Usefulness of discography, discoblock and a new mechanical method for identifying a painful segment/disc.

BACKGROUND: We previously described a procedure for eliciting deep spatial discrimination of individual segments in the healthy lumbar spine of normal subjects: the percutaneous mechanical provocation (PMP) test. Our goal was to devise a method for accurate identification of the spinal level of pathology in chronic low back pain (CLBP). In the present study, we validated the PMP test, using a subgroup of CLBP patients with isthmic spondylolisthesis (IS). Because there is clinical consensus that IS back pain originates in the slipped segment/disc, the level of pathology can be directly compared to the result of the PMP test. The test is agnostic with respect to the underlying pathological mechanism, and therefore might be useful in identifying the involved segment(s) irrespective of the painful structure. METHODS: In 37 patients with confirmed IS (slippage 3-15mm), we compared sensitivity between the PMP test, the widely used provocative discography test and the discoblock test. RESULTS: The PMP test reliably identified the slip level in patients with IS, with sensitivity of 92%. Accepting the slipped disc as the origin of pain in IS, the sensitivity of the provocative discography and discoblock tests were 49% and 35%, respectively: i.e., too low to be contributive in clinical practice. CONCLUSIONS: The PMP test reliably identified the origin of localized pain in IS as the slip level, but should be used with care in CLBP patients in selecting discogenic pain patients for fusion surgery, since the specificity of the test is not known and it may be positive for any origin of localized pain.

Raman spectra of high- κ dielectric layers investigated with micro-Raman spectroscopy comparison with silicon dioxide.

Three samples with dielectric layers from high- κ dielectrics, hafnium oxide, gadolinium-silicon oxide, and lanthanum-lutetium oxide on silicon substrate were studied by Raman spectroscopy. The results obtained for high- κ dielectrics were compared with spectra recorded for silicon dioxide. Raman spectra suggest the similarity of gadolinium-silicon oxide and lanthanum-lutetium oxide to the bulk nondensified silicon dioxide. The temperature treatment of hafnium oxide shows the evolution of the structure of this material. Raman spectra recorded for as-deposited hafnium oxide are similar to the results obtained for silicon dioxide layer. After thermal treatment especially at higher temperatures (600°C and above), the structure of hafnium oxide becomes similar to the bulk non-densified silicon dioxide.

Contractile activity of human skeletal muscle cells prevents insulin resistance by inhibiting pro-inflammatory signalling pathways.

AIMS/HYPOTHESIS: Obesity is closely associated with muscle insulin resistance and is a major risk factor for the pathogenesis of type 2 diabetes. Regular physical activity not only prevents obesity, but also considerably improves insulin sensitivity and skeletal muscle metabolism. We sought to establish and characterise an in vitro model of human skeletal muscle contraction, with a view to directly studying the signalling pathways and mechanisms that are involved in the beneficial effects of muscle activity. METHODS: Contracting human skeletal muscle cell cultures were established by applying electrical pulse stimulation. To induce insulin resistance, skeletal muscle cells were incubated with human adipocyte-derived conditioned medium, monocyte chemotactic protein (MCP)-1 and chemerin. RESULTS: Similarly to in exercising skeletal muscle in vivo, electrical pulse stimulation induced contractile activity in human skeletal muscle cells, combined with the formation of sarcomeres, activation of AMP-activated protein kinase (AMPK) and increased IL-6 secretion. Insulin-stimulated glucose uptake was substantially elevated in contracting cells compared with control. The incubation of skeletal muscle cells with adipocyte-conditioned media, chemerin and MCP-1 significantly reduced the insulin-stimulated phosphorylation of Akt. This effect was abrogated by concomitant pulse stimulation of the cells. Additionally, pro-inflammatory signalling by adipocyte-derived factors was completely prevented by electrical pulse stimulation of the myotubes. CONCLUSIONS/INTERPRETATION: We showed that the effects of electrical pulse stimulation on skeletal muscle cells were similar to the effect of exercise on skeletal muscle in vivo in terms of enhanced AMPK activation and IL-6 secretion. In our model, muscle contractile activity eliminates insulin resistance by blocking pro-inflammatory signalling pathways. This novel model therefore provides a unique tool for investigating the molecular mechanisms that mediate the beneficial effects of muscle contraction.

Cannabinoid type 1 receptors in human skeletal muscle cells participate in the negative crosstalk between fat and muscle.

AIMS/HYPOTHESIS: Cannabinoid type 1 receptor (CB1R) antagonists such as rimonabant (Rim) represent a novel approach to treat obesity and related metabolic disorders. Recent data suggest that endocannabinoids are also produced by human adipocytes. Here we studied the potential involvement of endocannabinoids in the negative crosstalk between fat and muscle. METHODS: The protein level of CB1R in human skeletal muscle cells (SkM) during differentiation was analysed using western blotting. SkM were treated with adipocyte-conditioned medium (CM) or anandamide (AEA) in combination with the CB1R antagonists Rim or AM251, and insulin-stimulated Akt phosphorylation and glucose uptake were determined. Furthermore, signalling pathways of CB1R were investigated. RESULTS: We revealed an increase of CB1R protein in SkM during differentiation. Twenty-four hour incubation of SkM with CM or AEA impaired insulin-stimulated Akt(Ser473) phosphorylation by 60% and up to 40%, respectively. Pretreatment of cells with Rim or AM251 reduced the effect of CM by about one-half, while the effect of AEA could be prevented completely. The reduction of insulin-stimulated glucose uptake by CM was completely prevented by Rim. Short-time incubation with AEA activated extracellular regulated kinase 1/2 and p38 mitogen-activated protein kinase, and impaired insulin-stimulated Akt(Ser473) phosphorylation, but had no effect on Akt(Thr308) and glycogen synthase kinase 3alpha/beta phosphorylation. In addition, enhanced IRS-1 (Ser307) phosphorylation was observed. CONCLUSIONS/INTERPRETATION: Our results show that the CB1R system may play a role in the development of insulin resistance in human SkM. The results obtained with CM support the notion that adipocytes may secrete factors which are able to activate the CB1R. Furthermore, we identified two stress kinases in the signalling pathway of AEA and enhanced IRS-1(Ser307) phosphorylation, potentially underlying the development of insulin resistance.

Surface modification of titanium carbide with carbyne-containing nanocoatings.

The aim of this research is to investigate a novel approach to surface engineering of biomaterials that are based on transition metals of the groups IVA-VIA. The approach taken relies on the fact that, during the electropolishing of TiC surfaces, the removal of Ti atoms from the TiC surface surpasses that of C atoms. This leads to enrichment of the TiC surface with carbon. Transmission electron microscopic investigation showed that carbon-based films contain carbynes in the form of nanorod-like clusters with lengths in the range of 5-100 nm. This carbyne-containing layer is 50-100 nm thick. It was generalized that carbyne-containing nanofilms are formed on the carbide surface of transition metals of groups IVA-VIA during electropolishing. Since carbynes, being one-dimensional chain-like structures [(-C identical to C-)n/(=C=C=)n] with sp1 carbon-carbon hybridization, have the highest degree of biocompatibility because of their biological activity, the development of such surface bioengineering with carbynes extends applications of biomaterials based on transition metals of the groups IVA-VIA.

Risk in numbers--difficulties in the transformation of genetic knowledge from research to people--the case of hereditary cancer.

Difficulties in communicating diagnostic information are exacerbated when the 'diagnosis' is a 'genetic risk' for cancer. The risk estimation demanded in this situation differs from other types of probability estimations. Observations of participants in 45 consultation sessions between physicians and potential patients were conducted at a clinic for hereditary cancer to explore the communication of genetic information. Thirty-three sessions were audiotaped, transcribed verbatim and analyzed, along with notes from the other sessions. A dominant theme was found to be numerical discussion of risk. Further analysis resulted in the description of problems for practitioners in the process of translating scientific knowledge into clinical management. Problems in providing information include unclear aims of the consultation sessions, mixing various types of background information and probabilities, recognizing how low the predictive values are, and difficulties in communicating the relationship between probability and conclusions. Problems in communicating information about the genetic risk for cancer are of at least two types: dilemmas arising from uncertainties implicit in the nature of the information itself and difficulties in communicating information in a manner that those concerned can interpret. These issues need clarification, so that information with far-reaching consequences can be made as clear and comprehensible as possible for those involved.

[Count on your beliefs. Bayes--not the P value--measures credence]. / Räkna med vad du tror. Bayes--inte P-värdet--mäter tilltron.

This article (the second of two) describes traditional (frequentistic) statistical analysis in the context of the confidence interval. Bayesian analysis is described in two settings. In the choice between diagnostic alternatives, the bayesian approach offers useful integration of new information with previous knowledge. With regard to the evaluation of clinical trial data, this article exemplifies bayesian analysis as contrasted with traditional analysis, and advantages of the former are cited. A brief literature review exposes the wide applicability of bayesian analysis in medical statistics.

[Count on your beliefs. Bayes' theorem in diagnosis]. / Räkna med vad du tror. Bayes' sats i diagnostiken.

Bayesian analysis of data finds increasing use in medical statistics, diagnostic evaluation and decision analysis. The central element in bayesian analysis is a set of mathematical rules for integrated evaluation of prior knowledge and new information. In many situations this approach has superior ability to deliver dependable updated knowledge and to provide an optimal probability basis for decisions. This article (the first of two) presents Bayes' theorem and its application in diagnostic work. It is explained how likelihood ratios of diagnostic tests interact with the outcome of such tests in the conversion of initial information (prior odds) to enhanced information (posterior odds).

Reproducibility of tumor response evaluation in patients with high-grade malignant non-Hodgkin's lymphoma.

Estimation of complete response (CR) and partial response (PR) in patients with non-Hodgkin's lymphoma (NHL) is associated with a number of potential sources of error. The aim of this study was to define the reproducibility of response evaluation performed by an independent review committee (RC). In a phase III study of patients >60 yr with aggressive NHL, 60 patients who were already evaluated by the independent review committee (RC 1) for response were randomized to three groups and re-evaluated (RC 2). The assessment was classified into one of seven mutually exclusive categories, where the important borderlines with regard to one of the major end-points of the study, the CR rate, were between CR, "CR uncertain" (CR(U)), and PR. A discrepancy between RC 1 and 2 was found in 8/60 patients (13.3%), influencing the CR/CR(U) status in four of these patients. Two CR and two PR patients were reclassified as CR(U). Thus, CR/CR(U) was changed in 4/60 (6.7%). The reports of the local investigators were compared with that of RC 1 in 254 patients. The CR/CR(U) status was affected in 41 of these patients (16.1%). It is concluded that an independent RC is a major prerequisite for a uniform response evaluation in phase III clinical trials. However, the good RC reproducibility does not motivate a second assessment. Moreover, in the phase III setting end-points other than the CR rate, such as time to treatment failure, cause specific and overall survival are preferred.

Interchangeability of ambulatory and office blood pressure: limitations of reproducibility and agreement.

A possible equivalence of office (Off) patient-recorded blood pressure (BP) and ambulatory (Amb) BP was evaluated. The criteria were the between-visits reproducibility (R) of oscillometrically measured supine office (Off), seated Off, and 24-h Amb BP and the agreement between Off and Amb data. Randomly ordered sessions were completed within 4 months in 59 untreated patients with Amb 24-h BP 136/87 (SD 14/10) mmHg and HR 72 (SD 9). R improves as SD of differences between sessions decreases with the number (n) of values included in the average so that SDD = a n(-b), where a and b are constants for each method, data sampling strategy, and group. R of a few steady Off data is better than R of a few Amb data. As n of the averaged values increases, R of Off and Amb methods converges and with n approximately 24 becomes identical. Only further increase in n of Amb data makes R of the Amb method superior than the Off method. The variably elevated initial Off BP distorts R and agreement. After approximately 6 readings, Off BP stabilizes at a lower "steady" level. "Steady" data averaged over visits are close to the Amb 24-h average from two sessions. Supine Off "steady" level is close to supine levels before sleep. The Off versus Amb method agreement improves by averaging "steady" BP from one up to four Off sessions, up to 7 "steady" Off readings over a session, and BP in both arms. At best the SBP agreement is within +/- 7.6 mmHg in 90% of cases with 24-h Amb S/D BP ranging 115-155/75-105 mmHg. The casually elevated BP can be evaluated only by the demonstrated between-visits reproducible 24-h Amb average or by the nearly equivalent average of multiple "steady" data from two to four Off visits.

Numerical modeling of the temperature distribution within a bonded paper web when undergoing microwave heating in a waveguide

In this paper, a numerical technique is used to study the temperature distribution within the heated bonded paper web placed in a waveguide. The parameters of the problem were selected so as to best locate the test sample that would generate the desired absorbed power. The method of false transient was utilized to accelerate the numerical convergence and the equations were discretized with central difference in both time and space. The resulting system of equations was solved using an Alternating Direction Implicit scheme. Good agreement was achieved between the numerical solutions and the experimental validations.

Classification of thyroid size by palpation and ultrasonography in field surveys.

BACKGROUND: Goitre surveys are used to assess the degree of iodine deficiency in a population. The change of goitre classification made by WHO in 1994 implied that a smaller thyroid size should be regarded as goitre. Furthermore, the acceptable goitre prevalence was lowered from 10% to 5%, and ultrasonography was recommended as a more precise method for diagnosis of goitre. We studied the effects of the change of palpation system, and compared the precision of the old and new systems with that of ultrasonographic examination. METHODS: We studied 225 schoolchildren (aged 7-14 years) in a highland village in Tanzania. The size of the thyroid was assessed in duplicate by ultrasonography and by WHO's 1960 and 1994 palpation systems. The latter were done by three examiners. Variations within and between examination methods and examiners were assessed, and measurement errors by ultrasonography were assessed from duplicate examinations. The sensitivity and specificity of the two palpation systems were calculated, with diagnosis by ultrasonography as the gold standard. Apparent palpation prevalences were calculated at a "true" 5% prevalence. FINDINGS: The lowered criterion for goitre resulted in an extra 20-33% of children being diagnosed as having goitre by palpation. The variation between repeat examinations was only slightly smaller by ultrasonography (kappa=0.63) than by experienced examiners (kappa=0.57-0.58). The variation between thyroid volume estimation by ultrasonography and the true volume was about 50% due to both measurement error and variation in the shape of thyroid lobes. The new goitre criterion decreased specificity from 76% to 29%, whereas sensitivity rose from 56% to 80%. In contrast, a suggested sharpening of the old criterion increased specificity to 90%. INTERPRETATION: A return to the old (1960) palpation criterion for goitre: "lobes larger than the terminal phalanxes of thumbs" and to an accepted palpation goitre prevalence of 10% can allow affordable monitoring of thyroid size through palpation in field surveys.

Collegial disagreements over appropriate palliative care: a case study.

The appropriate limit or scope of investigation and treatment of the palliative patient is an evolving and still controversial area. Major differences of opinion persist. This case report highlights such differences. The ethics of decision-making in palliative care are discussed and a series of practical steps that may help in these dilemmas is briefly highlighted.