology irrevocably.