Effect of magnesium on blood pressure.

Twenty patients receiving long term diuretic treatment for arterial hypertension (18 patients) or congestive heart failure (two patients) received magnesium supplementation as aspartate hydrochloride 15 mmol/day for six months. Both systolic and diastolic pressures decreased significantly, by a mean of 12/8 mm Hg. No significant changes were recorded in plasma or urinary electrolytes except for magnesium, 24 hour urinary volumes, or body weight after treatment. The effect of magnesium on blood pressure may be direct or through influences on the internal balance of potassium, sodium, and calcium.     

Single dose oral treatment in urinary schistosomiasis: a double blind trial.

A double blind trial of three oral preparations given in single doses for the treatment of Schistosoma haematobium infection was carried out in schoolchildren; selection was biased towards those who excreted large quantities of eggs. Praziquantel 40 mg/kg was the most effective drug giving a greater than 97% reduction in egg output six months after treatment; combined treatment with niridazole 25 mg/kg and metrifonate 10 mg/kg gave a reduction of greater than 92% and metrifonate 10 mg/kg alone a reduction of greater than 86%. Fewer children continued to have moderate to heavy infections (excretion greater than 124 ova/10 ml urine) six months after treatment with praziquantel (5%) and the combined regimen (7%) than with metrifonate (16%). Though our findings show that praziquantel appears to be the most effective and convenient drug available for individuals with S haematobium infection, the combined regimen is a cheaper alternative for treatment where cost is important and parasitological cure not an essential objective.     

Comparison between a slow-release oral preparation of bromocriptine and regular bromocriptine in patients with hyperprolactinemia: a double blind, double dummy study.

The efficacy and tolerability of a slow-release preparation of bromocriptine (Parlodel SRO) were compared to those of conventional bromocriptine (Parlodel R) in a double blind, double dummy study of 12 hyperprolactinemic women (plasma PRL 81.3 +/- 4.73, ng/ml mean +/- SEM). For 2 weeks, the patients received 2.5 mg b.i.d. Parlodel R or 5 mg once daily Parlodel SRO; for the following 2 weeks, the dose of the drugs was doubled. The patients were then treated, in an open study, with 2.5-10 mg daily Parlodel SRO for 6 months. Both preparations caused a prompt and sharp PRL fall. Hormone levels remained inhibited over the whole month of observation with both preparations. Daily PRL profiles were very close with either drug although morning PRl levels were slightly higher during Parlodel SRO than during Parlodel R administration. Doubling the doses of the two drugs did not result in further significant lowering of PRL values. During the 6-month study with Parlodel SRO, plasma PRL further decreased and normalized in 11 of 12 patients. Clinical improvement occurred in the majority of cases. Tolerability of Parlodel SRO appeared to be better, though without statistically significant differences, than that of Parlodel R. Side effects were less important with the former compound in their number, severity and duration. In conclusion, thanks to its favourable pharmacological profile, Parlodel SRO appears to be a valuable alternative to regular bromocriptine in the management of hyperprolactinemia.     

Treatment of the restless legs syndrome with carbamazepine: a double blind study.

One hundred and seventy four patients suffering from the restless legs syndrome were examined in a double blind, between patient, placebo controlled study in general practice for five weeks to investigate the effects of carbamazepine and placebo on the syndrome. The syndrome was more common among middle aged women with relatively low systolic blood pressure. The median haemoglobin concentration was about average for the population, but the severity of the symptoms seemed to increase with decreasing concentrations of haemoglobin. Both placebo and carbamazepine showed a significant therapeutic effect (p less than 0.01). Carbamazepine was significantly more effective than placebo (p less than or equal to 0.03). The significant therapeutic effect of placebo in restless legs showed that only double blind controlled trials can confirm the efficacy of suggested treatments.     

Sulphasalazine in ankylosing spondylitis: a double blind controlled study in 60 patients.

Sulphasalazine has been reported to be effective in ankylosing spondylitis with peripheral arthritis, but its efficacy in spondylitis is unknown. Thus 60 patients with active ankylosing spondylitis without peripheral arthritis or gastrointestinal symptoms were randomly allocated to one of two therapeutic groups. One group received 2 g sulphasalazine daily for six months and the other a placebo. Thirteen patients (six given placebo and seven given sulphasalazine) dropped out of the trial and were considered to be treatment failures. After six months'' follow up efficacy was rated as good or very good by 15 of the 30 patients given sulphasalazine and by only six of the 30 given placebo (p less than 0.02). Furthermore, in the patients given sulphasalazine the daily consumption of non-steroidal anti-inflammatory drugs, functional index, and plasma IgG concentrations had fallen significantly. These data suggest that sulphasalazine may be a safe and effective treatment for spondylitis in ankylosing spondylitis.     

Effect of enterocoated cholestyramine on bowel habit after ileal resection: a double blind crossover study.

Ileal resection causes malabsorption of bile acid; the increased load of bile acids in the colon induces increased secretion of salt and water and hence diarrhoea. A study was carried out to test the effect of an enterocoated cholestyramine tablet designed to disintegrate in the colon and sequester the bile acids there, thereby minimising diarrhoea induced by bile acids while having no effect on malabsorption of bile acid and jejunal fat absorption. The study comprised 14 patients who had undergone ileal resection of 40-150 cm for Crohn''s disease. A double blind crossover trial was performed with placebo and cholestyramine enterocoated with cellulose acetate phthalate. During treatment with cholestyramine the daily faecal output decreased, the number of defecations each week decreased, and the intestinal transit time increased. Acceptability of the tablets was high, in contrast with general clinical experience with cholestyramine powder. No change was observed in the total faecal output of bile acids or fat. Cholestyramine tablets caused a reduction in diarrhoea without noticeably interfering with the metabolism of fat or bile acid.     

Symptoms of low blood pressure: a population study.

OBJECTIVE--To establish whether an association exists between blood pressures in the "low normal" range and common symptoms such as tiredness, dizziness, headache, and palpitation, as suggested by French and German medical practice but not English or American medical practice. DESIGN--Cross sectional population based survey (the health and lifestyle survey) of blood pressure measurements and self reported common symptoms. Results were analysed by combined stratification and logistic regression. SUBJECTS--7383 (82%) Adults aged 18 and over chosen from the electoral register in England, Wales, and Scotland for the health and lifestyle survey, in whom satisfactory physiological measurements were taken, from 9003 in the interviewed sample. MAIN OUTCOME MEASURES--Body mass index, smoking, social class, exercise, self declared physical illnesses, hours slept, use of drugs, and psychological illness as determined with the general health questionnaire assessed as potential confounders. RESULTS--True confounders were sex, age, taking of drugs, physical illness, exercise, and body mass index. A negative association was found between systolic blood pressure and self reported tiredness and feeling faint, which persisted after adjustment for the confounders. The association was strongest in women aged under 50. A negative association between systolic blood pressure and headache and a positive association between systolic blood pressure and palpitation were explained by confounding by age. CONCLUSIONS--Systemic hypotension is associated with persistent tiredness but treatment is not suggested as either possible or necessary. Instead, low blood pressures may be associated with opposite effects on mortality contrasted with morbidity.     

Lack of effect of acute oral ingestion of vitamin C on oxidative stress, arterial stiffness or blood pressure in healthy subjects

Vitamin C is a potent antioxidant in vitro and has been reported to act as a vasodilator, possibly by increasing nitric oxide bioavailability. This study examined the antioxidant and vascular effects of a single large oral dose of vitamin C in 26 healthy human volunteers. Haemodynamic and oxidative DNA and lipid damage markers were measured for 8 h following an oral dose of 2 g vitamin C or placebo. Vitamin C had no effect on vasodilation (measured by augmentation index (mean change=0.04%, 90% CI=- 2.20% to 2.28%) or forearm blood flow (-0.19%/min (-0.68, 0.30)), in comparison to placebo) or on several markers of oxidative stress including DNA base oxidation products in blood cells, 8-hydroxy-2'-deoxyguanosine (8O HdG) in urine (0.068 (-0.009, 0.144)) or urinary or plasma total F(2)-isoprostanes (-0.005 ng/ml (-0.021, 0.010), -0.153 ng/mg (-0.319, 0.014), respectively).     

Lack of effect of acute oral ingestion of vitamin C on oxidative stress,arterial stiffness or blood pressure in healthy subjects

Vitamin C is a potent antioxidant in vitro and has been reported to act as a vasodilator, possibly by increasing nitric oxide bioavailability. This study examined the antioxidant and vascular effects of a single large oral dose of vitamin C in 26 healthy human volunteers. Haemodynamic and oxidative DNA and lipid damage markers were measured for 8 h following an oral dose of 2 g vitamin C or placebo. Vitamin C had no effect on vasodilation (measured by augmentation index (mean change=0.04%, 90% CI=? 2.20% to 2.28%) or forearm blood flow (?0.19%/min (?0.68, 0.30)), in comparison to placebo) or on several markers of oxidative stress including DNA base oxidation products in blood cells, 8-hydroxy-2’-deoxyguanosine (8O HdG) in urine (0.068 (?0.009, 0.144)) or urinary or plasma total F₂-isoprostanes (?0.005 ng/ml (?0.021, 0.010), ?0.153 ng/mg (?0.319, 0.014), respectively).     

Effect of long-term treatment with salmeterol on asthma control: a double blind,randomised crossover study.

OBJECTIVES: To determine the effect of adding salmeterol 50 micrograms twice daily for six months to current treatment in subjects with asthma who control their inhaled corticosteroid dose according to a management plan. DESIGN: A double blind, randomised crossover study. SETTING: Nottingham. SUBJECTS: 101 subjects with mild or moderate asthma taking at least 200 micrograms twice daily of beclomethasone dipropionate or budesonide. INTERVENTIONS: Salmeterol 50 micrograms twice daily and placebo for six months each, with a one month washout. Subjects adjusted inhaled steroid dose according to guidelines. MAIN OUTCOME MEASURE: Reduction in inhaled steroid use, exacerbations of asthma, and use of oral steroids. RESULTS: Data were available for 87 subjects. When compared with placebo salmeterol treatment was associated with a 17% reduction in inhaled steroid use (95% confidence interval 12% to 22%) with no significant difference in the number of subjects who had an exacerbation (placebo 25%, salmeterol 16%) or use of oral steroids. For secondary end points salmeterol treatment was associated with higher morning and evening peak expiratory flow and forced expiratory volume in one second; a reduction in symptoms, bronchodilator use and airway responsiveness to methacholine; and no effect on serum potassium concentration, 24 hour heart rate, or the final forced expiratory volume in one second achieved during a salbutamol dose-response study. CONCLUSIONS: In subjects who adjusted their inhaled steroid treatment according to guidelines the addition of salmeterol 50 micrograms twice daily was associated with a reduction in inhaled steroid use and improved lung function and symptom control.     

Efficacy of a small single dose of oral dexamethasone for outpatient croup: a double blind placebo controlled clinical trial.

OBJECTIVE--To assess the efficacy of a single dose of oral dexamethasone 0.15 mg/kg in children with mild croup not admitted to hospital. DESIGN--Double blind, randomised, placebo controlled clinical trial. SETTING--The emergency department of a tertiary paediatric hospital. SUBJECTS--100 children aged 4-122 months presenting with mild croup. INTERVENTION--A single oral dose of dexamethasone 0.15 mg/kg or placebo. MAIN OUTCOME MEASURE--Return to medical care with ongoing croup. RESULTS--Baseline characteristics of the two treatment groups were similar. Eight children (all from the placebo group) returned to medical care with ongoing croup, one being admitted. There was no reported difference in duration of croup symptoms, duration of viral symptoms, or rate of return to medical care for other reasons. CONCLUSION--Oral dexamethasone in a dose of 0.15 mg/kg is effective in reducing return to medical care with ongoing croup in children with mild croup.     

Comparison of injection techniques for shoulder pain: results of a double blind,randomised study.

Seventy seven patients with soft tissue shoulder lesions including adhesive capsulitis and disorders of the rotator cuff and acromioclavicular joint were admitted to a trial comparing two different methods of corticosteroid injection with local anaesthetic in a randomly allocated double blind study. The method of anatomical injection after diagnosis by the technique of selective tissue tension gave 60% success compared with the method using tender or trigger point localisation, giving 20% success (p less than 0.001).     

Comparison of intravenous infusions of iloprost and oral nifedipine in treatment of Raynaud's phenomenon in patients with systemic sclerosis: a double blind randomised study.

OBJECTIVE--To compare the long term effects of short term intravenous infusions of iloprost with those of oral nifedipine in patients with Raynaud''s phenomenon associated with systemic sclerosis. DESIGN--Double blind, placebo controlled, randomised group comparison. SETTING--Dermatology outpatient clinic. PATIENTS--Twenty three patients with Raynaud''s phenomenon associated with well documented systemic sclerosis (American Rheumatism Association criteria) and with typical abnormalities in fingernail folds on capillaroscopy. INTERVENTIONS--Twelve patients were randomised to receive intravenous infusions of iloprost starting at 0.5 ng/kg/min and increased by 0.5 ng/kg/min every 15 minutes to a maximum of 2.0 ng/kg/min for eight hours on three consecutive days with a further single infusion at week 8. Placebo capsules were given concurrently. Eleven patients were randomised to receive nifedipine, starting at 30 mg daily and increased to 60 mg daily after four weeks for another 12 weeks. Infusions of placebo were given in the same manner as the infusions of iloprost. One patient from each group withdrew because of social reasons and three patients receiving nifedipine withdrew because of side effects. END POINT--Reduction in number, duration, and severity of attacks of Raynaud''s phenomenon, reduction in number of digital lesions, increase in digital blood flow. MEASUREMENTS AND MAIN RESULTS--Measurements were taken at 0, 4, 8, 12, and 16 weeks. Both regimens produced a reduction in the number, duration, and severity of attacks of Raynaud''s phenomenon. The mean (SE) number of digital lesions was reduced with iloprost (from 3.5 (1.6) to 0.6 (0.3] and with nifedipine (from 4.3 (0.8) to 1.4 (0.5] after 16 weeks. Hand temperature and digital and microcirculatory blood flow were increased with iloprost but not with nifedipine. CONCLUSION--Both iloprost and nifedipine are beneficial in the treatment of Raynaud''s phenomenon. With nifedipine, however, side effects are common. Short term infusions of iloprost provide longlasting relief of symptoms, and side effects occur only during the infusions and are dose dependent.     

Nonsymmetrical double logistic analysis of ambulatory blood pressure recordings.

We developed an asymmetric double logistic curve-fitting procedure for circadian analysis that can determine the rate of change in variables during the day-to-night separately from the night-to-day transition for use in animal studies. We now have applied this procedure to 24-h systolic (SAP) and diastolic arterial pressure (DAP) and heart rate ambulatory recordings from 302 patients. In 292 cases, all parameters showed a pattern of higher day and lower night values. In men there was a similar rate of transition between day and night or from night to day for both SAP and DAP that lasted 3-4 h, indicating a symmetrical diurnal pattern. By contrast, women showed a faster rate of decrease in mean arterial pressure in the evening compared with men (P < 0.05) and therefore showed an asymmetric diurnal SAP pattern. For both men and women, there was a markedly greater rate of morning increase in heart rate compared with the rate of evening decrease (2.2- and 1.9-fold, respectively, P < 0.001). The logistic method provided a better fit than the square-wave or the cosinor method (P < 0.001) and more appropriately detected nondippers. We conclude that analysis of ambulatory recordings by a new logistic curve-fitting method reveals more rapid reductions in evening SAP in women than men but both have two- to threefold more rapid morning rates of tachycardia. The ability of the double logistic method to determine the diurnal blood pressure rates of change independently is key to determining new markers for cardiovascular risk.     

D-camphor-crataegus berry extract combination increases blood pressure and cognitive functioning in the elderly – A randomized,placebo controlled double blind study

The present study investigated whether the D-camphor-crataegus berry extract combination Korodin^® elevates blood pressure and enhances cognitive performance in the elderly population. Eighty women aged between 50 and 80 years were examined based on a randomized, placebo controlled double blind design. Blood pressure was measured sphygmomanometrically and through continuous noninvasive recording. Cognitive performance was assessed by means of two tests measuring general information processing capacity and visuomotor speed. The administration of the drug led to a short term increase in blood pressure as well as in cognitive performance as compared to placebo. Potential physiological mechanisms of action mediating this effect, including hemodynamic alterations, sympathetic stimulation as well as improvement of cerebral metabolism are discussed.     

Moderate sodium restriction with angiotensin converting enzyme inhibitor in essential hypertension: a double blind study.

Fifteen unselected patients who had essential hypertension and whose average supine blood pressure when they were not receiving any treatment and their usual sodium intake was 162/107 mm Hg were treated with captopril 50 mg twice daily. After one month''s treatment their supine blood pressure had decreased to 149/94 mm Hg. They were then instructed to reduce their sodium intake to about 80 mmol(mEq)/day. After two weeks of moderate sodium restriction they were entered into a double blind randomised crossover study comparing the effect of 10 Slow Sodium tablets (100 mmol sodium chloride) with matching placebo tablets while continuing to take captopril and restrict sodium in their diet. After one month of taking placebo their mean supine blood pressure was 137/88 mm Hg with a urinary sodium excretion of 83 mmol/24 h, while after one month of taking Slow Sodium tablets their mean supine blood pressure was 150/97 mm Hg (p less than 0.001) with a sodium excretion of 183 mmol/24 h. The mean supine blood pressure during moderate sodium restriction therefore decreased by 9% and correlated significantly with the reduction in urinary sodium excretion. These results suggest that the combination of treatment with a moderate but practical reduction in sodium intake and an angiotensin converting enzyme inhibitor is effective in decreasing the blood pressure in patients with essential hypertension. This combined approach overcomes some of the objections that have been made to salt restriction alone and to converting enzyme inhibitors alone.