Radiological diagnosis of periapical bone tissue lesions in endodontics: a systematic review.

This systematic review evaluates the diagnostic accuracy of radiographic methods employed to indicate presence/absence and changes over time of periapical bone lesions. Also investigated were the leads radiographic images may give about the nature of the process and the condition of the pulp in nonendodontically treated teeth. Electronic literature search included the databases PubMed, Embase and CENTRAL from January 1950 to June 2011. All languages were accepted provided there was an abstract in English. The MeSH terms were 'Cone beam computed tomography (CBCT)', 'Radiography, panoramic', 'Periapical diseases', 'Dental pulp diseases', 'Sensitivity and specificity', 'receiver operating characteristics (ROC) curve', 'Cadaver', 'Endodontics' and 'Radiography dental'. Two reviewers independently assessed abstracts and full text articles. An article was read in full text if at least one of the two reviewers considered an abstract to be potentially relevant. Altogether, 181 articles were read in full text. The GRADE approach was used to assess the quality of evidence of each radiographic method based on studies of high or moderate quality. Twenty-six studies fulfilled criteria set for inclusion. None was of high quality; 11 were of moderate quality. There is insufficient evidence that the digital intraoral radiographic technique is diagnostically as accurate as the conventional film technique. The same applies to CBCT. No conclusions can be drawn regarding the accuracy of radiological examination in identifying various forms of periapical bone tissue changes or about the pulpal condition.

Diagnosis of the condition of the dental pulp: a systematic review.

The aim of this systematic review was to appraise the diagnostic accuracy of signs/symptoms and tests used to determine the condition of the pulp in teeth affected by deep caries, trauma or other types of injury. Radiographic methods were not included. The electronic literature search included the databases PubMed, EMBASE, The Cochrane Central Register of Controlled Trials and Cochrane Reviews from January 1950 to June 2011. The complete search strategy is given in an Appendix S1 (available online as Supporting Information). In addition, hand searches were made. Two reviewers independently assessed abstracts and full-text articles. An article was read in full text if at least one of the two reviewers considered an abstract to be potentially relevant. Altogether, 155 articles were read in full text. Of these, 18 studies fulfilled pre-specified inclusion criteria. The quality of included articles was assessed using the QUADAS tool. Based on studies of high or moderate quality, the quality of evidence of each diagnostic method/test was rated in four levels according to GRADE. No study reached high quality; two were of moderate quality. The overall evidence was insufficient to assess the value of toothache or abnormal reaction to heat/cold stimulation for determining the pulp condition. The same applies to methods for establishing pulp status, including electric or thermal pulp testing, or methods for measuring pulpal blood circulation. In general, there are major shortcomings in the design, conduct and reporting of studies in this domain of dental research.

Mapping and partial characterization of proteases expressed by a CHO production cell line.

The proteolytic activities expressed by a Chinese hamster ovary (CHO) cell line in the cultivation supernatant during the production of recombinant factor VIII were mapped with a broad spectrum protease assay and a series of different types of protease inhibitors. The destabilizing effect on the product emanated from a metalloproteinase, which could be effectively blocked by chelating agents to lead to product stabilization. Amino acid sequences of the isolated metalloproteinase were found to have sequence homology with matrix metalloproteinases (MMPs) MMP3, MMP10, and MMP12. Several species with metalloproteinase activity were characterized and found to be related to each other. The results indicate that an MMP pro-enzyme of >/=200 kDa was released from the CHO cells during the production phase. The enzyme expressed collagenase/gelatinase activity when activated. Due to autoproteolysis, a number of smaller, less specific MMPs were formed with the smallest form, a 19.4 kDa protein, being the most active. These results may be of particular relevance for other production processes using CHO cells for the expression of recombinant proteins.

Structural and functional characterization of B-domain deleted recombinant factor VIII.

A new high-purity recombinant factor VIII preparation has been developed for the treatment of hemophilia A. Structurally, this factor VIII preparation, B-domain deleted recombinant factor VIII (BDDrFVIII), differs from other recombinant and plasma-derived factor VIII preparations in that most of the B-domain has been deleted. To ensure that BDDrFVIII contains the requisite structural and functional features, it has been subjected to detailed biochemical and biophysical characterization in comparison to the plasma-derived form of factor VIII. Laboratory studies have shown that the primary, secondary, and tertiary structures of BDDrFVIII and the posttranslational modifications are similar to those of the [80 + 90]-kd form of plasma-derived factor VIII. In addition, BDDrFVIII has full biologic activity compared with full-length factor VIII preparations.

Structural and functional characteristics of the B-domain-deleted recombinant factor VIII protein, r-VIII SQ.

Recombinant factor VIII SQ (r-VIII SQ), ReFacto, is a recombinant factor VIII product similar to the smallest active factor VIII protein found in plasma-derived factor VIII (p-VIII) concentrates. The protein comprises two polypeptide chains of 80 and 90 kDa and lacks the major part of the heavily glycosylated B-domain i.e. amino acids Gln744 to Ser1637. r-VIII SQ retains six potential glycosylation sites for N-linked oligosaccharides at asparagine residues 41, 239, 582, 1685, 1810 and 2118. We describe a thorough comparison of the characteristics of r-VIII SQ with those of p-VIII. The primary and secondary structures of r-VIII SQ were in good agreement with that of B-domain-deleted p-VIII (p-VIII-LMW) as shown by SDS-PAGE, Western blotting with antifactor VIII antibodies, tryptic mapping, amino acid sequence analysis and circular dichroism spectroscopy. A few divergences also existed. Thus r-VIII SQ was shown to contain a small amount of the single chain primary translation product of 170 kDa and also the product specific sequence of 14 amino acids, the SQ-link, in the C-terminal end of the 90 kDa chain. It was shown that r-VIII SQ had a high specific activity of about 14,000 IU VIII:C/mg as determined by use of a chromogenic substrate assay. The r-VIII SQ protein was comparable to p-VIII forms with a retained B-domain, in terms of potency measured by a chromogenic substrate or a two-stage clotting assay, in interactions with thrombin, and with activated protein C (APC) in combination with Protein S. The ability of r-VIII SQ to participate as a cofactor in factor Xa generation in a mixture of factors IXa and X, phospholipid and calcium was in conformity with that of p-VIII. Furthermore r-VIII SQ had a good binding capacity for phospholipid vesicles and von Willebrand factor (vWF) as shown in gel filtration studies. The same kinetics in binding to von Willebrand factor was found for r-VIII SQ and p-VIII as determined by real-time biospecific interaction analysis (BIA) with use of the BIAcore instrument. The apparent association rate constant was 4 x 10(6) M(-1)s(-1). Two dissociation rate constants were found, 1 X 10(-2)s(-1) and 4 x 10(-4)s(-1). The results extend the present knowledge that the factor VIII B-domain is dispensable for the factor VIII cofactor function in hemostasis.

Computer-aided risk management--a software tool for the Hidep model.

OBJECTIVE: The Hidep risk management model has been developed and tested in clinical settings with promising results, but a tool facilitating the work has been suggested. The aim of the present study was to create and evaluate a computerized tool capable of creating overviews of the oral health situation as well as identifying risk factors and at-risk patients. The system developed should also facilitate the clinical work, for example, by assisting the user with automatic calculation of suitable Hidep groups and selection and printing of relevant patient information letters. METHOD AND MATERIALS: The system developed was based on the Hidep model, combining a number of available examination methods, risk estimation systems, and treatment suggestions. The development strategy included stepwise improvements and functionality increase based on continuous clinical applicability tests in a large international test bed. RESULTS: The results indicated that the software created was user friendly enough to be used in a common dental clinic and capable of handling the basic data of both patients and their oral health situation. The system could present useful statistics and graphs describing the overall oral health situation and identifying relevant risk groups and risk factors, based on virtually unlimited parameter combinations. CONCLUSION: The computer system developed seems to be an important step toward the possibility of creating a close-to-the-clinic model for oral health care management based on actual and locally derived patient data and risk factors. The results of this project encourage further studies of the Hidep model and its computer support.

Influence of phospholipids on the assessment of factor VIII activity.

In view of reported discrepancies between different factor VIII assays, the influence of phospholipids on the performance of one-stage clotting (OS) and chromogenic substrate (CS) assays was evaluated. The B domain deleted recombinant factor VIII, rVIII SQ, two full-length recombinant products and a plasma derived factor VIII concentrate were each diluted into severe haemophilia A plasma and assayed against a plasma standard. The one-stage activity was 50, 80, 75 and 106%, respectively, of the chromogenic result. Variations in the phospholipid concentration did not affect the chromogenic assay, except at very low levels where the apparent activity increased. In contrast, dilution of the phospholipid reagent had a substantial influence on the activity measured by OS assays, especially in the case of rVIII SQ. At low levels of phospholipid, the one-stage activity of rVIII SQ exceeded the chromogenic result. When mixtures of phosphatidylserine (PS) and phosphatidyl-choline (PC) were used as a source of phospholipid, the OS results for rVIII SQ agreed well with the CS activity as long as the content of PS was below 10%, i.e., closer to the physiological level. At higher levels of PS, as in most commercial APTT reagents, the OS activity decreased. When the APTT reagent was replaced by platelets in the OS assay, the results compared well with those obtained by the CS assay for both t-VIII SQ and full-length factor VIII products.

Novel forms of B-domain-deleted recombinant factor VIII molecules. Construction and biochemical characterization.

Recombinant molecules similar to the smallest active plasma-derived factor VIII molecule, a complex of an 80-kDa and a 90-kDa polypeptide chain lacking the B domain, have been produced using various factor VIII cDNA constructs in order to obtain primary translation products which were efficiently processed into the 80 + 90-kDa complex. Three types of single-chain cDNAs encoding B-domain-deleted derivatives factor VIII were designed, taking account of sites at Arg740 and Glu1649, assumed to be important for processing factor VIII. In the type 1 constructs, either Arg747, Arg752, or Arg776 in the N-terminal region of factor VIII B domain was fused to the N-terminus (Glu1649) of the 80-kDa subunit. In the type 2 construct r-VIII SQ, Ser743 was fused to Gln1638, creating a link of 14 amino acids between the C-terminus (Arg740) of the 90-kDa chain and N-terminus of the 80-kDa chain, whereas in type 2 r-VIII RH, Arg747 was fused to His1646. In the type 3 constructs, the B-domain was completely removed or replaced with 1-4 Arg residues. After expression in Chinese hamster ovary cells, the type 1 derivatives and the type 3 derivatives with 0-2 Arg residues inserted were found to be only partially processed and contained a large amount of the 170-kDa primary translation product. In contrast, most of the type 2 derivatives r-VIII SQ and r-VIII RH and the type 3 derivatives r-VIII R4 and r-VIII R5 containing three or four extra Arg residues preceding the N-terminus of the 80-kDa chain were processed into the desired 80 + 90-kDa chain complexes. The feature common to the most efficiently processed factor VIII deletion derivatives was that they contained the recognition motif for proteolytic cleavage by the membrane-bound subtilisin-like protease furin, which is expressed in most types of cells; that is, basic amino acid residues at positions -1 and -4 relative to the cleavage site at Glu1649. Biochemical studies of r-VIII SQ and r-VIII R5, two of the most effectively processed factor VIII derivatives, showed that both proteins had a normal factor VIII cofactor function, and had N- and C-termini of the 80-kDa and 90-kDa chains corresponding to those found in plasma-derived factor VIII.

[Partial versus total meniscectomy. A prospective, randomized study]. / Partiel versus total meniskektomi. Et prospektivt, randomiseret studie.

Two hundred patients with a meniscus lesion were peroperatively allocated to partial or total meniscectomy. The results were compared at one year and at 6.3-9.8 years (median 7.8). After one year, more patients with partial meniscectomy (90%) than with total meniscectomy (80%) had no complaints (p = 0.029). At the late review these figures were 62% and 52% respectively (p = 0.18). However, patients with partial meniscectomy had the highest functional scores. In five percent knee joint function had improved and in 35% deteriorated, in the latter group without detectable difference between partial and total meniscectomy. The incidence of lateral laxity rose from eight to 47%, most frequently seen after total meniscectomy. During the observation period radiological signs of knee joint degeneration changed from solely joint line narrowing into additional ridge formation and flattening of the femoral condyle, but unrelated to whether partial or total meniscectomy had been performed. Following partial meniscectomy posterior horn lesions had the poorest functional outcome, but only if more than one third of the meniscal surface had been removed. The amount of meniscal tissue excised was inversely correlated to the level of knee joint function except in bucket handle lesions treated with partial meniscectomy. These lesions had the largest areas of meniscal tissue removed, but higher functional scores than posterior horn lesions. Preservation of the peripheral rim of the meniscus following partial meniscectomy was essential for the functional outcome after surgery.

The long term outcome of open total and partial meniscectomy related to the quantity and site of the meniscus removed.

Two hundred patients were randomly selected for either a partial or a total meniscectomy for a meniscal tear during open operation. They were followed for a median of 7.8 years after operation. After partial meniscectomy, posterior horn tears had the worst outcome, but this was only apparent when more than two-thirds of the meniscus had been removed. The amount of meniscal tissue excised was inversely related to the function of the knee, except with bucket-handle tears treated by partial meniscectomy. Patients with bucket-handle, anterior and posterior horn tears had similar functional results after total meniscectomy. Preservation of the peripheral rim of the meniscus following partial meniscectomy produces the best functional results.

Partial versus total meniscectomy. A prospective, randomised study with long-term follow-up.

Two hundred patients with a meniscal lesion were peroperatively allocated to partial or total meniscectomy in a random manner. The results were compared at one year and at 6.3 to 9.8 years (median 7.8). After one year more patients with partial meniscectomy (90%) than with total meniscectomy (80%) had no complaints. At the later review these figures were 62% and 52%, respectively (p = 0.18). However, patients with partial meniscectomy had higher functional scores. The deterioration in function between the first review and the second showed no significant difference in the two treatment groups. The incidence of mediolateral instability rose from 8% to 47% and was more frequent after total than after partial meniscectomy. Between the two reviews the radiological signs of knee degeneration increased with no difference between the two treatment groups.

[Screening for diabetic retinopathy]. / Screening for diabetisk retinopati.

Photographic screening for diabetic retinopathy has been carried out for 40 months in an Eye Department. The results are described, with particular emphasis on cost-benefit. It is shown that the procedure finances itself with a wide margin. It probably provides better control of retinopathy than traditional clinical procedures. There may thus be a potential to reduce human suffering and the cost to society of visual impairment. The screening also provides the Department with better photographic services in general.

Characterization of human factor VIII and interaction with von Willebrand factor. An electron microscopic study.

Blood coagulation factor VIII is a large glycoprotein that circulates in plasma at relative low concentration (0.1 microgram/ml). It consists of a heterogeneous mixture of a series heavy-chain peptides (90-200 kDa), each associated with a light chain of 80 kDa. To gain insight into the physical properties of the protein, we have characterized purified human factor VIII by electron microscopy and rotary shadowing. Electron microscopy of rotary shadowed factor VIII molecules showed predominantly a single globular domain structure, with a somewhat asymmetric shape, while two-domain structures were also encountered. The overall dimensions of the globular domains ranged from 4 x 6 nm to 8 x 12 nm. EDTA treatment of factor VIII reduced the overall dimensions (2.5 x 5 nm to 6 x 10 nm) while treatment with thrombin reduced the dimensions to a small extent. In complexes with von Willebrand factor, factor VIII appeared localized at the globular domains of von Willebrand factor multimers. In addition, incubation of factor VIII with Staphylococcus aureus V8 protease fragments SpII and SpIII revealed only binding to the globular domains of SpIII. In this study, the first morphological characterization of human factor VIII is presented, together with its direct localization on von Willebrand factor multimers.

Detection and quantitation by lysis-filtration of bacteremia after different oral surgical procedures.

Patients with bacteremia after dental extraction, third-molar surgery, dental scaling, endodontic treatment, and bilateral tonsillectomy were studied by means of lysis-filtration of blood samples with subsequent aerobic and anaerobic incubation. Samples were obtained before, during, and 10 min after treatment. Bacteremia was observed in 100% of patients after dental extraction, 55% of patients after third-molar surgery, 70% of patients after dental scaling, 20% of patients after endodontic treatment, and 55% of patients after bilateral tonsillectomy. Anaerobic microorganisms were isolated more frequently than aerobic microorganisms were, and viridans group streptococci were the most commonly isolated bacteria. Ten minutes after treatment, the frequency as well as the magnitude of bacteremia showed pronounced reduction.

Secretion of coagulant factor VIII activity and antigen by in vitro cultivated rat liver sinusoidal endothelial cells.

Different types of liver cells and a few extrahepatic cell types were analysed for the presence and production of factor VIII activity (VIII:C). Only freshly prepared suspensions of rat liver sinusoidal cells and pure monolayer cultures of rat liver endothelial cells (LEC) were found to contain and secrete detectable amounts of the coagulation factor. Secretion of VIII:C by cultured LEC was inhibited by cycloheximide and by monensin. Constant levels of VIII:C were produced for at least 48 h suggesting continuous synthesis rather than a burst release of stored material. VIII:C, as measured spectro-photometrically by conversion of X to Xa, was inhibited by anti-human VIII:C antiserum. Indirect immunocytochemistry using this antiserum gave positive staining only with LEC. Immunoprecipitation of metabolically labelled proteins in conditioned rat LEC medium with the anti human VIII:C antiserum revealed the presence of proteins of similar sizes to those reported for human VIII:C. These results indicate that rat LEC are an important site for production and secretion of procoagulant factor VIII and are not only a site for storage and release of the factor. The established conditions for synthesis of VIII:C in in vitro cultivated rat LEC should provide the means to study the regulation of VIII:C synthesis.

Plasmacytoma of the uvea in a case of multiple myeloma.

A case of plasmacytoma in the uvea, both clinically and grossly anatomically mimicking a malignant melanoma, is described in a 63-year-old man who died from multiple myeloma. This is an extremely rare condition in the eye. Only one report of a similar tumour has been found in the literature.

A comparison between different models of the relation between recorded intradental nerve impulse activity and reported pain in man.

In this study three different models of the relation between intradental nerve impulse activity (INA) and pain report, expressed by finger-span (FS), in man were investigated. The techniques were (i) a previously described mathematical model, (ii) the relation between the Areas of INA and FS and (iii) the relation between the Peaks of INA and FS. Their usefulness in 533 clinical experiments on 15 subjects were evaluated by means of a statistical analysis of the variability and accuracy of the models. It was shown that the mathematical model was the most accurate and stable method of the three different methods investigated. This was indicated by, among other things, a significantly smaller variability for the mathematical model within experimental sessions than between sessions. The two other methods were found to be of less scientific value since they had an undesired high variability within sessions, and also showed contradicting results during control conditions.