[18F]Sodium fluoride PET-MRI detects increased metabolic bone response to whole-joint loading stress in osteoarthritic knees.

OBJECTIVE: Altered joint function is a hallmark of osteoarthritis (OA). Imaging techniques for joint function are limited, but [18F]sodium fluoride (NaF) PET-MRI may assess the acute joint response to loading stresses. [18F]NaF PET-MRI was used to study the acute joint response to exercise in OA knees, and compare relationships between regions of increased uptake after loading and structural OA progression two years later. METHODS: In this prospective study, 10 participants with knee OA (59 ± 8 years; 8 female) were scanned twice consecutively using a PET-MR system and performed a one-legged squat exercise between scans. Changes in tracer uptake measures in 9 bone regions were compared between knees that did and did not exercise with a mixed-effects model. Areas of focally large changes in uptake between scans (ROIfocal, ΔSUVmax > 3) were identified and the presence of structural MRI features was noted. Five participants returned two years later to assess structural change on MRI. RESULTS: There was a significant increase in [18F]NaF uptake in OA exercised knees (SUV P < 0.001, KiP = 0.002, K1P < 0.001) that differed by bone region. CONCLUSION: There were regional differences in the acute bone metabolic response to exercise and areas of focally large changes in the metabolic bone response that might be representative of whole-joint dysfunction.

[18F]NaF PET-MRI provides direct in-vivo evidence of the association between bone metabolic activity and adjacent synovitis in knee osteoarthritis: a cross-sectional study.

OBJECTIVE: Synovitis is hypothesized to play a role in the development and growth of osteophytes. Our objectives were to use hybrid positron emission tomography-magnetic resonance imaging (PET-MRI) to (1) determine whether synovitis adjacent to peripheral bone subregions with increased metabolic activity is greater than adjacent to regions without increased metabolic activity and (2) assess the association between subregional bone metabolic activity and adjacent synovitis. DESIGN: We recruited 11 participants (22 knees) with a diagnosis of OA in at least one knee. Simultaneous bilateral knee PET-MRI was performed. We quantified bone metabolic activity using the radiotracer [18F]sodium fluoride ([18F]NaF) with calculation of maximum standardized uptake values (SUVmax). Synovitis was quantified using dynamic contrast-enhanced MRI with calculation of Ktrans. Bone subregions were coded as osteophyte (OP), focal increased [18F]NaF uptake without osteophyte (FIU), or normal (no osteophyte or FIU). We used robust linear mixed effects models to assess differences in adjacent Ktrans between different subregion types and to assess association between Ktrans and adjacent SUVmax. RESULTS: 94 OPs were detected (59 MOAKS grade 1, 30 grade 2, 5 grade 3), along with 28 FIU and 18 normal subregions. Ktrans was higher adjacent to FIU (adjusted mean [95% CI] = 0.06 [0.03,0.09]) and OPs (0.08 [0.05,0.11]) when compared to normal bone subregions (0.03 [0.00,0.09]). PET SUVmax was positively associated with adjacent Ktrans (ß[95% CI] = 0.018 [0.008,0.027]). CONCLUSIONS: Synovitis is more intense adjacent to peripheral bone regions with increased metabolic activity than those without, although there is some overlap. Subregional bone metabolic activity is positively associated with intensity of adjacent synovitis.

Assessment of quantitative [18F]Sodium fluoride PET measures of knee subchondral bone perfusion and mineralization in osteoarthritic and healthy subjects.

OBJECTIVE: Molecular information derived from dynamic [18F]sodium fluoride ([18F]NaF) PET imaging holds promise as a quantitative marker of bone metabolism. The objective of this work was to evaluate physiological mechanisms of [18F]NaF uptake in subchondral bone of individuals with and without knee osteoarthritis (OA). METHODS: Eleven healthy volunteers and twenty OA subjects were included. Both knees of all subjects were scanned simultaneously using a 3T hybrid PET/MRI system. MRI MOAKS assessment was performed to score the presence and size of osteophytes, bone marrow lesions, and cartilage lesions. Subchondral bone kinetic parameters of bone perfusion (K1), tracer extraction fraction, and total tracer uptake into bone (Ki) were evaluated using the Hawkins 3-compartment model. Measures were compared between structurally normal-appearing bone regions and those with structural findings. RESULTS: Mean and maximum SUV and kinetic parameters Ki, K1, and extraction fraction were significantly different between Healthy subjects and subjects with OA. Between-group differences in metabolic parameters were observed both in regions where the OA group had degenerative changes as well as in regions that appeared structurally normal. CONCLUSIONS: Results suggest that bone metabolism is altered in OA subjects, including bone regions with and without structural findings, compared to healthy subjects. Kinetic parameters of [18F]NaF uptake in subchondral bone show potential to quantitatively evaluate the role of bone physiology in OA initiation and progression. Objective measures of bone metabolism from [18F]NaF PET imaging can complement assessments of structural abnormalities observed on MRI.

Quantitative imaging of bone-cartilage interactions in ACL-injured patients with PET-MRI.

OBJECTIVE: To investigate changes in bone metabolism by positron emission tomography (PET), as well as spatial relationships between bone metabolism and magnetic resonance imaging (MRI) quantitative markers of early cartilage degradation, in anterior cruciate ligament (ACL)-reconstructed knees. DESIGN: Both knees of 15 participants with unilateral reconstructed ACL tears and unaffected contralateral knees were scanned using a simultaneous 3.0T PET-MRI system following injection of 18F-sodium fluoride (18F-NaF). The maximum pixel standardized uptake value (SUVmax) in the subchondral bone and the average T2 relaxation time in cartilage were measured in each knee in eight knee compartments. We tested differences in SUVmax and cartilage T2 relaxation times between the ACL-injured knee and the contralateral control knee as well as spatial relationships between these bone and cartilage changes. RESULTS: Significantly increased subchondral bone 18F-NaF SUVmax and cartilage T2 times were observed in the ACL-reconstructed knees (median [inter-quartile-range (IQR)]: 5.0 [5.8], 36.8 [3.6] ms) compared to the contralateral knees (median [IQR]: 1.9 [1.4], 34.4 [3.8] ms). A spatial relationship between the two markers was also seen. Using the contralateral knee as a control, we observed a significant correlation of r = 0.59 between the difference in subchondral bone SUVmax (between injured and contralateral knees) and the adjacent cartilage T2 (between the two knees) [P < 0.001], with a slope of 0.49 ms/a.u. This correlation and slope were higher in deep layers (r = 0.73, slope = 0.60 ms/a.u.) of cartilage compared to superficial layers (r = 0.40, slope = 0.43 ms/a.u.). CONCLUSIONS: 18F-NaF PET-MR imaging enables detection of increased subchondral bone metabolism in ACL-reconstructed knees and may serve as an important marker of early osteoarthritis (OA) progression. Spatial relationships observed between early OA changes across bone and cartilage support the need to study whole-joint disease mechanisms in OA.

[The results of studies of the effect of asbestos on the health of working people and the population, conducted by the Yekaterinburg Medical Research Center].

The paper presents the basic results of 75-year studies of the Yekaterinburg Medical Research Center to evaluate the effect of asbestos on the health status of working people and the population, which have yielded basic hygienic, sanitary, clinical, epidemiological, and experimental data on the effect of asbestos on the health status of working people and the population and led to the conclusion that the center's experience in studying the problems may serve as the real basis for substantiating the safe permissible controlled use of chrysotile asbestos.

Solubility of chrysotile asbestos and basalt fibers in relation to their fibrogenic and carcinogenic action.

Fiber length and persistence are thought to be determinants for the development of toxic, fibrogenic, and carcinogenic effects of fibrous dusts. When the solubilities of chrysotile asbestos (CA) and basalt fibers (BF) were compared by measuring the loss of silica and magnesium in Leineweber's solution, CA was shown to be the more soluble. In a 6-month inhalation experiment, chrysotile at a mean concentration of 25 mg/m3 had a higher clearance rate than other comparable dusts. In acute toxicity studies, chrysotile and basalt fibers were administered intraperitoneally. At a dose of 1.7 g/kg body weight of CA, one third of the animals died. A dose of 2.7 g/kg body weight killed all the animals. With BF, even at a dose of 10 g/kg body weight all the animals survived. When the two fibers were administered over a 6-month period, either intratracheally or by inhalation, fibrotic lesions were more common in the group that received CA. Intraperitoneal administration of CA led to three times as many deaths from peritoneal mesothelioma as administration of BF. It appears, therefore, that in spite of its higher solubility and lower persistence, CA was the more toxic, fibrogenic and carcinogenic fiber, which gives rise to the hypothesis that the surface chemistry of the fibers is the determinant for biological activity.

Cimetidine disposition in patients undergoing continuous ambulatory peritoneal dialysis.

Cimetidine disposition was determined in six patients undergoing continuous ambulatory peritoneal dialysis to ascertain the need for modification of conventional dosing regimens. Blood, dialysis fluid, and urine were collected for 48 hours after administration of a single intravenous dose of cimetidine. The following values were obtained: elimination half-life, 4.3 hours; systemic or total body clearance, 191 +/- 55 ml/min; and dialysis clearance, 4.2 +/- 3.1 ml/min. Approximately 2% of a cimetidine dose is removed by dialysis, indicating that there is no need to adjust the conventional renal failure dosing regimen in patients undergoing continuous ambulatory peritoneal dialysis.

Influence of methamphetamine on nigral and striatal tyrosine hydroxylase activity and on striatal dopamine levels.

In previous reports, methamphetamine was shown to depress tyrosine hydroxylase (TH) activity in the rat corpus striatum. To evaluate further the mechanism of this decrease in TH activity, enzyme activity was measured in the rat corpus striatum and substantia nigra after repetitive and single-dose methamphetamine administration. Following repeated doses of methamphetamine, nigral TH activity decreased and reached 45% of controls at 12 hr and returned to normal at 60 hr. Striatal TH activity decreased to 40% of control at 36 hr and returned toward normal at 60 hr. When methamphetamine was administered every 6 hr for 30 hr and then discontinued, nigral TH activity returned toward control levels 4 days prior to recovery of striatal TH activity. Methamphetamine initially increased striatal dopamine levels at 6 hr (170% of control). Dopamine levels then decreased in parallel with striatal TH activity but failed to increase as the enzyme recovered. Concurrent administration of chlorpromazine with methamphetamine prevented the methamphetamine-induced decrease in nigral and striatal TH activity and striatal dopamine levels. The results indicate that the methamphetamine-induced depression of striatal and nigral TH activity may be related to increased stimulation of dopamine receptors in the striatum.

Influence of dopamine synthesis on methamphetamine-induced changes in striatal and adrenal tyrosine hydroxylase activity.

Methamphetamine in large doses decreases striatal tyrosine hydroxylase activity. This effect is prevented by neuroleptic agents such as chlorpromazine and haloperidol which would suggest that released dopamine may be involved in the response. To test this hypothesis, we have altered dopamine synthesis with alpha-methyl-p-tyrosine and L-Dopa and found that dopamine synthesis is necessary for the observed depression of striatal TH activity by methamphetamine. In the adrenal gland, however, the increase in TH activity by methamphetamine is not prevented by inhibition of catecholamine synthesis. It is possible that released dopamine may be inhibiting TH activity by activation of pre- or postsynaptic dopamine receptors in the neostriatum resulting in activation of the neuronal feedback pathway or released dopamine may act on dendrodendritic autoreceptors in the substantia nigra.

Limitations of combined flexible sigmoidoscopy and double contrast barium enema in patients with rectal bleeding.

Eighty-seven outpatients with non-massive rectal bleeding or asymptomatic positive fecal occult blood were evaluated with 35 cm flexible sigmoidoscopy, double contrast barium enema (DBCE) and colonoscopy. 82% had hemorrhoids and 35% harbored colorectal neoplasia. The combination of flexible sigmoidoscopy and DCBE missed none of 7 malignant lesions. However, 36% of benign polyps greater than or equal to 1 cm and 60.25% of those less than 1 cm were not detected by this combination. The presence of hemorrhoids should not prevent a search for colon neoplasia and colonoscopy is the preferred method.

Retrospective view of airborne dust levels in workplace of a chrysotile mine in Ural, Russia.

The Bazhenovskoye chrysotile asbestos deposit has been exploited for 115 years. All the technological operations in the quarry are accompanied by the formation of high-dispersion asbestos-containing aerosols. The dust concentrations at the miner's working places for the last 30 years (1970-2000) were at or below the Russian MACs(m.s.) level (4.0 mg/m3). The seasonal precipitation amount in the deposit area causes a rise in dust content in certain periods. The maximum density of asbestos respirable fibres exceeded 2.7 f/cm3. All the identified fibres belonged to chrysotile asbestos, and no amphibole asbestos, such as tremolite asbestos, has been identified. An excessive dust level remains, despite the dust content level decrease, at the work sites of oversized lump drillers and unloaders, and oncopathology heightened risk remains in these occupational groups, as a result.

Risk factors for asbestosis in workers of asbestos mills.

The analysis was based on a set of fifteen factors, characterising: the value of exposure to dust hazard, social status of the subjects involved, presence of diseases in the anamnesis, habits, etc., with the aim of establishing their effect on the possibility of developing asbestosis among the female workers of asbestos mills. Mathematical methods of pattern recognition were used for this multifactorial analysis. The decisive rule, obtained on the "training" principle, helped to differentiate the observations made in a reference group with the following accuracy: "without asbestosis": 87.5% correct answers, and "with asbestosis": 88.9% correct answers, which confirms the possibility of predicting the individual risk of developing asbestosis by analysing the set of risk factors. The use of the improved dermatoglyphic technique contributed to demonstrating the significance of the genotype in producing a predisposition towards asbestosis. The experience acquired demonstrates the possibility of medico-occupational selection for work involving asbestos exposure with simultaneous improvement of dust abatement measures at the factory.

[Carcinogenic hazard in the manufacture of technical-grade carbon]. / O kantserogennoi opasnosti v proizvodstve tekhnicheskogo ugleroda.

As a result of retrospective studies on cancer mortality among workers engaged in the carbon black industry, it was found that the mortality rate from cancer of the lung, stomach and gastrointestinal tract within this cohort of workers is higher compared with the population of the surrounding district and distant to it.

[The danger of developing lung cancer in the manufacture of asbestos panel]. / Opasnost' razvitiia raka legkikh v proizvodstve asbestovogo kartona.

The article presents results of study covering mortality with lung cancer among the staffers of 2 enterprises producing asbestos cardboard. The study proved that long work in dusty conditions (dust concentration nearly 1.0 mg/m3) does not result to higher risk of death with lung cancer. However the influence of increased concentrations of dust requires further investigations.

[Comparative evaluation of dust oncogenicity in asbestos-containing and non-asbestos details]. / Sravnitelnaia otsenka onkogennosti pylei asbestoformovannykh detalei na bezasbestovoi i asbestovoi osnove.

Experiments proved higher carcinogenicity of chrisotyle-asbestos than of dust appearing in mechanical processing of asbestos-containing details and in wearing articulated shoe brakes. Substitution of asbestos for basalt fibers leaves oncologic risk intact among workers engaged into mechanical processing of asbestos-containing brakes. Avoiding asbestos in mixtures for brakes could lower risk. Results support conclusions obtained by cohort studies in Yaroslavl.

[Occupational health issues at enterprises and utilization of road-building materials derived from the wastes of lead-containing enriched ore from the Aktovrak mines]. / Gigienicheskaia kharakteristika proizvodstva i primeneniia materialov dlia dorozhnogo stroitel'stva iz otkhodov obogashcheniia asbestovykh rud Aktovrakskogo mestorozhdeniia.

The article presents results of hygienic research assessing use of asbestos materials in road building. Asbestos materials used are waste products of asbestos ore enrichment at Aktovraksky layer (Tuva Republic). The main hazard was proved to be a highly dispersed asbestos-containing aerosol of complex composition, with low content of fiber particles (0.8-1.4%) and respirable fibers (0.25-6%) particularly. The calculated concentrations of asbestos fibers did not exceed the MAC adopted in most countries (1 fiber/ml). Airborne levels of asbestos in road building and exploitation are within the national standard.

[Effect of low concentration of asbestos-containing dust]. / K voprosu o deistvii nizkikh kontsentratsii asbestosoderzhashchikh pylei.

Dust, particularly fibrous, in atmosphere of Asbest town was characterized. Pulmonary cancer mortality in Asbest town and towns of nearby area were compared and no significant difference was found. Overall pulmonary cancer mortality was higher in the region than in Asbest. Obtained data served as a basis for discussion on the action threshold of asbestos-containing dust. MAC for asbestos fibers in atmosphere is reported to be 0.06 respirable fibers per ml.

[Comparative evaluation of fibrogenesis and toxicity of asbestos-containing heat-proof materials]. / Sravnitelnaia otsenka fibrogennosti i tiksichnosti asbestsoderzhashchikh teploizoliatsionnykh materialov.

The article deals with the results of studies analyzing the fibrogenic activity and toxicity of asbestos-containing heat insulators exemplified by asbestos board, vulcanite and asbestos vermiculite. Physical and chemical parameters of the studied dust are presented. All studied dust types have the distinct fibrogenic activity, the highest one was seen in asbestos board. The studied dust types could be classified according to the acute toxicity: asbestos board (DL50-3.2 +/- 0.09 g/kg), chrysotile asbestos (DL50-2.0 +/- 0.08 g/kg), vulcanite (DL50-1.9 +/- 0.08 g/kg) and asbestos vermiculite (DL50-0.7 +/- 0.04 g/kg). The article touches upon the probable acting mechanism of acute toxicity of asbestos and asbestos-containing dust.

[Occupational problems of serpentine asbestos in industry (history and trends)]. / Gigienicheskie problemy khrizotil-asbesta v promyshlennosti (istoriia i perspektivy).

The article presents summarized data of long-standing research of work conditions, asbestosis occurrence, and epidemiology of malignancies in "URALASBEST" enterprises extracting and utilizing asbestos. The research served as a base to elaborate and put into practice a complex of sanitary, technical, medical and biologic measures in various asbestos enterprises. Those measures lowered occupational morbidity due to asbestos. Considering the experience accumulated, the authors set prospects for further studies on "Asbestos and Health" problem.