Recombinant human TSH increases the efficacy of a fixed activity of radioiodine for treatment of multinodular goitre

Context: High doses of ¹³¹I are usually needed in the treatment of multinodular goitre (MNG) for effective thyroid volume (TV) reduction. Recombinant human thyroid‐stimulating hormone (rhTSH) is an adjuvant to enhance ¹³¹I uptake, allowing a decrease in radiation activity and enhancing ¹³¹I efficacy. Objective: To evaluate whether rhTSH increases the efficacy of a fixed activity of ¹³¹I for the treatment of MNG. Design:  Two‐year, observational, placebo‐controlled study. Setting: Patients received 0.1 mg rhTSH (A), 0.005 mg rhTSH (B) or placebo (C). A fixed activity of 1.11 GBq of ¹³¹I was administered 24 h after rhTSH or placebo. Patients:  A total of 28 outpatients (26 females and two males) with MNG. Measurements: TSH, free T4, T3, thyroglobulin (Tg) and TV. Results: Basal radioactive iodine uptake and TV values were comparable among all groups. After rhTSH or placebo, peak levels of TSH, free T4, T3 and Tg were higher in A than in B or in C (p < 0.05). Hyperthyroidism was observed in A (n = 2), B (n = 6) and C (n = 4). Thyroid enlargement was reported in A (n = 3) and B (n = 6). After 24 months, 10 patients developed hypothyroidism (four in A, three in B and three in C). TV reduction was similar between A and B (37.2 ± 25.5% vs. 39.3 ± 27.9%, p = 0.88), but different from the non‐significant reduction in C (15.3 ± 28.3%, p = 0.08). Conclusions: Followed by 1.11 GBq, a very low dose of 0.005 mg rhTSH was equally safe and effective as 0.1 mg rhTSH. Both doses increased the efficacy of radioiodine. Adverse events were mild, transient and readily treatable.     

Genetic and environmental factors in the aetiology of simple goiter

The aetiology of simple goitre, affecting up to 5% of a population in iodine-sufficient areas and over 10% in endemic areas, is incompletely understood. It is generally believed that the development of simple goitre, whether endemic or sporadic, depends on complex interactions between genetic, environmental and endogenous factors. The importance of genetic factors is evident from the clustering of simple goitre within families and from a higher concordance rate for goitre in monozygotic than in dizygotic twins. Recently, studies assessing the role of specific candidate genes or genetic markers in the aetiology of simple goitre have given conflicting data in various families. However, there may well be single genes playing a major role within certain families, eg the thyroglobulin (Tg) gene, the thyroid-stimulating hormone receptor (TSHR) gene, the Na⁺/I^- symporter (NIS) gene, and the multinodular goitre marker 1 (MNG1) on chromosome 14, but the genes will vary from family to family. In addition, family and twin studies also indicate a modest to major role for environmental factors in the aetiology of simple goitre. Clearly, iodine deficiency and cigarette smoking are the most important environmental risk factors associated with the genesis of simple goitre. Other suggested risk factors include naturally occurring goitrogens, emotional stress and certain drugs and infections. Ongoing studies focus on whole-genome screening in multiplex families as well as on large population-based case-control studies. However, the possibility that simple goitre is a heterogeneous disease without a single well-defined genotype and phenotype should be left open.     

Genetic and environmental factors in the aetiology of simple goitre

The aetiology of simple goitre, affecting up to 5% of a population in iodine-sufficient areas and over 10% in endemic areas, is incompletely understood. It is generally believed that the development of simple goitre, whether endemic or sporadic, depends on complex interactions between genetic, environmental and endogenous factors. The importance of genetic factors is evident from the clustering of simple goitre within families and from a higher concordance rate for goitre in monozygotic than in dizygotic twins. Recently, studies assessing the role of specific candidate genes or genetic markers in the aetiology of simple goitre have given conflicting data in various families. However, there may well be single genes playing a major role within certain families, eg the thyroglobulin (Tg) gene, the thyroid-stimulating hormone receptor (TSHR) gene, the Na+/I- symporter (NIS) gene, and the multinodular goitre marker 1 (MNG1) on chromosome 14, but the genes will vary from family to family. In addition, family and twin studies also indicate a modest to major role for environmental factors in the aetiology of simple goitre. Clearly, iodine deficiency and cigarette smoking are the most important environmental risk factors associated with the genesis of simple goitre. Other suggested risk factors include naturally occurring goitrogens, emotional stress and certain drugs and infections. Ongoing studies focus on whole-genome screening in multiplex families as well as on large population-based case-control studies. However, the possibility that simple goitre is a heterogeneous disease without a single well-defined genotype and phenotype should be left open.     

阿那曲唑联合依维莫司治疗乳腺癌的效果及对血清HER-2/neu、p185水平的影响

目的探究阿那曲唑联合依维莫司用于治疗乳腺癌的临床疗效及其对患者血清中人类表皮生长因子受体2蛋白(HER-2/neu)、p185水平的影响。方法选取2013年1月至2018年12月广元市第一人民医院治疗的符合纳入标准的患者1000例,按照随机数字表法分为对照组(n=500)和观察组(n=500)。对照组给予口服阿那曲唑片,观察组在对照组的基础上给予口服依维莫司片。治疗3个月后,观察比较2组患者的临床疗效及不良反应发生率,比较2组患者雌激素、HER-2/neu、p185水平。结果观察组的临床缓解率为60.60%,要明显高于对照组(54.20%),差异有统计学意义(χ^2=4.190,P=0.041)。治疗前,2组患者的雌二醇(E2)、黄体生成素(LH)、HER-2/neu、p185水平比较,差异无统计学意义(P>0.05)。经过3个月的治疗,观察组的E2、LH、HER-2/neu、p185水平均明显低于对照组(t=8.148,P=0.000;t=85.170,P=0.000;t=20.209,P=0.000;t=16.109,P=0.000)。治疗过程中,对照组和观察组患者不良反应发生率分别为8.60%和7.60%,差异无统计学意义(χ^2=0.340,P=0.562)。结论阿那曲唑联合依维莫司治疗乳腺癌具有良好的临床疗效,可抑制肿瘤细胞的生长发育,降低患者体内雌激素水平,且安全性高。     

S-fluoxetine in the prophylaxis of migraine: a phase II double-blind randomized placebo-controlled study

S-fluoxetine is the long-acting enantiomer of the racemic antidepressant serotonin reuptake inhibitor. Sixty-five patients needing migraine prophylaxis were recruited into a phase II, double-blind, placeho-controlled trial. After a 1-month placebo run-in, 53 patients met entry criteria with regard to attack frequency and were randomized, 27 to S-fluoxetine and 26 to matching placebo. Three failed to start treatment and there were 17 early discontinuations, 9 from S-fluoxetine, 8 from placebo, at similar times and for similar reasons. The primary efficacy variable was attack frequency and analysis compared decline-from-baseline in the two groups. This was earlier and greater (1.7 attacks/28 days, or 52%) on active therapy than on placebo (1.1 attacks/28 days, or 27%), and statistically significant in month 2 (F=4.93; p =0.033) and month 4 (F=4.55; p =0.04l). As secondary measures of efficacy, migraine-days per month and Patient's Global Impression of Disease Severity coherently reflected the changes in attack frequency. Mean attack severity and acute medication use (doses per attack) were unaltered by either treatment. There were no serious adverse events. Withdrawals for adverse events were four from each group but none was considered causally related. The finding of greater efficacy of S-fluoxetine than of placebo should he interpreted conservatively, since the analysis in the final month was made on only half of the entered patients. It supports progression to phase III evaluation, which was the purpose of the study.     

Oestriol in the Prophylactic Treatment of Recurrent Urinary Tract Infections in Postmenopausal Women

A block randomized, double-blind, group-comparative, placebo-controlled study was conducted to assess the effect of oestriol on recurrent urinary tract infections in postmenopausal women. 40 women, median age 78 years (66–91), 20 in each group, were treated with oestriol three mg p.o. per day or corresponding placebo for four weeks, followed by one mg per day for eight weeks. The main response parameter was the number of urinary tract infections per week in the two treatment periods. Both oestriol and placebo reduced the number of infections per week significantly in both periods, compared with the pretreatment period. There was no difference between oestriol and placebo treatment in the first period. In the second period, however, oestriol treatment was significantly more effective than placebo (p = 0.05). Correspondingly, there was a significant difference between the two groups in the vaginal pH at the end of the study (p > 0.05). We conclude that oestriol reduces recurrent urinary tract infections in postmenopausal women.     

Oestriol in the prophylactic treatment of recurrent urinary tract infections in postmenopausal women.

A block randomized, double-blind, group-comparative, placebo-controlled study was conducted to assess the effect of oestriol on recurrent urinary tract infections in postmenopausal women. 40 women, median age 78 years (66-91), 20 in each group, were treated with oestriol three mg p.o. per day or corresponding placebo for four weeks, followed by one mg per day for eight weeks. The main response parameter was the number of urinary tract infections per week in the two treatment periods. Both oestriol and placebo reduced the number of infections per week significantly in both periods, compared with the pretreatment period. There was no difference between oestriol and placebo treatment in the first period. In the second period, however, oestriol treatment was significantly more effective than placebo (p = 0.05). Correspondingly, there was a significant difference between the two groups in the vaginal pH at the end of the study (p less than 0.05). We conclude that oestriol reduces recurrent urinary tract infections in postmenopausal women.     

Randomised, placebo-controlled, double-blind study to investigate the efficacy and safety of the acute use of sodium picosulphate in patients with chronic constipation

There are few studies supporting the effective and safe use of laxatives for constipation. This study examined the short-term efficacy and safety of sodium picosulphate in patients with chronic constipation. Patients with a history of chronic constipation for at least 3 months were randomised to receive 7 mg sodium picosulphate or placebo for three consecutive nights. Patients recorded stool frequency and consistency, straining, bloating, and pain at baseline and during treatment. Vital signs, haematocrit, serum creatinine and electrolytes were monitored. Primary end-point for efficacy was the occurrence of a response to treatment, defined as improvement in stool frequency and occurrence of straining. All 57 randomised patients (sodium picosulphate n = 29, placebo n = 28; mean age 54.8 and 54.1 years) completed the study. Sodium picosulphate produced a treatment response (improved stool frequency and straining) in 82.8% compared with 50% in the placebo group (p = 0.010) and reduced bloating more often than placebo. There were no serious adverse events and one patient with diarrhoea and another with abdominal pain in each treatment group. There were no cardiovascular effects, changes in serum haematocrit, creatinine or electrolytes in either group. This study confirmed that sodium picosulphate is an effective, well-tolerated and safe laxative in the acute treatment of constipation.     

Polyphenolic natural products and natural product–inspired steroidal mimics as aromatase inhibitors

The discovery of biologically active polyphenolic natural products, including chalcones, stilbenes, flavanones, and isoflavones as steroidal mimics has proven to be a subject of considerable importance in medicine. Some of these natural compounds have been shown to modulate key human metabolic processes via steroidal hormone receptors, or to inhibit crucial enzymes involved in the biosynthesis of steroidal hormones themselves. Isoflavone polyphenolics such as genistein are well known for this “phytoestrogenic” biological activity. This review focuses on the ability of select polyphenolics and their synthetic derivatives to function as steroidal mimics in the inhibition of the enzyme aromatase, thereby lowering production of endogenous estrogen growth hormones. The discovery of potent, natural product–based aromatase inhibitors (AIs) as hit compounds has led to the introduction of steroidal-based irreversible inhibitors, such as exemestane and reversible AIs such as anastrozole and letrozole, now standard therapy in the treatment of estrogen receptor–positive breast cancer and other hormone related indications. Pursuit of this strategy over the last few decades has been largely successful although complications and challenges remain. This review highlights the aromatase activity of natural stilbenes, chalcones, and flavanones and synthetically inspired versions thereof and draws attention to new and under-investigated areas within each class worthy of pursuit.     

CAN PROPHYLACTIC ORAL ERYTHROMYCIN REDUCE TIME TO FULL ENTERAL FEEDS IN PRETERM NEONATES?

Efficacy of oral, prophylactic erythromycin in reducing the time to establish full enteral feeds (150 ml/kg/day) was assessed in neonates < 32 weeks, ready for enteral feeds. Seventy-three consecutive neonates were randomised to receive oral erythromycin ethyl succinate (n = 36) or placebo (n = 37) in a double-blind trial until full enteral feeds or 14 days of therapy were reached. A prospectively designed feeding regimen, including plan of action for signs of feed intolerance, was common for all enrolled neonates. The median gestational age, birth weight and postnatal age at start of feeds were 29 versus 30 weeks (p = 0.40), 1232 versus 1280 g (p = 0.96) and 5 versus 5 days (p = 0.84) for erythromycin and placebo group, respectively. Time to achieve full feeds was not significantly different in the two groups. (median times: erythromycin 93.5 versus placebo 104 hours, p = 0.60). Erythromycin-related side-effects did not occur.     

Initialization of adjuvant hormonal treatment for breast cancer

The introduction of aromatase inhibitors (AI) has resulted in practice change approaches in the treatment of early breast cancer. In this paper, we analyze the most relevant studies including the ATAC, BIG 1-98, TEAM, MA-17, NSABP B-33, and ABSCG-6 studies. Postmenopausal patients with hormone receptor-positive early breast cancer should be treated with AI for 5 years. For patients who have been initiated with tamoxifen (TAM), switching to an AI to complete 5 years of treatment is also recommended. The results of the extended adjuvant therapy studies recommend the use of an AI (anastrozole, letrozole, or exemestane) after the completion of standard TAM treatment. With regards to premenopausal women, TAM is the recommended adjuvant hormonal treatment for pre- and perimenopausal women. There is no indication for the use of AI in these subgroups of patients. Finally, determination of CYP 2D6 polymorphisms could be considered when choosing the best adjuvant hormonal treatment option.     

Low level laser versus placebo in the treatment of tennis elbow.

The effect of low level laser (GaAs) on lateral epicondylitis was investigated in a double-blind, randomized, controlled study. Thirty patients were assigned equally to a laser (n = 15) or a placebo laser (n = 15) group. All patients received eight treatments and were evaluated subjectively and objectively before, at the end of, and four weeks after treatment. Patients also completed a follow-up questionnaire on an average of five to six months after treatment. A significant improvement in the laser compared to the placebo group was found on visual analog scale (p = 0.02) and grip strength (p = 0.03) tests four weeks after treatment. In this study low level laser therapy was shown to have an effect over placebo; however, as a sole treatment for lateral epicondylitis it is of limited value. Further studies are needed to evaluate the reliability of our findings and to compare laser to other established treatment methods.     

Risk reduction and tolerability of fluvastatin in patients with the metabolic syndrome: a pooled analysis of thirty clinical trials

OBJECTIVE: This pooled analysis of 30 completed clinical trials assessed the efficacy and safety profile in reducing cardiovascular disease (CVD) risk of fluvastatin in the treatment of dyslipidemia in patients with and without the metabolic syndrome (metS). METHODS: Data from 30 double-blind, randomized, placebo-controlled or fluvastatin-controlled trials with > or =6 weeks of active treatment and daily fluvastatin doses of 20, 40, and 80 mg were pooled. Patients received fluvastatin or placebo. Linear contrasts from an analysis of covariance model containing factors for trial and treatment group (immediate-release fluvastatin 20, 40, 80 mg; extended-release fluvastatin 80 rag; or placebo), and using the baseline value as covariate, were used to compare the percentage changes from baseline to the first postbaseline assessment of all lipid parameters. A Cox regression analysis compared the all-fluvastatin group to the placebo group with regard to the time to occurrence of clinical end points from 5 pooled studies, each with a mean treatment duration >1 year wherein clinical end points were reviewed by an adjudication committee. These analyses were performed separately for patients with and without metS. RESULTS: This pooled analysis included data from 7043 patients (4095 men, 2948 women; all-fluvastatin group with and without metS, 2529 and 2052 patients, respectively; placebo group with and without metS, 1514 and 948 patients, respectively). Patients with metS in the pooled fluvastatin group had a greater mean reduction in triglyceride levels (24.1% vs 6.7%), a greater mean increase in high-density lipoprotein cholesterol levels (10.3% vs -0.6%), and a similar mean reduction in low-density lipoprotein cholesterol levels (26.8% vs 26.7%) compared with the subgroup of patients without metS. Treatment with fluvastatin was associated with a significantly lower incidence of major adverse cardiovascular events (MACEs) (16.4% vs 22.0%) and an increase in the time to first MACE in patients with metS compared with placebo (hazard ratio = 0.728; P = 0.001). The incidences of adverse events, particularly those of concern (ie, myalgia and/ or increased blood creatine phosphokinase, alanine aminotransferase, and/or aspartate aminotransferase) with lipid-lowering therapy, were statistically similar between the patients who received fluvastatin and those who received placebo in the 2 subgroups. CONCLUSION: The results from this pooled analysis found that fluvastatin was effective in reducing CVD risk in the treatment of dyslipidemia in these patients with metS.     

The effect of different treatment modalities on oxidative stress in COPD

INTRODUCTION: Oxidant/antioxidant interactions are known to be important processes in the pathogenesis of chronic obstructive pulmonary disease (COPD). We aimed to evaluate the effects of corticosteroids (CS), and Nacetylcysteine (NAC) on plasma oxidant/antioxidant levels in patients with COPD. METHODS: This study utilised a single-blind, randomised, placebo-controlled, parallel-group methodology. We enrolled 58 patients with stable COPD and 30 healthy controls with similar demographic profiles. The patients with COPD were randomly divided into three treatment groups. Group 1 received basal treatment (regular ipratropium bromide and beta-2 agonist as needed), placebo CS and placebo NAC. In addition to basal treatment, group 2 received oral CS (methylprednisolone 40 mg/day) and placebo NAC. Group 3 received basal treatment plus NAC (600 mg/day) and placebo CS. Each group received treatment for 15 days. We measured plasma malondialdehyde (MDA) and superoxide dismutase (SOD) at the start and the end of study. RESULTS: Post-treatment plasma MDA levels were significantly lowered only in group 2 (P=0.004). No significant differences were found with respect to erythrocyte SOD levels. CONCLUSION: This study demonstrates that oral CS, by aiding the oxidant/antioxidant system, may offer a new therapeutic option in COPD treatment.     

Advances in endocrine therapy for breast cancer: considering efficacy, safety, and quality of life

Breast cancer is the most common cancer found in women in the United States. Endocrine therapy is the standard of care for most women with hormone receptor-positive tumors in adjuvant and metastatic settings. The selective estrogen response modifier tamoxifen has been the standard treatment for postmenopausal patients for many years. Numerous new endocrine therapy agents provide women with novel treatment options, including the nonsteroidal aromatase inhibitors anastrozole and letrozole, the steroidal aromatase inhibitor exemestane, and the estrogen receptor antagonist fulvestrant. Clinical trials have begun to define the role of these agents and their unique side-effect profiles. Nurses are vital in supporting patients in the decision-making process, managing side effects of treatment, and making observations to enhance understanding of the patient experience with new treatments. This article will assist nurses in educating patients about endocrine therapy options and their associated potential short- and long-term side effects, as well as treatment demands.     

Therapy of duodenal and prepyloric ulcers with cimetidine (author's transl)]

In a double-blind randomized trial 91 patients with endoscopically confirmed duodenal and/or prepyloric ulcers received either 1000 mg cimetidine daily (44 patients) or placebo (47 patients) for 4 weeks. At 2 weeks complete ulcer healing was significantly increased in patients receiving cimetidine (45%) in comparison with those treated with placebo (15%) (p less than 0.01). At 4 weeks 73% of the patients on cimetidine and 32% of those on placebo showed complete healing (p less than 0.001). Ulcer size decreased more rapidly with cimetidine than placebo (p less than 0.05). With respect to the number of pain-free days and nights cimetidine was significantly superior to placebo during the days of the second week only (p less than 0.05). Cimetidine patients consumed significantly less antacids than those receiving placebo (p less than 0.01). There was no significant correlations between ulcer healing and freedom from pain at the end of either cimetidine or placebo treatment in this study. No specific side effects referable to cimetidine were observed.     

An experimental study on the effectiveness of massage with aromatic ginger and orange essential oil for moderate-to-severe knee pain among the elderly in Hong Kong

OBJECTIVES: To assess the efficacy of an aromatic essential oil (1% Zingiber officinale and 0.5% Citrus sinesis) massage among the elderly with moderate-to-severe knee pain. METHOD: Fifty-nine older persons were enrolled in a double-blind, placebo-controlled experimental study group from the Community Centre for Senior Citizens, Hong Kong. The intervention was six massage sessions with ginger and orange oil over a 3-week period. The placebo control group received the same massage intervention with olive oil only and the control group received no massage. Assessment was done at baseline, post 1-week and post 4 weeks after treatment. Changes from baseline to the end of treatment were assessed on knee pain intensity, stiffness level and physical functioning (by Western Ontario and McMaster Universities Osteoarthritis index) and quality of life (by SF-36). RESULTS: There were significant mean changes between the three time-points within the intervention group on three of the outcome measures: knee pain intensity (p=0.02); stiffness level (p=0.03); and enhancing physical function (p=0.04) but these were not apparent with the between-groups comparison (p=0.48, 0.14 and 0.45 respectively) 4 weeks after the massage. The improvement of physical function and pain were superior in the intervention group compared with both the placebo and the control group at post 1-week time (both p=0.03) but not sustained at post 4 weeks (p=0.45 and 0.29). The changes in quality of life were not statistically significant for all three groups. CONCLUSION: The aroma-massage therapy seems to have potential as an alternative method for short-term knee pain relief.     

Selenium in Intensive Care (SIC): results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock

OBJECTIVE: Sepsis is associated with an increase in reactive oxygen species and low endogenous antioxidative capacity. We postulated that high-dose supplementation of sodium-selenite would improve the outcome of patients with severe sepsis and septic shock. DESIGN: Prospective randomized, placebo-controlled, multiple-center trial. SETTING: Eleven intensive care units in Germany. PATIENTS: Patients were 249 patients with severe systemic inflammatory response syndrome, sepsis, and septic shock and an Acute Physiology and Chronic Health Evaluation (APACHE) III score >70. INTERVENTIONS: Patients received 1000 microg of sodium-selenite as a 30-min bolus injection, followed by 14 daily continuous infusions of 1000 microg intravenously, or placebo. MEASUREMENTS AND MAIN RESULTS: The primary end point was 28-day mortality; secondary end points were survival time and clinical course of APACHE III and logistic organ dysfunction system scores. In addition, selenium levels in serum, whole blood, and urine as well as serum glutathione-peroxidase-3 activity were measured. From 249 patients included, 11 patients had to be excluded. The intention-to-treat analysis of the remaining 238 patients revealed a mortality rate of 50.0% in the placebo group and 39.7% in the selenium-treated group (p = .109; odds ratio, 0.66; confidence interval, 0.39-1.1). A further 49 patients had to be excluded before the final analysis because of severe violations of the study protocol. In the remaining 92 patients of the study group, the 28-day mortality rate was significantly reduced to 42.4% compared with 56.7% in 97 patients of the placebo group (p = .049, odds ratio, 0.56; confidence interval, 0.32-1.00). In predefined subgroup analyses, the mortality rate was significantly reduced in patients with septic shock with disseminated intravascular coagulation (n = 82, p = .018) as well as in the most critically ill patients with an APACHE III score > or =102 (>75% quartile, n = 54, p = .040) or in patients with more than three organ dysfunctions (n = 83, p = .039). Whole blood selenium concentrations and glutathione peroxidase-3 activity were within the upper normal range during selenium treatment, whereas they remained significantly low in the placebo group. There were no side effects observed due to high-dose sodium-selenite treatment. CONCLUSIONS: The adjuvant treatment of patients with high-dose sodium-selenite reduces mortality rate in patients with severe sepsis or septic shock.