One-year-survey with multicenter data of more than 4,500 patients with degenerative rheumatic diseases treated with therapeutic nuclear magnetic resonance.

BACKGROUND AND OBJECTIVES: Nuclear magnetic resonance (NMR) has been shown to stimulate repair processes and cartilage and to influence pain signalling. It represents an alternative therapy for patients suffering from osteoarthritis (OA). To prove the clinical success of this new therapeutical method, validated measuring parameters are important that are convincing for pain and function in a one-year-follow-up. METHODS: During the course of its application over the last 10 years, over 4,500 protocols of a one-year-follow-up have been collected to record the outcome of NMR therapy. This report reflects the outcome of NMR therapy on patients with the following degenerative rheumatic diseases: OA of the knee (n = 2.770), OA of the hip (n = 673), OA of the ankle joint (n = 420) and chronic low back pain (n = 655). Data were collected at baseline, 6­8 weeks and 6 and 12 months following NMR treatment. RESULTS: Pain was reduced significantly 6 weeks after NMR treatment in the cases of all four examined indications and stayed measurably reduced up to 6 and 12 months. The improvements in all three forms of pain (pain on load, pain on motion, pain at rest) following NMR treatment were around 21­50% on average. CONCLUSIONS: Following therapy with NMR, patients with OA of all four types experienced a distinct improvement in their ability in functional parameters. Overall, the 10 years of a one-year-survey with multicenter data gathered on the effect of NMR therapy on patients verifiably proved its efficacy amongst patients with degenerative rheumatic diseases.

Impact of international consensus guidelines on antiviral therapy of chronic hepatitis C patients in Switzerland.

AIM OF THE STUDY: To assess the impact of international consensus conference guidelines on the attitude of Swiss specialists when facing the decision to treat chronic hepatitis C patients. METHODS: Questionnaires focusing on the personal situation and treatment decisions were mailed to 165 patients who were newly diagnosed with hepatitis C virus (HCV) infection and enrolled into the Swiss Hepatitis C Cohort Study during the years 2002-2004. RESULTS: Survey respondents (n = 86, 52.1%) were comparable to non-respondents with respect to severity of liver disease, history of substance abuse and psychiatric co-morbidities. Seventy percent of survey respondents reported having been offered antiviral treatment. Patients deferred from treatment had less advanced liver fibrosis, were more frequently infected with HCV genotypes 1 or 4 and presented more often with a history of depression. There were no differences regarding age, socio-economic background, alcohol abuse, intravenous drug abuse or methadone treatment when compared with patients to whom treatment was proposed. Ninety percent of eligible patients agreed to undergo treatment. Overall, 54.6% of respondents and 78.3% of those considered eligible had actually received antiviral therapy by 2007. Ninety-five percent of patients reported high satisfaction with their own hepatitis C management. CONCLUSIONS: Consistent with latest international consensus guidelines, patients enrolled in the Swiss Hepatitis C Cohort with a history of substance abuse were not withheld antiviral treatment. A multidisciplinary approach is warranted to provide antiviral treatment to patients suffering from depression.

Host- rather than virus-related factors reduce health-related quality of life in hepatitis C virus infection.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with decreased health-related quality of life (HRQOL). Although HCV has been suggested to directly impair neuropsychiatric functions, other factors may also play a role. PATIENTS AND METHODS: In this cross-sectional study, we assessed the impact of various host-, disease- and virus-related factors on HRQOL in a large, unselected population of anti-HCV-positive subjects. All individuals (n = 1736) enrolled in the Swiss Hepatitis C Cohort Study (SCCS) were asked to complete the Short Form 36 (SF-36) and the Hospital Anxiety Depression Scale (HADS). RESULTS: 833 patients (48%) returned the questionnaires. Survey participants had significantly worse scores in both assessment instruments when compared to a general population. By multivariable analysis, reduced HRQOL (mental and physical summary scores of SF-36) was independently associated with income. In addition, a low physical summary score was associated with age and diabetes, whereas a low mental summary score was associated with intravenous drug use. HADS anxiety and depression scores were independently associated with income and intravenous drug use. In addition, HADS depression score was associated with diabetes. None of the SF-36 or HADS scores correlated with either the presence or the level of serum HCV RNA. In particular, SF-36 and HADS scores were comparable in 555 HCV RNA-positive and 262 HCV RNA-negative individuals. CONCLUSIONS: Anti-HCV-positive subjects have decreased HRQOL compared to controls. The magnitude of this decrease was clinically important for the SF-36 vitality score. Host and environmental, rather than viral factors, seem to impact on HRQOL level.

Intravascular brachytherapy: a systematic review of its role in reducing restenosis after endovascular treatment in peripheral arterial disease.

INTRODUCTION: Intravascular brachytherapy (IVBT) utilises the percutaneous insertion of a radioactive source to inhibit myointimal hyperplasia in arteries treated by balloon angioplasty or stenting. A systematic review was performed of trials of IVBT in patients with Peripheral Arterial Disease (PAD). METHODS: Search strategy - the reviewers searched Medline, Embase, the Cochrane Peripheral Vascular Diseases Group trials register, DARE, CCT and NHS EED for clinical studies and trials of adjuvant IVBT in PAD. Two reviewers assessed trial quality independently. RESULTS: Fourteen clinical trials were identified by the search, representing five clinical studies (all allocated D for not randomised) and one randomised controlled trial (allocated A). The randomised trial showed a benefit for IVBT compared with placebo (OR 0.35, 95% CI 0.24-0.53). In the non-randomised studies, 12 month cumulative patency rates ranged from 60-87%. There were few technical complications. In the only report involving IVBT and routine concurrent stent insertion acute thrombosis occurred in 7 (21%) of patients. CONCLUSION: Early reports have confirmed the safety and technical feasibility of IVBT. However, follow-up is too short at present to assess the durability and long-term complications of this new therapeutic option.

Intravascular brachytherapy for peripheral vascular disease.

BACKGROUND: International treatment of atherosclerotic narrowed and blocked arteries involves either bypassing the blockage using a graft, widening it from the inside with a balloon, a procedure known as percutaneous transluminal angioplasty (PTA), or providing a strut to hold the vessel open, known as a stent. All of these treatments are however limited by the high numbers that fail within a year. Intravascular brachytherapy (IVBT) is the application of radiation directly to the site of vessel narrowing. It is known to inhibit the processes that lead to restenosis (narrowing) of vessels and grafts after treatment. OBJECTIVES: The objective of this review was to assess the efficacy and complications of intravascular brachytherapy on maintaining patency after angioplasty or stent insertion in native vessels or bypass grafts of the iliac or infrainguinal arteries. SEARCH STRATEGY: The reviewers searched the Cochrane Peripheral Vascular Diseases Group Trials Register (last searched 5 July 2002), the Cochrane Controlled Trials Register (last searched Issue 2, 2002), MEDLINE, EMBASE and reference lists of relevant articles. SELECTION CRITERIA: Randomised trials of the use of brachytherapy as an adjunct to the treatment of patients with peripheral arterial diseases (PAD) or stenosed bypass grafts of the iliac or infrainguinal arteries arteries versus the procedure without brachytherapy. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Adverse events information was collected from the trials. MAIN RESULTS: One trial was identified which met the inclusion criteria, involving 117 patients, mean age 71 years (43-89). The trial compared PTA versus PTA and IVBT in patients with long-segment de novo or restenotic lesions or occlusions of any length in the femoropopliteal artery. Results were provided at six month follow up in 107 patients (54 PTA alone, 53 PTA+IVBT). The results favoured adjuvant IVBT in preventing restenosis/occlusion with an odds ratio (OR) of 0.35 (95% CI 0.24 to 0.53). Analysis of subgroups showed a significant benefit of IVBT in non-diabetics, OR 0.22 (95% CI 0.07 to 0.69), in those undergoing IVBT in restenotic lesions, OR 0.32 (95% CI 0.10 to 1.01), occlusive lesions, OR 0.19 (95% CI 0.06 to 0.62) and lesions in which the PTA length was greater than 10cm, OR 0.24 (95% CI 0.09 to 0.62). REVIEWER'S CONCLUSIONS: Results from the only trial available would suggest that IVBT is effective at improving the patency of femoropopliteal arteries undergoing PTA in the short-term, particularly in non-diabetics with long occlusions (>10cm).

The modulation by 3,5,3'-triiodothyronine (T3) of pituitary T3 nuclear receptors in hypothyroid rats is inhibited by cycloheximide.

The density of T3 nuclear receptors is known to vary with tissues and physiopathological conditions, but the factors involved in their regulation are still unknown. We have previously shown in the anterior pituitary gland that T3 modulates its own receptors; the density of T3 receptors in hypothyroid rats is half that in normal rats, and one injection of T3 is able to restore normal density of T3 receptors within 1-3 h. To determine whether T3 has a direct action on the synthesis of its nuclear receptor, the effect of cycloheximide (Cy) on T3-induced nuclear receptor was studied. In addition, the relationship between the density of pituitary T3 receptors and the secretion of TSH in different thyroid states was examined. In normal rats one injection of Cy (0.5-8 mg/100 mg BW) induced within 3 h a dose-dependent reduction in the density of pituitary T3 receptors as well as an important decrease in plasma TSH, with no changes in T4, T3, or pituitary TSH content. In hypothyroid rats the 50% decrease in the density of pituitary T3 receptors was not further reduced by 1 mg Cy. However, when the same dose of Cy was given 30 min before T3 it completely inhibited the induction by T3 of its receptors. When Cy was given 30 min or 1 h after T3 the inhibition was only partial. An inverse correlation was found between the density of T3 receptors in the pituitary gland and plasma TSH (r = -0.8128) in all experimental groups except those treated with Cy; this drug had an inhibitory effect on both TSH secretion and the density of receptors. The present data, therefore, support the view that T3 in the pituitary gland may induce the synthesis of its own nuclear receptors and that the density of T3 receptors is also involved in the control of TSH secretion.

[Effect of cycloheximide on nuclear triiodothyronine receptors in the pituitary of the normal and hypothyroid rat]. / Effet du cycloheximide sur les récepteurs nucléaires de la triiodothyronine dans l'hypophyse du rat normal et hypothyroidien.

Cycloheximide (Cy), an inhibitor of protein synthesis was found to provoke a dose-dependent decrease of the hypophysis T3 nuclear receptors (T3nR) concentration in normal rats. In thyroidectomized rats, the reduced T3nR density was found to be normalized within 3 hrs. after a single injection of T3. Pretreatment with Cy inhibited the T3 effect on its own receptors, whereas Cy given after T3 was partially or not effective. These data suggest that the half-life of T3nR in the hypophysis is short (about 3 hrs.), and that it depends on protein neosynthesis.

Modulation of thyroid hormone nuclear receptor levels by L-triiodothyronine (T3) in the rat pituitary.

The concentration of thyroid hormone nuclear receptors varies from one tissue to another, the anterior pituitary (AP) gland possessing the highest. Since 3,5,3',1-triiodothyronine (T3) controls within a narrow range the secretion of TSH from the pituitary gland, this study was carried out to establish whether T3 modulates its own pituitary nuclear receptors and if so, whether this modulation is correlated with the thyroidal status and TSH secretion. Salt-solubilized T3 nuclear receptors were measured in the AP gland of thyroidectomized and intact adult male rats as well as in thyroidectomized rats treated with T3. In intact male rats the maximum binding capacity of pituitary T3 nuclear receptors (MBC-T3nR), determined by Scatchard analysis, was 578 +/- 45 fmoles T3/mg protein or 27 +/- 3 fmoles T3/AP (mean +/- SEM, n = 19). 2 weeks after thyroidectomy there was a marked decrease in serum T3 and T4 concentrations as well as in the MBC-T3nR (231 +/- 26 fmoles T3/mg protein or 9.3 +/- 1.2 fmoles T3/AP, n = 7) which was still observed 8 and 16 weeks after thyroidectomy. The affinity constant (Ka) of T3 for its pituitary nuclear receptors was significantly greater in thyroidectomized rats than in intact rats (3.61 +/- 0.70 vs. 1.09 +/- 0.15 X 10(10) M-1, P less than 0.001). To test whether treatment with T3 would restore a normal MBC-T3nR, 2-week thyroidectomized rats were injected with T3(0.5 micrograms/100 g b.w.) and killed 10 min, 1, 3, 15 or 24 h after T3 injection. 10 min after T3 injection MBC-T3nR was not altered but it returned to normal values 1 h after injection (441 +/- 97 fmoles T3/mg protein) and was maintained so for at least 3 h. 15 h after T3 injection MBC-T3nR was again decreased in spite of serum T3 levels that were twice as high as in normal rats. In contrast, when T3 was injected at the dose of 1.0 micrograms/100 g b.w. the MBC-T3nR was maintained within the normal range as long as 24 h after the injection (428 +/- 125 fmoles T3/mg protein) with serum T3 concentrations that were twice the normal levels (1.27 +/- 0.06 vs. 0.67 +/- 0.01 ng/ml). These results support the hypothesis that T3 modulates the concentration of its own nuclear receptors in the rat pituitary gland. The absence of any effect of T3 10 min after injection is suggestive of an effect of T3 on the synthesis of its receptors rather than on an alteration of unoccupied receptors that would require T3 for adequate configuration and detection. This modulation of pituitary T3 receptors by T3 may provide an additional mechanism of regulation of TSH secretion in thyroid insufficiency.