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.

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.

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.

Graves' hyperthyroidism: treatment with antithyroid drugs, surgery, or radioiodine--a prospective, randomized study. Thyroid Study Group.

To analyze the benefits and risks of three common treatments, we randomly assigned 179 patients with Graves' hyperthyroidism as follows: 60 patients, 20-34 yr of age (young adults), received antithyroid drugs for 18 months (medical) or subtotal thyroidectomy (surgical), and 119 patients, 35-55 yr of age (old adults), received medical, surgical, or radioiodine (iodine-131) treatment. The follow-up time was at least 48 months. Antithyroid drugs, surgery, or iodine-131 treatment normalized the mean serum hormone levels within 6 weeks. The risk of relapse was highest in the medically treated young and old adults (42% vs. 34%), followed by that in those treated with iodine-131 (21%) and that in the surgically treated young and old adults (3% vs 8%), respectively. Elevated TSH receptor antibodies at the end of medical therapy or increasing TSH receptor antibodies values after medical or surgical treatment increased the probability of relapse. Development or worsening of ophthalmopathy was not associated with relapse per se. Ninety percent of the subjects in all groups were satisfied with the treatment they received. No significant difference in sick-leave due to Graves' or other diseases was seen during the first 2 yr after initiation of therapy. The increased risk of ophthalmopathy in patients with high serum T3 levels, especially when treated with iodine-131, and the relatively high frequency of relapse after treatment with antithyroid drugs are important factors to consider when selecting therapy for Graves' disease.

Prevalence of sleep apnea syndrome among Swedish men--an epidemiological study.

The prevalence of the sleep apnea syndrome (SAS) among Swedish men 30-69 years old was estimated by a two-stage procedure. In the first stage, 4064 questionnaires were mailed to a random sample of a defined population in the municipality of Uppsala. The response rate was almost 80%; 15.6% of the responders were habitual snorers and 5.8% complained of daytime sleepiness. From these, a group of 166 men highly suspected of having SAS was selected. Eventually, 61 of these came for all-night polysomnographic studies, and 15 of these were found to have SAS. On this basis the lower limit of the prevalence of SAS was estimated to be as high as 1.3%. The majority of subjects with the syndrome were in the age group 50-59 years.

A 10-year follow-up of snoring in men.

STUDY OBJECTIVES: Little is known about the natural development of snoring, and this survey was conducted to study the development of snoring in men over a 10-year period. DESIGN: Population-based prospective survey. SETTING: The Municipality of Uppsala, Sweden. PARTICIPANTS AND MEASUREMENTS: In 1984, 3,201 randomly selected men aged 30 to 69 years answered a questionnaire on snoring and sleep disturbances. Of the 2,975 survivors in 1994, 2,668 (89.7%) answered a new questionnaire with identical questions to those used at baseline. Questions about smoking habits, alcohol, and physical activity were also added. RESULTS: Habitual snoring was reported by 393 men (15.0%) in 1984 and by 529 (20.4%) 10 years later. In both 1984 and 1994, the prevalence of snoring increased until age 50 to 60 years and then decreased. Risk factors for being a habitual snorer at the follow-up were investigated using multiple logistic regression with adjustments for previous snoring status, age, body mass index (BMI), weight gain, smoking habits, and physical activity. In men aged 30 to 49 years at baseline, the predictors of habitual snoring at the follow-up, in addition to previous snoring status, were as follows: persistent smoking (adjusted odds ratio, 95% confidence interval) (1.4, 1.1 to 1.9), BMI 1984 (1.1, 1.02 to 1.1/kg/m2) and weight gain (1.1, 1.03 to 1.2/kg/m2). Among men aged 50 to 69 years, after adjustments for previous snoring status and age, weight gain was the only significant risk factor for developing habitual snoring (1.2, 1.05 to 1.4/kg/m2). CONCLUSIONS: In men, the prevalence of snoring increases up to the age of 50 to 60 years and is then followed by a decrease. Weight gain is a risk factor for snoring in all age groups, while smoking is mainly associated with snoring in men <60 years of age.

Pulmonary function after autologous bone marrow transplantation in children.

Forty-two children receiving bone marrow autografts were studied prospectively regarding acute pulmonary complications; there was no procedure-related mortality and only one case of interstitial pneumonitis. An analysis was also made of the pulmonary function tests (PFTs) of the 27 autografted children who were disease-free and had been followed up for at least 1 year (median 4.1 years, range 1.1-7.6 years). PFTs were performed before and 6, 12, 24, 36 and 60 months after autologous BMT. The mean pre-transplant values of total lung capacity (TLC), vital capacity (VC) and forced expiratory volume in one second (FEV1) were close to predicted but 6 months after autologous BMT there was a statistically significant decrease (11, 13 and 15% below baseline, respectively) in patients receiving total body irradiation in their conditioning regimen. There was some but not complete recovery with time. DLCO remained low throughout the study, irrespective of the conditioning regimen. In summary, acute pulmonary complications were few and PFTs showed only modest changes from baseline after ABMT. At the latest follow-up no respiratory symptoms had reportedly occurred in any of the children and the chest radiographs were normal. Although the results are promising so far, long-term follow-up is necessary to evaluate the final outcome in these children.

Analysis and presentation. Clinical trials on prostate cancer.

OBJECTIVE: To present guidelines for the analysis and presentation of clinical trials on prostate cancer. METHODS: Textbooks in statistics and oncology were searched for information, as were separate articles on the topic. Previously published advice was fused with own experience. RESULTS: Minimum key points are given for the sections: Introduction, Materials and Methods, Results, Discussion, and Summary. The importance of 1 primary question in any clinical trial is stressed. The value of a detailed presentation of the trial design, the patient population and the inclusion/exclusion criteria, the characterization of the disease, the treatment schedules, and toxicity is underlined. Application of various statistical methods for different endpoints is suggested. Maturity of data, time for publication, and avoidance of publication bias are discussed. Some common pitfalls in the statistical analyses of clinical results are indicated. The impact of prognostic factors, proper staging procedures, and secondary treatments on the interpretation of survival analysis is pointed out. A shift from the (mis-)use of the P value in favor of confidence intervals is strongly encouraged. The use of comparing the survival of responders versus nonresponders is to be abandoned. A few practical hints concerning the presentation are offered. The minimum of data that should be presented in absolute numbers is indicated. Also, the data that should be provided in both graphic and numeric format are exemplified. Examples of essential graphic illustrations are provided. The need for improvements in the design analysis, and presentation of clinical trials is reemphasized. Finally, numerous references are listed. The article is addressed not only to authors and readers of clinical trials, but also to editors of medical journals. CONCLUSION: The suggested guidelines may be useful in the analysis, presentation, and interpretation of clinical trials on prostate cancer. Moreover, compliance with these guidelines may facilitate comparisons with other similar trials and also, the incorporation of single studies into metaanalyses.

Pharmacokinetics of high-dose busulphan in relation to age and chronopharmacology.

Busulphan levels in plasma were measured in 27 patients during conditioning therapy (1 mg/kg x 4 for 4 days) before bone marrow transplantation. The mean minimal concentration found in children aged less than 5 years (237 ng ml-1) was lower than that observed in adults or older children (607 and 573 ng ml-1, respectively). The AUC for the last dose was significantly lower in young children (2.315 h ng ml-1) than in adults or older children (6,134 and 5,937 h ng ml-1, respectively). The elimination half-life for the last dose in young children was shorter (2.05 h) than that in either adults (2.59 h) or older children (2.79 h). When the AUC was normalized for body surface area, the difference between young children and the other groups was smaller but remained statistically significant. The total body clearance was significantly higher in young children (7.3 ml min-1 kg-1) as compared with both older children and adults (3.02 and 2.7 ml min-1 kg-1, respectively). The plasma levels of busulphan showed circadian rhythmicity, especially in young children. The concentration measured during the night in some patients was up to 3-fold that observed during daytime. We conclude that the busulphan dosage for children must be reconsidered and that further studies are urgently needed to develop an optimal therapy.

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.

Is a "palliative" patient always a palliative patient? Two case studies.

Review of the literature suggests that misdiagnosis of terminal illness is infrequent. In the first 6 months of the recently established Edmonton Regional Palliative Care Program, two of 330 referrals proved to be in the category of erroneous diagnosis of terminal disease. These two cases are reported, along with discussion of aspects of the time-honored usefulness of careful history and physical examination. This experience highlights the importance of assessment, investigation, and aggressive therapy, even in "terminal" patients, including those in the geriatric population.

Initial demographic, symptom, and medication profiles in patients admitted to continuing palliative care units.

We retrospectively reviewed 110 consecutive admissions to continuing palliative care units, which were designed as part of a regionalized, comprehensive palliative care program in Edmonton, Canada. Ninety-six patient charts met the criteria for evaluation. Demographic characteristics, and, when available, symptom profiles, cognitive status, and risk for a history of substance abuse were described. The medications on admission were tabulated, and in those 93 patients who had consults done by a palliative care consultant, these are compared to recommended medications. This study showed an older cohort of patient (mean +/- SD = 75 +/- 11 years) than had previously been described in a tertiary unit in the same community. Median length of stay was 21 days (range, 0-> 200 days). Cognitive impairment was higher than would be anticipated on the basis of age alone, with 32/47 [64% (confidence interval (CI) 55%-81%)] of patients who had had cognitive testing done on the day of consult being found to be cognitively impaired. Symptoms, as measured by the Edmonton Symptom Assessment Scale, were similar to those found for patients admitted to the tertiary palliative care unit. In the 93 patients who had palliative care consults done on admission, there were a total of 179 recommendations for medication or hydration changes. Overall compliance with these recommendations was 84% (CI, 79%-89%). The highest compliance was observed for recommendations to start hydration clysis [27/27, 100% (CI, 100%)], and the lowest rate was observed for altering or decreasing hypnotic medications [11/22, 50% (CI, 29%-71%)]. We conclude that the patients were of higher acuity than anticipated.

Quality of life aspects and costs in treatment of Graves' hyperthyroidism with antithyroid drugs, surgery, or radioiodine: results from a prospective, randomized study.

The patients' views and costs of three different forms of treatment for Graves' hyperthyroidism were investigated. The study comprises 174 patients with Graves' hyperthyroidism who were stratified into two age groups: 20 to 34 years and 35 to 55 years. The younger group was randomly assigned to treatment with antithyroid drug plus thyroxine for 18 months or subtotal thyroidectomy, and in the older group iodine-131 was added as a third alternative. The patients' views of their therapy were based on a questionnaire formulated to identify possible differences between the three treatment forms. The costs were assessed by analyzing the official hospital reimbursement system for both outpatient and inpatient costs for a period of 2 years from the day of randomization. The results show that no significant differences in opinion were found between the five treatment groups with regard to any of the questions. Furthermore, only 10% of the patients expressed slight and 3% major hesitation to recommend the treatment form received to a friend with similar disease. Twenty percent of the patients with endocrine ophthalmopathy reported the eye problems to be much more troublesome and 14% somewhat more troublesome than the thyroid problems. The cost proportion between the medical and surgical treatment in the young group was 1:2.5 (1 = 1126 United States dollars [USD]) before and 1:1.3 (1 = 2284 USD) after inclusion of the relapse costs. The proportion between the medical, surgical, and iodine-131 treatment in the older group was 1:2.5:1.6 (1 = 1164 USD) before and 1:1.6:1.4 (1 = 1972 USD) after inclusion of the relapse costs.

Suramin inhibits the growth of human breast cancer cell lines. Studies on parental lines and corresponding sublines with acquired doxorubicin resistance with and without expression of P-glycoprotein.

Suramin at 100 to 800 micrograms/ml caused a dose dependent growth inhibition in three (Zr-75-1, BT 549 and HS-578T) parental human breast cancer cell lines and their corresponding sublines with acquired doxorubicin (dox) and multi-drug resistance. The effect was significantly more marked after 7 days suramin exposure compared with 3 days. The oestrogen and progesterone receptor rich cell line Zr-75-1 was more responsive to suramin compared with the other two lines. The sublines Zr-75-1-dox and HS-578T-dox with an increased expression of the permeability glycoprotein (P-gp) demonstrated a significantly decreased cell survival compared with corresponding parental cell lines at 3 and 7 days exposure of suramin, respectively. The subline BT 549-dox with multi-drug resistance without P-gp expression had a significantly impaired response after 3 days suramin compared with the parental line. These results indicate that suramin may be a potential therapeutic agent for the breast cancer patients with P-gp expression and multi-drug resistance.

Self-reported symptom distress in cancer patients: reflections of disease, illness or sickness?

This article examines the relationships between symptom distress in a heterogeneous group of cancer patients and a number of possible explanatory variables, categorized as demographic, medical/clinical, individual/psychosocial and variables related to patients' views of care provided by the health care system. A series of explorative multiple regression analyses were undertaken to this end. The data are derived from a cross-sectional study of cancer patients diagnosed in 1987 at one general hospital in the greater Stockholm area, using semi-structured interviews in conjunction with McCorkle and Young's Symptom Distress Scale, Antonovsky's Sense of Coherence Questionnaire, Cutrona and Russell's Social Provisions Scale and Smilkstein's Family APGAR. Symptom distress is studied as a cumulative index, as well as in terms of the sub-indexes of pain, appetite/nausea, functional aspects, psychological aspects and social aspects. When the four categories of explanatory variables are combined, considerably higher levels of variance are explained for all 6 indexes of the Symptom Distress Scale, than when the regression analyses are performed separately with each distinct category of explanatory variables. This provides a statistical illustration of the multifaceted and complex nature of symptom distress. The data are presented in the context of a conceptual discussion about the meaning of symptoms. Symptom distress, in this study, appears to reflect both personal and cultural experiences, that is 'illness' and 'sickness' processes, rather than primarily medical/clinical variables, or 'disease'. Antonovsky's salutogenic model is suggested as a fruitful framework for further analysis.

Immunohistochemical detection of CA-125 and carcinoembryonic antigen in ovarian tumors in relation to corresponding preoperative serum levels.

The immunohistochemically detectable expression of CA-125 and CEA in ovarian tumor tissue from 187 patients was related to corresponding preoperative serum levels. A strong positive association between tissue expression and the serum level of both the CA-125 and CEA antigens was found in cases of invasive epithelial ovarian carcinoma. However, this relationship was absent for CA-125 in borderline cases and patients with benign ovarian tumors, although the antigen frequently was detectable in them. The presence of ascites could be verified in 3 of 10 cases with benign CA-125 negative tumors, but elevated CA-125 levels in serum. 'False negative' CA-125 levels were found in 6 borderline and 7 true invasive carcinoma cases despite positive tissue staining. Eight of those patients had limited stage I disease. The data suggests that although the tissue expression of the CA-125 and CEA antigens in invasive ovarian carcinoma has an important influence in the corresponding serum level, compartment barriers and low cell turnover in benign, and to a lesser extent borderline, cases result in low serum levels. In addition, other factors influence serum levels of CA-125, such as secondary peritoneal response with or without ascites, which may cause 'falsely elevated' CA-125 results in benign disease.

Tissue expression of CA-125 and carcinoembryonic antigen in ovarian carcinoma in relation to nuclear DNA content, histologic grade, and patient survival.

In a prospective study the immunohistochemically detectable tissue expression of the antigens CA-125 and CEA in 112 epithelial ovarian carcinomas and 23 borderline tumors was related to histologic features of the tumor and to patient survival. The CA-125 antigen was expressed mainly in non-mucinous tumors, with no evident association between histologic grade and immunoreactivity. CEA was expressed in mucinous tumors regardless of tumor grade. Flow cytometric DNA analysis was performed on fresh frozen tissue in a subgroup of 60 cases. There was no association between DNA ploidy or S-phase fraction and the CA-125 or CEA antigen expression. Tumor stage, size of residual tumor masses after surgery and DNA ploidy had independent associations with patient survival in multivariate log-rank analysis of prognostic factors. However, there was no association between the CA-125 or CEA antigen expression and patient survival. Thus, in ovarian carcinoma the expression of the CA-125 and CEA antigens seems to be independent of the inherent malignant potential of the tumor epithelium, while DNA analysis provides valuable prognostic information.

Interexaminer reliability in physical examination of patients with low back pain.

STUDY DESIGN: Seventy-one patients with low back pain were examined by two physiotherapists (50 patients) and two physicians (21 patients). The two physiotherapists had worked together for many years, but the two physicians had not. The interexaminer reliability of the clinical tests included in the physical examination was evaluated. OBJECTIVES: To evaluate the interexaminer reliability of clinical tests used in the physical examination of patients with low back pain under ideal circumstances, which was the case for the physiotherapists. SUMMARY OF BACKGROUND DATA: Numerous clinical tests are used in the evaluation of patients with low back pain. To reach the correct diagnosis, only tests with an acceptable validity and reliability should be used. Previous studies have mainly shown low reliability. It is important that clinical tests not be rejected because of low reliability caused by differences between examiners in performance of the examination and in their definition of normal results. METHODS: Two examiners, either two physiotherapists or two physicians, independently examined patients with low back pain. RESULTS: In approximately half of the clinical tests studied, an acceptable reliability was demonstrated. CONCLUSION: On the basis of the physiotherapists series, the reliability was acceptable for a number of clinical tests that are used in the evaluation of patients with low back pain. The results suggest that clinical tests should be standardized to a much higher degree than they are today.

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.