Local bone loss in patients with anti-citrullinated peptide antibody and arthralgia, evaluated with high-resolution peripheral quantitative computed tomography.

OBJECTIVE: To investigate bone changes in the metacarpophalangeal (MCP) joints of anti-citrullinated peptide antibody (ACPA)-positive patients with arthralgia, but not arthritis, compared to healthy controls. METHOD: Using a cross-sectional study design, patients were recruited from hospitals and private care rheumatologists, and controls from a test subject website. All subjects underwent medical history interview, clinical examination, and biochemical screening including ACPA. Patients with positive ACPA, arthralgia, and no rheumatic disease were included. Controls without a history or signs of rheumatological disease or positive ACPA were included. A 2.7-cm-long region around the second and third MCP joints was evaluated using high-resolution peripheral quantitative computed tomography with a voxel size of 82 µm. RESULTS: Twenty-nine ACPA-positive patients and 29 healthy controls were evaluated. Trabecular volumetric bone mineral density and bone volume fraction did not differ between the groups. In addition, the cortical bone was not affected in patients, as we found no difference in average cortical thickness and cortical bone area between the groups. In contrast, the trabeculae were significantly (p < 0.05) thinner in both second and third MCP heads compared with controls, whereas trabecular number and trabecular separation did not differ between the groups. No erosions were demonstrated and the number of non-specific breaks did not differ between the groups. CONCLUSION: Trabecular bone changes were observed in ACPA-positive patients with arthralgia compared with healthy controls. The results may reflect inflammatory up-regulated trabecular bone resorption leading to early bone loss before the onset of clinical arthritis.

A Unique Model for ONSD Part II: Inter/Intra-operator Variability.

OBJECTIVE: To evauluate our novel ultrasound model for measurement of optic nerve sheath diameter (ONSD) and determine the intra- and inter-operator variability associated with this technique. METHODS: We conducted ten measurements of ONSD per model amongst eight different models with a single experienced operator to examine intra-operator variability. Similarly, we had seven different operators measure the OSND twice in eight different models, in order to determine inter-operator variability analyzed with a three level linear statistical model. RESULTS: For intra-operator variability, the intra-cluster correlation coefficients for the experienced and novice operators were 0.643 and 0.453 respectively. This displayed improvement in intra-operator variability with experience. The inter-cluster correlation coefficient was 0 for the group of novice operators, indicating negligible difference amongst multiple operators in measuring any given model of ONSD. A strong, statistically significant, linear relationship between the actual model disc size and the ultrasound ONSD measures was identified, implying the reliability of the images produced by our novel model. CONCLUSIONS: Utilizing a novel model for ONSD ultrasonography, we have determined the intraoperator reliability of ONSD measurement to be moderate, with no appreciable difference amongst multiple operators. Improvement in measurement reliability has been demonstrated between expert and novice operators with our model, indicating the potential benefit of simulation platforms for teaching the technique of ONSD ultrasound.

Diagnostic accuracy of 3D time-of-flight MR angiography compared with digital subtraction angiography for follow-up of coiled intracranial aneurysms: influence of aneurysm size.

BACKGROUND AND PURPOSE: 3D time-of-flight MR angiography (3D TOF MRA) may be used as noninvasive alternative to digital subtraction angiography (DSA) for the follow-up of patients with intracranial aneurysms treated with Guglielmi detachable coils (GDCs). We aimed to determine the influence of aneurysm size and location on diagnostic accuracy of 3D TOF MRA for follow-up of intracranial aneurysms treated with GDCs. MATERIALS AND METHODS: Two hundred and one 3D TOF MRAs in 127 consecutive patients with 136 aneurysms were compared with DSA as standard of reference. Sensitivity and specificity of 3D TOF MRA for detection of residual or reperfusion of the aneurysms was calculated with regard to aneurysm size and location. RESULTS: Overall sensitivity and specificity of MRA was 88.5% and 92.9%, respectively. Sensitivity was lower for aneurysms

Marine debris in harbour porpoises and seals from German waters.

Records of marine debris in and attached to stranded harbour porpoises (Phocoena phocoena), harbour seals (Phoca vitulina) and grey seals (Halichoerus grypus) were studied comprising information on 6587 carcasses collected along the German coast between 1990 and 2014, the decomposition state allowed for necropsy in 1622 cases. Marine debris items were recorded in 31 carcasses including 14 entanglements (5 harbour porpoises, 6 harbour seals, 3 grey seals) and 17 cases of ingestion (4 harbour porpoises, 10 harbour seals, 3 grey seals). Objects comprised general debris (35.1%) and fishing related debris (64.9%). Injuries associated with marine debris included lesions, suppurative ulcerative dermatitis, perforation of the digestive tract, abscessation, suppurative peritonitis and septicaemia. This study is the first investigation of marine debris findings in all three marine mammal species from German waters. It demonstrates the health impacts marine debris can have, including severe suffering and death. The results provide needed information on debris burdens in the North and Baltic Seas for implementing management directives, such as the Marine Strategy Framework Directive (MSFD).

Modification of human leukocyte interferon pharmacology with a monoclonal antibody.

The antitumor and antiviral properties of the interferons have been well established. However, the usefulness of the interferons may be limited, in part, because of rapid clearance from the plasma and degradation by plasma or tissue enzymes. A monoclonal antibody (IFG-252.2) was developed which binds to recombinant DNA-produced human alpha-interferon (rIFN-alpha A) without measurably reducing its in vitro antiviral or antiproliferative properties. Pharmacokinetic studies of rIFN-alpha A:antibody complex in the intact, anesthetized rat showed that rIFN-alpha A activity cleared from plasma 3-fold slower than found after injection of free rIFN-alpha A. This resulted in a 15-fold increase in its calculated area under concentration curve compared to that of free rIFN-alpha A. These studies suggest that interferon bound to a monoclonal antibody may provide a means to prevent the normal clearance and degradation of free interferon and may result in prolonged antitumor and antiviral plasma activity in vivo. Furthermore, it suggests that monoclonal antibodies to various biologically active agents may be used to favorably alter their pharmacokinetics while leaving their biological activity unaltered.

Nucleotide sequence of the gene, protein purification and characterization of the pSC101-encoded tetracycline resistance-gene-repressor.

The nucleotide sequence of the pSC101-encoded tetracycline repressor gene (tetR) was confirmed. The deduced amino acid sequence is compared to that of other repressor proteins. To overproduce the repressor protein, tetR was placed under the control of bacteriophage lambda promoter pL. Tet repressor protein was purified to homogeneity and shown to bind specifically to two tet operators and also to tetracycline (Tc). The inducer function of Tc is demonstrated by the loss of the specific binding between the tet operator DNA and the Tet repressor-Tc complex.

[Digital 3D rotational angiography for the preoperative and preinterventional clarification of cerebral arterial aneurysms]. / Digitale 3D-Rotationsangiographie zur präoperativen und präinterventionellen Abklärung von Hirnarterienaneurysmen.

OBJECTIVE: Does the recently introduced 3D angiography provide additional information beyond standard angiography (DSA) for the diagnosis of cerebral aneurysms? METHODS: During a 3-months period DSA and 3D-angiography were performed in 40 patients harbouring a total of 49 aneurysms. Vascular regions that presented an aneurysm diagnosed by DSA were reevaluated by 3D-angiography. RESULTS: In two patients, vessel-loops previously described as aneurysms by DSA could be identified by 3D-angiography. In one patient, an aneurysm was diagnosed that could not be detected by DSA. In another case, the definitive diagnosis of an aneurysm was obtained only with 3D-angiography. In one patient, an aneurysm was diagnosed that could not be detected by DSA. In another case, the diagnosis of an aneurysm was obtained only with 3D-angiography. In two cases, aneurysms could be definitively excluded by 3D-angiography, whereas in another aneurysm a vessel originating from this lesion was identified. The size of the aneurysms measured by both methods was identical. CONCLUSIONS: Multiple projections of 3D-angiography provide a better evaluation of the anatomic situation regarding the base of the aneurysm as well as the relationship of an aneurysm to neighbouring vessels. Further, an exact differentiation between a vessel loop and an aneurysm can be made. Therefore, 3D-angiography is a valuable tool when used in conjunction with DSA.

[Differential diagnosis of space-occupying adrenal masses]. / Differentialdiagnose raumfordernder Prozesse der Nebennieren.

Computed tomography (CT) and magnetic resonance (MR) imaging are first line modalities in the evaluation of patients with adrenal gland masses, and have the potential to be very accurate for the localization of adrenal gland masses in patients with diseases associated with hyperfunctioning conditions of the adrenal gland. Both CT and MR imaging allow a specific diagnosis of acute adrenal hemorrhage, adrenal myelolipoma, and adrenal cysts. CT is also helpful in the assessment of patients with Addison's disease, particularly the subacute form secondary to granulomatous diseases. Quantitative evaluation of adrenal masses on unenhanced CT scans and/or qualitative analysis on chemical-shift MR imaging have been shown to be accurate in distinguishing adrenal adenomas from non-adenomas. Attenuation of 11 HE or less on unenhanced CT scans and/or signal loss on opposed phase MR images indicate adenoma with a high specificity and acceptable sensitivity. More recently, delayed-enhanced CT has yielded higher sensitivity and specificity values in distinguishing between adrenal adenomas and non-adenomas than both unenhanced CT and chemical-shift MR imaging do. On delayed-enhanced CT scans, adrenal adenomas exhibit a greater washout of contrast material than do adrenal non-adenomas. Therefore, adrenal non-adenomas have significantly higher attenuation than adenomas on delayed-enhanced CT scans obtained at several arbitrarily chosen time points (3-60 min) after the initiation of contrast material administration.

Effects of restructuring on the performance of microbiology laboratories in Alberta.

OBJECTIVE: To evaluate the error rates of organism identification and antibiotic susceptibility proficiency testing challenges before, during, and after microbiology laboratory restructuring in Alberta. METHODS: Alberta Health substantially reduced and redistributed laboratory funds to the regional health authorities in 1995, forcing a dramatic restructure of services. Many rural hospitals expanded their microbiology test menus, and urban centers consolidated microbiology testing into a centralized high-volume laboratory. The Laboratory Proficiency Testing Program of the College of Physicians and Surgeons of Alberta mailed regular test profile surveys to microbiology laboratories during the restructure period to determine the type and extent of changes in services. Based on the types of tests and the extent of analysis being done, most rural B-level and some C-level laboratories were reclassified to the A level. The Laboratory Proficiency Testing Program reviewed the error rates of proficiency challenges based on the performance of different levels of laboratories before and after the period of restructure. RESULTS: Overall performance has improved according to the number of errors documented on identification and susceptibility challenges for laboratories that remained at the same classification (ie, A or C). The number of major identification errors for laboratories that were reclassified increased, but the rate of major susceptibility errors decreased. More reclassified laboratories do not have dedicated registered technologist(s) who perform microbiology testing and are not supervised by an on-site pathologist and/or medical microbiologist compared with laboratories that remained at the same classification. CONCLUSIONS: Microbiology laboratory restructuring will have adverse effects on the quality of complex testing if experienced technologists are not retained and services are not medically supervised.

Incidence of work-related low back pain in physical therapists.

The purpose of this study was to determine the incidence of work-related low back pain (LBP) in physical therapists and to identify common characteristics of therapists who reported work-related LBP. Questionnaires were mailed to a random sample of 500 registered physical therapists. Of the 344 (69%) questionnaires returned, 29 percent reported work-related LBP. The initial onset most frequently occurred between the ages of 21 and 30 years and within the first four years of experience as a physical therapist. Eighty-three percent of the therapists first incurred work-related LBP during treatment of patients, primarily in acute care and rehabilitation facilities. "Lifting with sudden maximal effort" and "bending and twisting" were frequent mechanisms of injury. Further research is necessary to investigate the effect work-related LBP has on productivity and quality of patient care within facilities and to identify preventive measures to decrease the incidence of work-related LBP.

[Nutritional status of Danish patients with rheumatoid arthritis and effects of a diet adjusted in energy intake, fish content and antioxidants]. / Ernaeringstilstanden for danske patienter med reumatoid arthritis og virkningen af en kost der korrigeres for energiindhold, fisk og antioxidanter.

This study deals with the nutritional status of Danish rheumatoid arthritis (RA) patients and addresses the question whether or not RA can be directly influenced by dietary manipulation. In a prospective, single-blinded study of six months' duration, 109 patients with active RA were randomly assigned to treatment with or without a specialized diet. The energy consumption was adjusted to normal standards for body-weight and the intake of fish and antioxidants was increased. A daily food diary was completed by the patients, and the total intake of 47 different food-elements was calculated. Nutritional status together with disease activity parameters were recorded. At baseline, the Danish RA-patients had neglected food habits with a significant reduction in intake of total energy, of D-vitamin and of E-vitamin. A very low intake of n-3 fatty acids was also found. During the study, 28 of the 109 patients dropped out, introducing a confounding effect on the overall result. In the remaining 81, those following the diet demonstrated a significant improvement in the duration of morning stiffness, the number of swollen joints, the pain status and reduced the cost of medicine, while doctors' global assessment, laboratory data, X-ray and the daily activities were unaltered. In conclusion, dietary analysis and appropriate, corrective advice should be offered to Danish RA patients.

Roughness Perception in Virtual Textures.

Haptic devices allow the production of virtual textured surfaces for psychophysical experiments. Some studies have shown inconsistencies between virtual and real textures with respect to their psychophysical functions for roughness, leading to speculation that virtual textures differ in some way from real ones. We have determined the psychophysical function for roughness using textures rendered with a high-fidelity magnetic levitation haptic device. A constraint surface algorithm was used to simulate the motion of a spherical probe over trapezoidal gratings and randomly dithered cones. The shape of the psychophysical functions for roughness is consistent between subjects but varies with changes in texture and probe geometry. For dithered cones, inverted "U"-shaped functions were found nearly identical, in maxima and curvature, to those in the literature for real textures with similar geometry.

Correlation of thermodynamic and genetic properties in the Tn10 encoded TET gene control region.

The thermal stability of the Tn10 encoded tetracycline resistance (TET) gene control region is investigated by melting studies using purified DNA restriction fragments containing various amounts of flanking sequences. In order to study the thermodynamic properties of this control region under conditions, where enough flanking DNA is present to mimic the situation in the chromosome, the five step melting process of a 1450-bp DNA fragment is analyzed. Because most of the sequence of this DNA is not known, the assignment of the melting transitions to segments of the DNA is done by an experimental method. This employs the preparation of subfragments from the 1450-bp DNA and comparison of their denaturation profiles with the one of the intact sequence. This approach results in the complete assignment of the five denaturation steps. Rather than from the ends, the unwinding starts from the TET gene control region in the middle of the 1450-bp sequence. A clear correlation between the thermodynamic and genetic properties of this DNA is observed. The regulatory sequence forms a small cooperative unit with the lowest stability in the entire fragment. The thermal denaturation of the TET repressor. TET operator complex reveals, that the TET repressor specifically recognizes the double stranded TET operator DNA and stabilizes this structure by 2.4 degrees C. This results is also discussed as an example of the possible action of denaturing or stabilizing proteins on this genetic control region.

Caulobacter crescentus cell envelope: effect of growth conditions on murein and outer membrane protein composition.

The murein and membrane protein compositions of Caulobacter crescentus strains CB13B1a and CB15 have been characterized, and the influence on cell envelope constituents of culture conditions which affect morphogenesis have been studied. Amino acid and sugar analysis of murein sacculi revealed a simple A1gamma murein configuration typical of gram-negative bacteria. The membranes of C. crescentus had low levels of 2-keto-3-deoxyoctonate relative to enteric bacteria, in addition to the absence of lipid A components (Shapiro et al., Science 173:884-892, 1971; Chow and Schmidt, J. Gen. Microbiol, 83:369-373, 1974). Nevertheless, C. crescentus membranes could be fractionated into inner and outer membrane components by sucrose density gradient centrifugation procedures developed for Escherichia coli. The proteins of the outer membrane were distributed between three major (I, II, and III) and two minor (IV and V) protein classes. Class I proteins were greater than or equal to 74,000 daltons and constituted the primary proteins of the outer membrane. Class I proteins were separated into approximately 50 polypeptides by two dimensional gel electrophoresis; the protein composition of thi s class was affected by culture conditions in both CB13B1a and CB15. Class II (47,000 to 39,000 daltons) and III (20,000 to 11,500 daltons) proteins differed in each strain in composition and response to culture conditions.

Nuclear mutations conferring oligomycin resistance in Neurospora crassa.

Mutants of Neurospora crassa have been isolated that are highly resistant to inhibition by oligomycin, an inhibitor of mitochondrial ATPase activity. Dixon plots (Dixon, M., and Webb, E.C. (1964) Enzymes, 2nd Ed, pp. 328-330, Academic Press, New York) of oligomycin inhibition curves of the parent strain and the resistant mutants are linear, indicating that oligomycin interacts at a single site within the ATPase complex. The Ki values obtained from the mutants vary from 150 to 900 times greater than the Ki obtained for the parent strain. The parent strain and the oligomycin-resistant mutants are also inhibited by bathophenanthroline, a lipophilic chelating agent that inhibits F1 ATPase activity. Dixon plots of bathophenanthroline inhibition curves are also linear and Ki values obtained are all approximately equal. Crosses of the oligomycin-resistant mutants to the oligomycin-sensitive parent strain show a mendelian segregation of the resistance characteristic. These data show that mutations leading to oligomycin resistance in Neurospora are due to alterations in nuclear genes.