The Effects of the Paleo Diet on Autoimmune Thyroid Disease: A Mixed Methods Review.

The aim of this systematic review was to examine the characteristics of Paleolithic diet (PD) interventions designed for adult patients with autoimmune thyroid disease (AITD) in order to determine if diet elements have the potential to successfully reduce thyroid antibodies (Ab) such as thyroglobulin (Tg), thyroid peroxidase (TPO), and thyroid stimulating hormone receptor (TSHR), and improve thyroid hormones (thyroxine (T4), triiodothyronine (T3) and thyroid stimulating hormone (TSH)) or resolve AITD pathogenesis. Randomized controlled trials (RCTs) with an adult population of 18 years and older, diagnosed with Hashimoto's thyroiditis (HT) or Graves' disease (GD) (Basedow's), who were placed on a diet of Paleolithic or ancestral nature, and achieved reduction of AITD Abs, improvement of thyroid hormones, and, or resolution of AITD were searched. Various electronic databases were used. Bias was assessed using critical appraisal tools from the Scottish Intercollegiate Guidelines Network (SIGN) and Joanna Briggs Institute (JBI). Studies were excluded according to exclusion criteria and results analyzed. One randomized controlled trial (RCT), a pilot study, and six case studies were found. In total, eight AITD studies focusing on Paleolithic or ancestral interventions were located. In highlight, females were the predominant gender. Case studies solely focused on AITD with protocols ranging from 8-60 weeks. All studies showed clinical improvements, one had significant improvement, two showed AITD resolution. After structured evaluation of nutritional interventions utilizing the PD on the effects of AITD, it was concluded foods of ancestral nature along with the addition of specific supplements, food components, exercise and mindfulness meditation, and exclusion of modern day foods have a considerable impact on thyroid Ab and hormones. The relevant studies suggest while this dietary protocol can be useful in clinical practice, larger-scale studies need to be conducted. Key teaching pointsThere are currently no dietary interventions recommended for the treatment of autoimmune thyroid disease. The Paleo diet has been documented to improve AITD antibodies and thyroid hormones in both Hashimoto's thyroiditis and Graves' disease.The Paleo diet can provide a natural source of nutrients similar to supplemental nutrients that have shown positive results on AITD.The paleo diet provides specific macronutrient percentages that may be beneficial in reducing AITD antibodies, while improving thyroid hormones.Methylation supplementation may be useful in AITD cases.

2015 Recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative

Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients' and clinicians' values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow-up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti-rheumatic drugs (DMARDs), as well as the roles of non-steroidal anti-rheumatic drugs and non-pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR.(AU)

Modification and validation of the Birmingham Vasculitis Activity Score (version 3).

BACKGROUND: Comprehensive multisystem clinical assessment using the Birmingham Vasculitis Activity score (BVAS) is widely used in therapeutic studies of systemic vasculitis. Extensive use suggested a need to revise the instrument. The previous version of BVAS has been revised, according to usage and reviewed by an expert committee. OBJECTIVE: To modify and validate version 3 of the BVAS in patients with systemic vasculitis. METHODS: The new version of BVAS was tested in a prospective cross-sectional study of patients with vasculitis. RESULTS: The number of items was reduced from 66 to 56. The subscores for new/worse disease and persistent disease were unified. In 313 patients with systemic vasculitis, BVAS(v.3) correlated with treatment decision (Spearman's r(s) = 0.66, 95% CI 0.59 to 0.72), BVAS1 of version 2 (r(s) = 0.94, 95% CI 0.92 to 0.96), BVAS2 of version 2 in patients with persistent disease (r(s) = 0.60, 95% CI 0.21 to 0.83), C-reactive protein levels (r(s) = 0.43, 95% CI 0.31 to 0.54), physician's global assessment (r(s) = 0.91, 95% CI 0.89 to 0.93) and vasculitis activity index (r(s) = 0.88, 95% CI 0.86 to 0.91). The intraclass correlation coefficients for reproducibility and repeatability were 0.96 (95% CI 0.95 to 0.97) and 0.96 (95% CI 0.92 to 0.97), respectively. In 39 patients assessed at diagnosis and again at 3 months, the BVAS(v.3) fell by 17 (95% CI 15 to 19) units (p<0.001, paired t test). CONCLUSION: BVAS(v.3) demonstrates convergence with BVAS(v.2), treatment decision, physician global assessment of disease activity, vasculitis activity index and C-reactive protein. It is repeatable, reproducible and sensitive to change. The new version of BVAS is validated for assessment of systemic vasculitis.

Correlation of angiographic morphology and clinical presentation in unstable angina.

OBJECTIVES: This study sought to correlate angiographically detected complex lesions and intracoronary thrombus with the severity of clinical presentation in unstable angina (UA). BACKGROUND: Unstable angina is usually related to acute thrombosis superimposed on a disrupted plaque. Complex and thrombotic lesions are more prevalent in UA and have been associated with a worse prognosis. The highest levels of the Braunwald classification of UA (III = rest angina within 48 h of presentation; C = postinfarction angina; and c = angina refractory to maximal medical therapy) can be used to assess the severity of clinical presentation, but they have not been directly correlated with thrombotic and complex lesions. METHODS: We conducted a prospective study of 284 patients with UA who underwent cardiac catheterization. A single angiographer with no knowledge of the clinical classifications interpreted all angiograms. Culprit lesions identified in 200 patients were classified as simple or complex. Complex lesions included the categories complex morphology, intracoronary thrombus (ICT) or total occlusion. Lesions were also quantitatively analyzed, and Thrombolysis in Myocardial Infarction (TIMI) flow was assessed. Univariate and multivariate logistic regression analyses of the angiographic findings were performed controlling for all cardiac risk factors, previous angioplasty or bypass surgery and multivessel disease, and we sequentially compared Braunwald classes III, C and c with classes < III, < C and < c, respectively. RESULTS: Class III was associated with complex lesions (p = 0.04) and decreased TIMI flow (p = 0.03). Class C angina correlated with complex lesions (p = 0.04), ICT (p = 0.005) and decreased TIMI flow (p = 0.03). Class c angina was associated with ICT (p = 0.02). The degree of stenosis by quantitative angiography was not associated with any particular Braunwald class. CONCLUSIONS: Recent rest pain and refractory or postinfarction UA, or both, are strongly associated with the general category of complex lesions and specifically with angiographically detected ICT and decreased TIMI flow.

Proton efflux from rat intestinal basal-lateral membrane vesicles is stimulated by ATP and Na+.

1. ATP-stimulated 22Na uptake and 14C-methylamine efflux were studied in inside-out rat intestinal basal-lateral membrane vesicles (BLMV). 2. Uptake of 22Na by basal-lateral membrane vesicles was stimulated by addition of ATP and by an acidic vesicle interior. 3. Efflux of 14C-methylamine was stimulated by ATP and Na+. 4. 14C-methylamine efflux was not influenced by vanadate or amiloride by themselves but was inhibited by the presence of both agents. 5. These data are consistent with a basal-lateral proton translocation mechanism which may be responsible for alkalinization of the lateral intercellular space and implicates the Na+-pump in this mechanism.

Weak base binding and transport in pig brush border membrane vesicles.

Uptake of the weak bases, benzylamine and amphetamine, were characterized with pig intestinal brush border membrane vesicles. The absence of osmotic sensitivity indicated weak base binding and little or no transport into the brush border membrane vesicles at pH 7.4. Benzylamine binding was increased 30-fold when medium pH was increased from 7.0 to 9.0, which indicated binding of the nonionized form of benzylamine. Uptake of benzylamine into an osmotically sensitive space was observed at pH 9.0 in the presence of NaCl and no osmotic sensitivity was observed in the presence of KCl. The apparent energy of activation of benzylamine binding was 8.4 kCal/mol which is higher than values normally associated with a simple physical process such as diffusion or partition into the membrane. Benzylamine binding was saturable and two binding sites (KD = 25 microM, KD = 2.5 mM) were discriminated. Inhibition experiments with structurally related compounds indicated a high degree of structural selectivity for the binding sites. Analysis of inhibition patterns indicated that the amine nitrogen may act as a hydrogen acceptor for hydrogen bond formation. These results indicate binding of nonionized primary amines to specific sites on intestinal brush border membranes. The binding of primary amines may be important as a step in translocation and/or membrane discrimination between ionized and nonionized weak bases.

Effect of Na+ on intestinal succinate transport and metabolism in vitro.

The effect of Na+ on 14CO2 production from [14C]succinate was studied in isolated rat enterocytes, and Na+-dependent succinate transport was characterized in pig intestinal brush-border membrane vesicles. The production of 14CO2 from [14C]succinate by enterocytes was decreased 12-fold when Na+ was replaced by N-methyl-D-glucamine in the absence of glutamine and 20-fold in the presence of 0.2 or 0.5 mM glutamine. The ratio of 14CO2 produced from [1,4-14C]succinate to that produced by [2,3-14C]succinate was not affected by Na+ replacement, indicating that the pattern of tricarboxylic acid cycle metabolism was not altered. The uptake of [14C]succinate by brush-border membrane vesicles was stimulated 10-fold in the presence of 100 mM NaCl compared with 100 mM KCl. When succinate uptake was corrected to transport into an osmotically sensitive space, the magnitude of the Na+ stimulation was 20-fold. Succinate transport into brush-border membrane vesicles was Na+ dependent, electroneutral, nonconcentrative, with an apparent Na+-succinate coupling ratio of 2:1. Results of this study indicate that Na+-stimulated CO2 production by enterocytes can be explained by the effect of Na+ on succinate transport across the brush-border membrane.