Patient consultation about a trial of therapeutic plasma exchange for complex regional pain syndrome.

BACKGROUND: Complex regional pain syndrome (CRPS) is a severe post-traumatic chronic pain condition affecting distal limbs, for which few effective treatments exist. Complex regional pain syndrome is listed in the 2016 American Society for Apheresis guidelines as an indication for plasma exchange treatment, but patient perspectives are lacking. STUDY DESIGN AND METHODS: We convened a "patient and public consultation exercise." Supervised by a clinical ethicist, the case for using therapeutic plasma exchange (TPE) was presented by a researcher and two TPE experts to five patients with severe, long-standing CRPS and to one relative. Discussions were recorded and transcribed. RESULTS: Participants supported the technology's use but expressed concern that the small trauma of repeat cannulations of CRPS unaffected limbs might theoretically cause a spread of the condition, a risk which requires highlighting when taking consent. For a preliminary trial, the participants proposed to include no less than 10, preferably 20 participants. They suggested that the threshold for a decision to conduct a definite trial based on preliminary trial results should be set no higher than 1/5 patients achieving >30% pain reduction in the preliminary trial, with half of these responders achieving >50%. The use of sham-TPE and a long trial duration (1 year) of a definite, parallel trial was considered acceptable, provided patients would be offered voluntary swap to the other trial arm at the end of the main trial period. CONCLUSION: These results provide pertinent patient views about TPE treatment which can inform both clinical consultation and consent procedure and the design of future trials.

Temporary sympathectomy in chronic refractory angina: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Temporary sympathectomy by injection of bupivacaine at the site of the left stellate ganglion is used in the management of refractory angina at several UK centres. Although patients frequently report significant reduction in symptoms, efficacy has not been established by double-blind, randomised placebo-controlled trial (RCT). OBJECTIVE: To investigate the efficacy of the procedure for the first time by a double-blind RCT. METHODS: Consecutive patients referred to the authors' National Health Service (NHS) angina centre who were candidates for temporary sympathectomy were invited to participate in a trial. A total of 65 patients were randomised to receive either bupivacaine or saline injections. Identical syringes were prepared remotely, blinding patients and staff from randomisation. Cardiac autonomic function was measured 3 hours pre- and post-injection using new heart rate variability (HRV) analyses. Angina episodes were recorded contemporaneously by patients in study diaries in the 7-day periods pre- and post-injection. RESULTS: In 51 patients suitable for analysis, no significant differences between the active and placebo groups were found in patient-recorded frequency or intensity of angina episodes pre- and post-injection. However, across both groups combined, a significant difference was found in the frequency of angina episodes pre- and post-injection. CONCLUSION: The reduction in frequency of angina episodes produced by this procedure may not be due to drug pharmacology. It may be a placebo response or due to the mechanical effects of the injection of fluid. There is a need for further work using a larger patient cohort considering both mechanical and psychological factors.

Iodine treatment in children with subclinical hypothyroidism due to chronic iodine deficiency decreases thyrotropin and C-peptide concentrations and improves the lipid profile.

BACKGROUND: Chronic iodine deficiency (ID) increases thyrotropin (TSH) concentrations and produces a thyroid hormone pattern consistent with subclinical hypothyroidism (ScH). ScH may be associated with cardiovascular disease risk factors. Thus, the study aim was to determine if iodine treatment of children with elevated TSH concentrations due to ID would affect their lipid profile, insulin (C-peptide) levels, and/or subclinical inflammation. METHODS: In controlled intervention trials of oral iodized oil or iodized salt, 5-14-year-old children from Morocco, Albania, and South Africa with TSH concentrations > or = 2.5 mU/L (n = 262) received 400 mg iodine as oral iodized oil or household distribution of iodized salt containing 25 microg iodine/g salt. At baseline and after 5 or 6 months, urinary iodine (UI) and blood concentrations of total thyroxine, TSH, C-reactive protein (CRP), C-peptide, and lipids were measured. RESULTS: Median (range) UI at baseline was 46 (2-601) microg/L. Compared to the control group, iodine treatment significantly increased UI and total thyroxine and decreased TSH, C-peptide, and total and low-density lipoprotein cholesterol. The mean low-density lipoprotein/high-density lipoprotein cholesterol ratio fell from 3.3 to 2.4 after iodine treatment (p < 0.001). Iodine treatment had no significant effect on concentrations of high-density lipoprotein cholesterol, triglycerides, or C-reactive protein. CONCLUSIONS: Correction of ID-associated ScH improves the insulin and lipid profile and may thereby reduce risk for cardiovascular disease. This previously unrecognized benefit of iodine prophylaxis may be important because ID remains common in rapidly developing countries with increasing rates of obesity and cardiovascular disease.

A brief cognitive-behavioral intervention reduces hospital admissions in refractory angina patients.

Chronic refractory angina is an increasingly prevalent, complex chronic pain condition, which results in frequent hospitalization for chest pain. We have previously shown that a novel outpatient cognitive-behavioral chronic disease management program (CB-CDMP) improves angina status and quality of life in such patients. In the present study of 271 chronic refractory angina patients enrolled in our CB-CDMP, total hospital admissions were reduced from 2.40 admissions per patient per year to 1.78 admissions per patient per year (P<0.001). The rising trend of total hospital bed day occupancy prior to enrollment fell from 15.48 days per patient per year to a stable 10.34 days per patient per year (P<0.001). There were 32 recorded myocardial infarctions prior to enrollment compared to eight in the year following enrollment (14% vs. 2.3%, P<0.001) and overall mortality was lower that comparable groups treated with surgery. This study shows that educating patients and demystifying angina using a brief outpatient CB-CDMP produces an immediate and sustained reduction in hospital admission costs that represents a major potential health care saving. This benefit accrues in addition to the known effects of CB-CDMP on symptoms and quality of life. These data suggest that a CB-CDMP approach to symptom palliation represents a low cost alternative to palliative revascularization.

A new platinum complex of triazine demonstrates G1 arrest with novel biological profile in human breast cancer cell line, MDA-MB-468.

A novel class of platinum(II) complexes of pyridine sulfide derivatives of triazine was synthesized, characterized, and investigated using the human breast cancer cell line, MDA-MB-468. S-30 was one of the most potent derivatives of its class (IC(50), 0.39 microM) eliciting the greatest biological response. S-30 induced arrest in the G1 phase and apoptosis (TUNEL assay) in a p53/p21(WAF1/CIP1)-consistent manner. Modeling and docking experiments were performed for three known targets for cisplatin, d(GpG), d(ApG), and a protein (Cu/Zn superoxide dismutase, SOD) from bovine origin. A Blast search of bovine SOD was performed to identify analogous human protein targets resulting in about 22 human proteins. A multi-sequence alignment of those targets showed >80% sequence identity and >88% similarity. One of them is SOD1 that is differentially expressed (based on global gene expression pattern) in various forms of cancer and other diseases. SOD1 controls apoptosis via p53/BAD/BAX/BCL2 in the amyotrophic lateral sclerosis (ALS) pathway and is also involved in various other KEGG's pathways. Results suggest that the S-30 is a potential cytotoxic agent.

Treatment of iodine deficiency in school-age children increases insulin-like growth factor (IGF)-I and IGF binding protein-3 concentrations and improves somatic growth.

CONTEXT: Iodine deficiency in utero impairs fetal growth, but the relationship between iodine deficiency and postnatal growth is less clear. OBJECTIVE: The objective of the study was to determine whether iodine repletion improves somatic growth in iodine-deficient children and investigate the role of IGF-I and IGF binding protein (IGFBP)-3 in this effect. DESIGN, PARTICIPANTS, AND INTERVENTIONS: Three prospective, double-blind intervention studies were done: 1) in a 10-month study, severely iodine-deficient, 7- to 10-yr-old Moroccan children (n = 71) were provided iodized salt and compared with children not using iodized salt; 2) in a 6-month study, moderately iodine-deficient, 10- to 12-yr-old Albanian children (n = 310) were given 400 mg iodine as oral iodized oil or placebo; 3) in a 6-month study, mildly iodine-deficient 5- to 14-yr-old South African children (n = 188) were given two doses of 200 mg iodine as oral iodized oil or placebo. At baseline and follow-up, height, weight, urinary iodine (UI), total T4 (TT4), TSH, and IGF-I were measured; in Albania and South Africa, IGFBP-3 was also measured. RESULTS: In all three studies, iodine treatment increased median UI to more than 100 microg/liter, whereas median UI in the controls remained unchanged. In South Africa, iodine repletion modestly increased IGF-I but did not have a significant effect on IGFBP-3, TT4, or growth. In Albania and Morocco, iodine repletion significantly increased TT4, IGF-I, IGFBP-3, weight-for-age z scores, and height-for-age z scores. CONCLUSION: This is the first controlled study to clearly demonstrate that iodine repletion in school-age children increases IGF-I and IGFBP-3 concentrations and improves somatic growth.

Iodine supplementation improves cognition in iodine-deficient schoolchildren in Albania: a randomized, controlled, double-blind study.

BACKGROUND: Iodine is required for the production of thyroid hormones, which are necessary for normal brain development and cognition. Although several randomized trials examined the effect of iodine supplementation on cognitive performance in schoolchildren, the results were equivocal. OBJECTIVE: We aimed to ascertain whether providing iodized oil to iodine-deficient children would affect their cognitive and motor performance. DESIGN: In a double-blind intervention trial, 10-12-y-old children (n = 310) in primary schools in rural southeastern Albania were randomly assigned to receive 400 mg I (as oral iodized oil) or placebo. We measured urinary iodine (UI), thyroid-stimulating hormone (TSH), and total thyroxine (TT4) concentrations and thyroid gland volume (by ultrasound). The children were given a battery of 7 cognitive and motor tests, which included measures of information processing, working memory, visual problem solving, visual search, and fine motor skills. Thyroid ultrasound and the biochemical and psychological tests were repeated after 24 wk. RESULTS: At baseline, the children's median UI concentration was 43 microg/L; 87% were goitrous, and nearly one-third had low concentrations of circulating TT4. Treatment with iodine markedly improved iodine and thyroid status: at 24 wk, median UI in the treated group was 172 microg/L, mean TT4 was approximately 40% higher, and the prevalence of hypothyroxinemia was < 1%. In the placebo group after the intervention, these variables did not differ significantly from baseline. Compared with placebo, iodine treatment significantly improved performance on 4 of 7 tests: rapid target marking, symbol search, rapid object naming, and Raven's Coloured Progressive Matrices (P < 0.0001). CONCLUSION: Information processing, fine motor skills, and visual problem solving are improved by iodine repletion in moderately iodine-deficient schoolchildren.

Severe iodine deficiency in southern Albania.

Albania does not yet have a national program for control of iodine deficiency and there are no recent data on the severity of the iodine deficiency disorders (IDD) in the country. The aim of the present study was to assess current IDD status in southern Albania. In primary school children in urban and rural areas urinary iodine concentration (UI) and iodine concentration in salt at retail and household levels was measured. Goiter was graded by palpation and thyroid volume determined by ultrasound. Children aged 5-14 yr (n = 826) were sampled at 2 urban and 5 rural primary schools. In the 2 urban schools, the median UI was 45 micrograms/L, the goiter prevalence was 32%, and salt iodine levels were inadequate (< 15 micrograms/g) in 78% of household salt samples. In the rural schools, the median UI was 17 micrograms/L, the goiter prevalence was 95%, and no household salt samples were adequately iodized. Among children in the rural schools, 73% had grade 2 goiter and 20% had nodular changes detected by thyroid ultrasound. In southern Albania, school children in urban areas are moderately iodine deficient and those in rural villages are severely iodine deficient. These findings suggest that regional distribution of oral iodized oil capsules is indicated to control IDD in vulnerable groups until salt iodization is implemented.

Low-dose methadone has an analgesic effect in neuropathic pain: a double-blind randomized controlled crossover trial.

The analgesic effectiveness and adverse effect incidence of a daily dose of 10 or 20 mg of oral methadone were evaluated in 18 patients with a diverse range of chronic neuropathic pain syndromes, who had all responded poorly to traditional analgesic regimens. Analgesia was seen after each dose of methadone. As compared with placebo, the 20 mg daily dose (given as 10 mg bd) resulted in statistically significant (P = 0.013-0.020) improvements in patient Visual Analogue Scale ratings of maximum pain intensity, average pain intensity and pain relief, recorded at the same time daily. The analgesic effects extended over 48 hours, as shown by statistically significant (P = 0.013-0.020) improvements in all three outcomes on the rest days instituted between each daily dose. Analgesic effects (lowered maximum pain intensity and increased pain relief, on the day of dosing only) were also seen when the lower daily dose of 10 mg methadone (given as 5 mg bd) was used, but these failed to reach statistical significance (P = 0.064 and 0.065, respectively). Interpatient analysis showed that the analgesic effects were not restricted to any particular type of neuropathic pain. Patient compliance was high throughout the trial. One patient withdrew during the 10 mg and six during the 20 mg methadone treatment periods. This is the first double-blind randomized controlled trial to demonstrate that methadone has an analgesic effect in neuropathic pain.

Nonplanar aromatic compounds. 8. Synthesis, crystal structures, and aromaticity investigations of the 1,n-dioxa[n](2,7)pyrenophanes. How does bending affect the cyclic pi-electron delocalization of the pyrene system?

A series of 1,n-dioxa[n](2,7)pyrenophanes (n = 7-12) with increasingly nonplanar pyrene moieties was synthesized by a 9-10 step sequence starting from 5-hydroxyisophthalic acid. The crystal structure of each member of this series was determined crystallographically. Several spectroscopic properties were found to vary with the extent of the nonplanarity of the pyrene unit. The way in which the distortion from planarity of the pyrene system influences its pi-electron delocalization was investigated by using two quantitative descriptors of aromaticity based on geometry (HOMA) and magnetism (magnetic susceptibility and NICS). Both methods suggest that the aromaticity of the pyrene moiety is diminished only slightly upon increasing the bend angle theta from 0 degrees to 109.2 degrees.

Metal Complexes of 1-Oxa-4,7-dithiacyclononane.

The ligand 1-oxa-4,7-dithiacyclononane (L) and its complexes [Pd(L)Cl(2)], [Cu(L)(2)][ClO(4)].CH(3)CN, [Cu(L)Br](2), and [Co(L)(2)][ClO(4)](2).2CH(3)NO(2) have been prepared. Crystal data are as follows. For monoclinic [Pd(L)Cl(2)], C(6)H(12)Cl(2)OPdS(2): space group P2(1)/n; a = 8.464(2), b = 12.199(2), c = 10.384(2) Å; beta = 105.09(1) degrees; Z = 4; R = 0.024, R(w) = 0.033 for 1721 reflections. For monoclinic [Cu(L)(2)][ClO(4)].CH(3)CN, C(14)H(27)ClCuNO(6)S(4): space group P2(1)/n; a = 7.743(2), b = 19.515(5), c = 15.017(2) Å; beta = 102.85(2) degrees; Z = 4; R = 0.036, R(w) = 0.038 for 3124 reflections. For triclinic [Cu(L)Br](2), (C(6)H(12)BrCuOS(2))(2): space group P&onemacr;; a = 7.809(5), b = 8.880(3), c = 7.567(2) Å; alpha = 92.44(3), beta = 102.85(2), gamma = 99.30(4) degrees; Z = 2; R = 0.027, R(w) = 0.027 for 1494 reflections. For monoclinic [Co(L)(2)][ClO(4)](2).2CH(3)NO(2), C(14)H(30)Cl(2)CoN(2)O(14)S(4): space group P2(1)/c; a = 10.333(3), b = 14.293(6), c = 9.365(4) Å; beta = 100.89(3) degrees; Z = 2; R = 0.067, R(w) = 0.058 for 1517 reflections. The ligand displays a variety of conformations in these structures. The palladium complex does not undergo 1,4-heteroatom binding site fluxional processes but does dissociate in dimethyl sulfoxide. An apical Pd.O (2.968(3) Å) interaction has been detected by both NMR and X-ray studies. The Cu(I) cation is tetrahedral with a [2+2] mode of ligand coordination. [Cu(L)Br](2) involves two Br bridges between coppers and two thioether sulfurs from a ligand to complete each copper's tetrahedral coordination sphere. Surprisingly, the cyclic voltammetric behavior of the copper complexes is similar to that of 1,4,7-trithiacyclononane complexes. The cation [Co(L)(2)](2+) is pseudooctahedral with nearly regular angles at cobalt but a long (2.235(6) Å) Co-O bond due to Jahn-Teller distortion. The complex [Co(L)(2)][ClO(4)](2) is magnetically dilute and low-spin over the temperature range 5-292 K.