Wear of retrieved UHMWPE hip liners

After the gamma-irradiation sterilization, the most widely used orthopaedic grade polymer bearing liner material for the total joint replacement, ultra-high molecular weight polyethylene (UHMWPE), degrades through the progressive in vivo oxidation. The oxidative degradation makes UHMWPE brittle and leads to reduction of its mechanical properties. In this study, the effect of the in vivo post-irradiation ageing time on the wear of UHMWPE was investigated. Twelve retrieved polyethylene hip liners implanted for 3-16 years and then stored in the air for 1.5-8 years were used. Two types of the pin-on-disk wear testing were conducted. The uni-directional repeat pass rotating and the linear reciprocating wear testing were done with stainless steel disks against stationary polyethylene pins under 4MPa at 1Hz with bovine serum lubrication. Wear of the retrieved polyethylene hip liners does not have significant correlation with the in vivo or total ageing time. The linear reciprocal sliding motion generated a more pronounced wear than the uni-directional repeat pass sliding motion. This indicates that the kinematic motion significantly affects the wear of aged UHMWPE, having a brittle, white band region.     

Hypersensitivity to Forcipomyia taiwana (biting midge): clinical analysis and identification of major For t 1, For t 2 and For t 3 allergens

BACKGROUND: Forcipomyia taiwana is a tiny, blood-sucking midge that cause intense pruritis and swelling in sensitive individuals. It is distributed island-wide in rural Taiwan and Southern China. Objective: This study aimed to study the allergic immune responses and identify F. taiwana allergens. METHODS: Crude whole body F. taiwana extracts were prepared with phosphate-buffered saline. The specific IgE antibody was determined by enzyme-linked immunoassay and immunoblotting. Protein was analyzed by electrospray ionization tandem mass spectrometry. RESULTS: Among the 372 subjects that were exposed to F. taiwana bites, 179 (48%) reported an immediate skin reaction with/without delay reaction and 41(11.1%) reported a solely delay reaction. The skin of 21 subjects was tested with F. taiwana extract. Of these 21 subjects, 12 (57.1%) produced immediate skin reactions and contained high levels of specific IgE antibody against F. taiwana. Immunoblotting revealed that 11 allergenic components are able to bind specific IgE. Allergens of 22, 24, 35, 36, and 64 kDa bound 50, 50, 75, 66.7, and 75% of IgE-containing sera tested, respectively. Tryptic fragments of the 24, 35, 36, and 64 kDa allergens were analyzed by ESI-MS/MS. Selected tryptic peptides of 24, 35, and 36, and 64 kDa allergens exhibited significant sequence identity with triosephosphate isomerase of Anopheles merus,Tenebrio molitor,Ochlerotatus togoi, and Chrysops vittatus, fructose 1,6-bisphosphate aldolase of Antheraea yamamai and Homalodisca coagulata, and a slow muscle myosin S1 heavy chain of Homarusamericanus and a protein with unknown function from A. gambiae, respectively. The 35 and 36 kDa proteins may represent different isoforms of the fructose 1,6-bisphosphate aldolase. CONCLUSION: We conclude that immediate reaction to F. taiwana bites is IgE mediated and the 24 (For t 1), 35 (For t 2), and 64 kDa (For t 3) proteins are candidates for major F. taiwana allergens. Further studies are needed to confirm these allergens.     

Nocardia osteomyelitis in a pachymeningitis patient: an example of a difficult case to treat with antimicrobial agents

Antimicrobial agents played a miraculous role in the treatment of bacterial infections until resistant bacteria became widespread. Besides antimicrobial-resistant bacteria, many factors can influence the cure of infection. Nocardia infection may be a good example which is difficult to cure with antimicrobial agents alone. A 66-year-old man developed soft tissue infection of the right buttock and thigh. He was given prednisolone and azathioprine for pachymeningitis 3 months prior to admission. Despite surgical and antimicrobial treatment (sulfamethoxazole-trimethoprim), the infection spread to the femur and osteomyelitis developed. The case showed that treatment of bacterial infection is not always as successful as was once thought because recent isolates of bacteria are more often resistant to various antimicrobial agents, intracellular parasites are difficult to eliminate even with the active drug in vitro, and infections in some sites such as bone are refractory to treatment especially when the patient is in a compromised state. In conclusion, for the treatment of infections, clinicians need to rely on laboratory tests more than before and have to consider the influence of various host factors.     

Altered expression of cell adhesion molecules in uninvolved gut in inflammatory bowel disease.

Adhesion of circulating cells to vascular endothelium occurs in the early phase of inflammation, and is mediated by specific cell adhesion molecules. Many such adhesion molecules are increased in inflamed regions of ulcerative colitis (UC) and Crohn's disease (CD) but there is limited knowledge of their expression in the uninvolved gut, adjacent to inflammation. We investigated immunohistochemically the expression of platelet endothelial cell adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) on resected specimens taken at a distance of 2-4 cm from the inflamed area and without histological signs of inflammation. Compared with normal gut, we found (i) a significant increase of PECAM-1-positive vessels in the mucosa of uninvolved UC (149.0 +/- 24.1 vessels/mm2 (mean +/- s.d.); normal colon = 123.1 +/- 21.6; P = 0.004); (ii) a significant decrease of ICAM-1-positive vessels in uninvolved CD (111.9 +/- 22.6 vessels/mm2; normal ileum = 136.9 +/- 27.6; P = 0.04); and (iii) a moderate but statistically insignificant increase of LFA-1-positive cells in the mucosa of uninvolved UC and Crohn's ileitis. This altered expression of cell adhesion molecules may contribute to the early lesion in inflammatory bowel disease and provide new therapeutic opportunities.     

Dental abnormalities in individuals with pathogenic germline variation in DICER1

Pathogenic germline variation in the microRNA processing gene DICER1 gives rise to an autosomal dominant, tumor‐predisposition disorder. Conditional deletion of Dicer1 in murine dental epithelium shows that it controls tooth patterning, size, number, and shape. The human dental phenotype of people with germline pathogenic variation in DICER1 is unknown. DICER1‐carriers (n = 57) and family controls (n = 55) were evaluated at the NIH Clinical Center dental clinic as part of a comprehensive medical evaluation. Digital panoramic radiographs, bite‐wing radiographs, and oral photographs were collected. A single observer, blind to DICER1 status, reviewed the dental records and determined the presence or absence of 11 dental characteristics as described in the clinic notes, radiographs, or oral photographs. Subjective phenotypes were reviewed on radiographs by two examiners (blind to DICER1 status) for the presence or absence of the dental characteristics to reduce inconsistencies. By simple association, bulbous crown, periodontitis, and taurodontism were all significant (p < .05). Logistic regression with chi‐square maximum likelihood estimates showed that bulbous crown and periodontitis remained significant. Recognition of these phenotypes may aid identification of individuals and families at risk for DICER1‐associated neoplasms. These findings may also guide dental care for individuals with germline DICER1 pathogenic variation.     

Simultaneous differentiation and typing of Entamoeba histolytica and Entamoeba dispar

Sequences corresponding to some of the polymorphic loci previously reported from Entamoeba histolytica have been detected in Entamoeba dispar. Comparison of nucleotide sequences of two loci between E. dispar strain SAW760 and E. histolytica strain HM-1:IMSS revealed significant differences in both repeat and flanking regions. The tandem repeat units varied not only in sequence but also in number and arrangement between the two species at both the loci. Using the sequences obtained, primer pairs aimed at amplifying species-specific products were designed and tested on a variety of E. histolytica and E. dispar samples. Amplification results were in complete agreement with the original species classification in all cases, and the PCR products displayed discernible size and pattern variations among the isolates.     

Chemical, structural properties, and osteoconductive effectiveness of bone block derived from porcine cancellous bone

The purpose of this study is to determine the efficacy of bioactive calcium phosphate obtained from porcine cancellous bone for the treatment of bone defects and nonunion. Porcine cancellous bone blocks were heat treated at 1300 degrees C for 2 h. The chemical composition, calcium-to-phosphate ratio, and microstructure of the porcine bone blocks were examined. For in vivo implantation, bone defects were created on the anteromedial aspect of the proximal tibia in seven beagle dogs and the xenograft bone blocks were placed into these defects. Plain radiographs were taken at 2-week intervals for roentgenographic evaluation. At 12 weeks, the specimens were stained with hematoxylin and eosin (H&E). The composition and morphology of heat-treated porcine cancellous bone were found to be similar to heat-treated human cancellous bone. Radiographs showed union between the host bone/bone-block interfaces. At 12 weeks, uniform and substantial new bone formation was observed. It is concluded that heat-treated porcine cancellous bone demonstrated effective osteoconductivity. This high-temperature heat-treatment technique has several advantages, including decreased risk of disease transmission and immunoreactivity, while also offering excellent biocompatibility.     

Long-term survival after autologous bone marrow transplantation for follicular lymphoma in first remission.

The role of autologous stem cell transplantation (ASCT) in the treatment of follicular lymphoma is still being defined in the era of antibody therapy. Here we report the long-term 12-year clinical outcomes of patients treated with autologous bone marrow transplantation (ABMT) for follicular non-Hodgkin's lymphoma (NHL) in first remission. Between 1988 and 1993, advanced-stage follicular NHL patients in need of initial therapy were enrolled in 2 consecutive prospective treatment trials of either standard-dose CHOP induction (83 patients) or high-dose CHOP plus granulocyte-colony stimulating factor (G-CSF) (20 patients). Patients who achieved an adequate remission with induction therapy underwent conditioning with cyclophosphamide and total body irradiation (TBI) followed by ABMT in first remission using bone marrow (BM) purged in vitro with anti-B cell monoclonal antibodies and rabbit complement (96 patients). At 12-year follow-up, 61% of the patients are alive and 43% remain in continuing complete remission. The only predictors of decreased progression-free survival proved to be histologic BM involvement at time of harvest (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.3-3.9, P<.004) and PCR detectable disease in the BM product after purging (HR 4.18, 95% CI 1.99-8.8, P=.0002). No significant predictors of overall survival were identified. These results at 12-year follow-up suggest that a subset of follicular lymphoma patients can experience prolonged survival with ABMT in first remission.     

Glucocorticoid resistance in asthma is associated with elevated in vivo expression of the glucocorticoid receptor beta-isoform

BACKGROUND: Glucocorticoid-resistant bronchial asthma is characterized by failure of corticosteroids to suppress key asthma-relevant, cell-mediated inflammatory responses in the airways. OBJECTIVE: The mechanism of this phenomenon is not clear but may involve aberrant expression of the beta-isoform of the glucocorticoid receptor. METHODS: We have measured expression of the alpha- and beta-glucocorticoid receptor isoforms in tuberculin-driven cutaneous cell-mediated inflammatory lesions in people with asthma who are glucocorticoid sensitive and resistant after 9 days of therapy with oral prednisolone (40 mg/day) or matching placebo in a random order, crossover design. RESULTS: After placebo therapy, the mean numbers of cells expressing glucocorticoid receptor alpha immunoreactivity in the lesions evoked in glucocorticoid-sensitive and -resistant patients with asthma were statistically equivalent. The numbers of cells expressing glucocorticoid receptor beta were significantly elevated in the patients who were glucocorticoid resistant, resulting in an 8-fold higher ratio of expression of glucocorticoid receptor alpha/glucocorticoid receptor beta in the patients who were glucocorticoid sensitive. Glucocorticoid receptor alpha/glucocorticoid receptors beta were colocalized to the same cells. Oral prednisolone therapy was associated with a significant decrease in the numbers of cells expressing glucocorticoid receptor alpha but not glucocorticoid receptor beta in the subjects who were glucocorticoid sensitive. No significant change was found in the numbers of cells expressing glucocorticoid receptor alpha and glucocorticoid receptor beta in the patients who were glucocorticoid resistant. Prednisolone therapy reduced the ratio of glucocorticoid receptor alpha/glucocorticoid receptor beta expression for the patients who were glucocorticoid sensitive to a level seen in the patients who were glucocorticoid resistant before therapy. CONCLUSION: Because glucocorticoid receptor beta inhibits alpha-glucocorticoid receptor-mediated transactivation of target genes, the increased expression of glucocorticoid receptor beta in inflammatory cells might be a critical mechanism for conferring glucocorticoid resistance.