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PubMedDate not supplied

Cardiovascular indices of peripheral and central sympathetic activation.

OBJECTIVE: A number of sympathetic nervous system (SNS) parameters have been used in cardiovascular psychophysiology. This study aimed to describe the pattern and redundancy of a set of SNS parameters during peripherally induced changes of cardiac sympathetic activation and reflex modulation of central SNS control. Preejection period (PEP) was assessed as a marker of peripheral sympathetic activation. Low-frequency blood pressure variability (BPV) was assessed as an estimate of central SNS control. METHODS: Peripheral beta-sympathetic stimulation and blockade were achieved with epinephrine and esmolol hydrochloride (beta1-blockade), respectively. Changes in central SNS output were induced by loading and unloading arterial baroreceptors with norepinephrine and nitroprusside sodium, respectively. This single-blinded, crossover study in 24 healthy men also included two placebo control periods. PEP was derived from impedance cardiography and adjusted individually for heart rate. BPV was calculated by power spectral analyses of beat-to-beat heart rate and systolic blood pressure (Finapres system) data. RESULTS: PEP decreased during epinephrine infusion (-40.1 +/- 3.8 ms, p <.0001) and increased during esmolol infusion (+6.6 +/- 3.5 ms, p =.05). PEP was shortened after central SNS activation by nitroprusside (-16.8 +/- 2.9 ms, p < 0.0001). Systolic BPV in the low-frequency range (0.07-0.14 Hz, Mayer waves) increased during nitroprusside infusion (+0.44 +/- 0.19 ln mm Hg(2), p =.03) and decreased during norepinephrine infusion (-0.67 +/- 0.13 ln mm Hg(2), p < 0.0001). Low-frequency BPV did not change significantly during epinephrine or esmolol infusion. CONCLUSIONS: Our data provide empirical evidence of separable peripheral and central sympathetic response components. The combined report of low-frequency BPV and PEP gives distinct information on both central SNS control and the level of sympathetic cardiac activation achieved.

Adrenergic alpha-Agonists↗
PubMed1990

Comparison of propranolol, diltiazem, and nifedipine in the treatment of ambulatory ischemia in patients with stable angina. Differential effects on ambulatory ischemia, exercise performance, and anginal symptoms. The ASIS Study Group.

Episodes of transient myocardial ischemia during ambulatory activities are common in patients with stable coronary artery disease and who are often asymptomatic. Selection of therapy for episodes of asymptomatic ischemia is limited by a lack of direct comparative studies. To determine the most effective monotherapy for patients with stable angina and a high frequency of asymptomatic ischemic episodes, propranolol-LA (mean daily dose, 293 mg), diltiazem-SR (mean daily dose, 350 mg), nifedipine (mean daily dose, 79 mg) were each compared with placebo, each for 2 weeks, in a randomized, double-blinded, crossover trial. Entry criteria were a positive exercise treadmill test during placebo therapy characterized by 1.0 mm or more ST segment depression and angina pectoris, and six or more episodes of transient ST segment depression of 1.0 mm or more on a 48-hour ambulatory electrocardiogram. One hundred ninety-four patients were screened, 63 were eligible and received randomized therapy, of which 56 patients completed at least two of the four treatment periods and were included in an intent-to-treat analysis. Fifty patients completed all four treatment phases and were included in the protocol-completed analysis. Anti-ischemia efficacy was assessed by 48-hour ambulatory electrocardiographic monitoring, exercise treadmill tests, and anginal diaries. Ninety-four percent of all episodes of ambulatory ischemia were asymptomatic. Compared with placebo, only propranolol was associated with a marked reduction in all manifestations of asymptomatic ischemia during ambulatory electrocardiographic monitoring (2.3 versus 1.0 episodes/24 hr; mean duration of ischemia per 24 hours, 43.6 versus 5.7 minutes; both p less than 0.0001). Diltiazem's reduction of the frequency of episodes compared with placebo (2.3 versus 1.9 episodes/24 hr) was associated with a trend (p = 0.08) in the protocol-completed analysis and with a significant reduction in the intent-to-treat analysis (p = 0.03). Nifedipine had no significant effect on any measured variable of ambulatory ischemia. The dosages of medication used may have been excessive for some patients, and a more beneficial effect may have been evident at a lower dose. In contrast to the marked effects of the active agents on ambulatory asymptomatic ischemia, the effects on exercise performance and angina pectoris were slight. The active agents modestly improved treadmill exercise duration time until 1 mm ST segment depression (3%), and only propranolol and diltiazem had significant effects. Only diltiazem significantly prolonged the total exercise time. Anginal frequency was significantly decreased by both propranolol and diltiazem.(ABSTRACT TRUNCATED AT 400 WORDS)

Angina Pectoris↗
PubMed1978

A method for the measurement of tremor, and a comparison of the effects of tocolytic beta-mimetics.

A method permitting measurement of finger tremor as a displacement-time curve is described, using a test system with simple amplitude calibration. The coordinates of the inversion points of the displacement-time curves were transferred through graphical input equipment to punched tape. By means of a computer program, periods and amplitudes of tremor oscillations were calculated and classified. The event frequency for each class of periods and amplitudes was determined. The actions of fenoterol-hydrobromide, ritodrin-HCl and placebo given to 10 healthy subjects by intravenous infusion in a double-blind crossover study were tested by this method. At therapeutic doses both substances raised the mean tremor amplitude to about three times the control level. At the same time, the mean period within each class of amplitudes shortened by 10--20 ms, whereas the mean periods calculated from all oscillations together did not change significantly. After the end of fenoterol-hydrobromide infusion, tremor amplitudes decreased significantly faster than those following ritodrin-HCl infusion.

Computers↗
PubMed1986

Comparison of nicardipine and propranolol for chronic stable angina pectoris.

In a double-blind, randomized, crossover clinical trial, a new calcium antagonist, nicardipine (90 mg/day in 3 divided doses), was compared with propranolol (120 mg/day in 3 divided doses) in 25 patients with chronic stable angina. The mean weekly frequency of angina episodes decreased from 7.8 +/- 1.2 (+/- standard error of the mean) with placebo to 3.8 +/- 1.2 with nicardipine treatment and 3.5 +/- 1 with propranolol treatment (p less than 0.001). With exercise testing, 5 patients receiving nicardipine and 3 receiving propranolol had no angina or ST-segment changes. Comparing paired samples of both drugs with placebo, significant improvement occurred in exercise duration (nicardipine, 1.3 +/- 0.3 minutes, p less than 0.001; propranolol, 1.0 +/- 0.4 minutes, p less than 0.01), time to onset of angina (nicardipine, 1.5 +/- 0.4 minutes, p less than 0.001; propranolol, 1.5 +/- 0.5 minutes, p less than 0.001), maximal ST-segment changes (nicardipine, 0.7 +/- 0.1 mm, p less than 0.01; propranolol, 0.06 +/- 0.1 mm, p less than 0.01) and time to 1 mm of ST depression (nicardipine, 2.5 +/- 0.4 minutes, p less than 0.01; propranolol, 2.0 +/- 0.3 minutes, p less than 0.01). One patient receiving propranolol and 2 receiving nicardipine withdrew from the study because of transient side effects. Mild side effects occurred in 10 patients receiving propranolol and 5 receiving nicardipine. Nicardipine proved to be safe and effective for patients with chronic stable angina; it had fewer side effects than propranolol in the doses used.

Adult↗
PubMed1989

Antihypertensive effect of diltiazem in a slow-release formulation for mild to moderate essential hypertension.

The antihypertensive efficacy and frequency of adverse reactions following administration of diltiazem in a new slow-release formulation were compared with placebo in 34 patients with mild to moderate essential hypertension in a randomized, double-blind, crossover study. After 6 weeks of treatment with diltiazem (240 or 360 mg/day), average supine blood pressure (BP) decreased from 165 +/- 21/101 +/- 5 mm Hg at baseline to 152 +/- 16/93 +/- 4 mm Hg compared with 160 +/- 19/100 +/- 7 mm Hg with placebo (p less than 0.01/p less than 0.001). Standing BP decreased from 162 +/- 20/107 +/- 6 mm Hg at baseline to 150 +/- 14/101 +/- 5 mm Hg compared to 159 +/- 18/107 +/- 8 mm Hg with placebo (p less than 0.01/p less than 0.001). The supine heart rate after diltiazem was 65 +/- 7 beats/min and after placebo 69 +/- 9 beats/min (p less than 0.01). There were no hematologic side effects. Only minor differences between diltiazem and placebo were observed in some of the biochemical laboratory values. Four patients were withdrawn due to side effects during treatment with diltiazem and 2 with placebo. Diltiazem in a slow-release formulation given twice a day lowered blood pressure significantly as monotherapy in patients with mild to moderate hypertension and was well tolerated.

Adult↗
PubMed2003

Contractions and expansions of CAG/CTG trinucleotide repeats occur during ectopic gene conversion in yeast, by a MUS81-independent mechanism.

CAG/CTG trinucleotide repeat tracts expand and contract at a high rate during gene conversion in Saccharomyces cerevisiae. In order to characterize the mechanism responsible for such rearrangements, we built an experimental system based on the use of the rare cutter endonuclease I-SceI, to study the fate of trinucleotide repeat tracts during meiotic or mitotic (allelic or ectopic) gene conversion. After double-strand break (DSB) induced meiotic recombination, (CAG)(98) and (CAG)(255) are rearranged in 5% and 52% of the gene conversions, respectively, with similar proportions of contractions and expansions. No evidence of a meiotic hot spot activity associated with trinucleotide repeats could be found. When gene conversion is induced by a DSB during mitotic growth of the cells, no rearrangement of the repeat tracts is detected when the donor sequence is allelic to the recipient site of the DSB. However, when the donor sequence is at an ectopic location, frequent contractions and expansions of the repeat tract are found. No crossing-over associated with gene conversion could be detected. Mutants for the MUS81 gene, involved in the resolution of recombination intermediates, show a frequency of rearrangements identical with that of the wild-type strain. We concluded that trinucleotide repeat rearrangements occur frequently during ectopic but not during allelic recombination, by a mechanism that does not require crossover formation.

Alleles↗
PubMed2006

Is an anal plug useful in the treatment of fecal incontinence in children with spina bifida or anal atresia?

PURPOSE: We evaluated the efficacy and tolerance of the Conveen anal plug in children with spina bifida or anal atresia with persistent fecal incontinence necessitating diapers despite bowel management. MATERIALS AND METHODS: Seven 4 to 12-year-old patients with high congenital imperforate anus and 9 who were 6 to 13 years old with spina bifida, no mental retardation and no involuntary urine loss on clean intermittent catheterization were included in the study. During a prospective, 6-week crossover descriptive study after a test period to find the most comfortable plug with a diameter of 37 or 45 mm patients and parents completed a diary with the number of soiling episodes, stool frequency, stool consistency and the number of diapers used during 3 weeks without and with the plug, respectively. They provided a final assessment of the device. RESULTS: Two of the 7 patients with congenital imperforate anus discontinued use because of pain and discomfort, 1 had a decrease in soiling episodes and 4 achieved full continence and needed no diapers while using 2 plugs daily (range 1 to 4). All patients preferred the smaller plug. Two of the 9 patients with spina bifida always lost the plug within 1 hour after introduction, 5 had a decrease in soiling episodes but continued to need diapers and 2 achieved full continence using 2 plugs daily (range 1 to 4). All patients preferred the larger plug. CONCLUSIONS: The Conveen anal plug is an adjuvant treatment option for fecal incontinence in children with congenital imperforate anus or spina bifida, enabling a minority to stop using diapers. The Conveen anal plug is not a universal solution for fecal incontinence problems in these patients.

Anus, Imperforate↗
PubMed1983

Yeast recombination: the association between double-strand gap repair and crossing-over.

In previous experiments, we have used yeast transformation to study the recombinogenic repair of double-strand breaks and gaps. A plasmid containing a double-strand gap within sequences homologous to the yeast genome integrates efficiently by crossing-over. During the process of integration, the double-strand gap is repaired, using chromosomal information as a template. This repair reaction results in the transfer of genetic information from one DNA duplex to another and is therefore a pathway for gene conversion. Because meiotic gene conversion is associated with a high frequency (up to 50%) of crossing-over, we wished to determine the degree of association of double-strand gap repair with crossing-over. Only the class of repair events resulting in crossovers (plasmid integration) were detected in our earlier experiments with nonreplicating plasmids. In this paper, we describe the outcome of double-strand gap repair in plasmids that are capable of autonomous replication and therefore allow recovery of both crossover and noncrossover products. After the correct repair of a double-strand gap, we recover approximately equal numbers of integrated and nonintegrated plasmids. Thus, gene conversion by double-strand gap repair can occur either with or without crossing-over, and it is similar in this respect to meiotic gene conversion. Circularization of linear plasmid DNA by ligation is also observed, suggesting that yeast has an additional repair pathway for double-strand breaks that is independent of recombination. Gap repair on replicating plasmids permits rapid cloning of chromosomal alleles.

Alleles↗
PubMed2003

Temporal factors and the prevalence of transient exposures at the time of an occupational traumatic hand injury.

Temporal factors and the prevalence of exposure to transient risk factors for occupational traumatic hand injury were analyzed among 1166 subjects participating in a case-crossover study. Temporal factors included time of injury and elapsed time to injury since the start of the work shift. Transient exposures included work equipment, work practice, and worker-related factors. The highest frequency of injury was observed from 08:00 am to 12:00 pm (54.6%), with a peak from 10:00 to 11:00 am (14.9%). The median time into the work shift for injury was 3.5 hours. Subjects injured 2 to 3 hours into their work shift most often reported using a machine, tool, or work material that performed differently than usual (23.9%). These results suggest that acute hand injuries occur earlier in the workday and safety programs should place increased vigilance on these times.

Accidents, Occupational↗
PubMed2000

Sgs1 helicase activity is required for mitotic but apparently not for meiotic functions.

The SGS1 gene of Saccharomyces cerevisiae is a homologue for the Bloom's syndrome and Werner's syndrome genes. The disruption of the SGS1 gene resulted in very poor sporulation, and the majority of the cells were arrested at the mononucleated stage. The recombination frequency measured by a return-to-growth assay was reduced considerably in sgs1 disruptants. However, double-strand break formation, which is a key event in the initiation of meiotic DNA recombination, occurred; crossover and noncrossover products were observed in the disruptants, although the amounts of these products were slightly decreased compared with those in wild-type cells. The spores produced by sgs1 disruptants showed relatively high viability. The sgs1 spo13 double disruptants sporulated poorly, like the sgs1 disruptants, but spore viability was reduced much more than with either sgs1 or spo13 single disruptants. Disruption of the RED1 or RAD17 gene partially alleviated the poor-sporulation phenotype of sgs1 disruptants, indicating that portions of the population of sgs1 disruptants are blocked by the meiotic checkpoint. The poor sporulation of sgs1 disruptants was complemented with a mutated SGS1 gene encoding a protein lacking DNA helicase activity; however, the mutated gene could suppress neither the sensitivity of sgs1 disruptants to methyl methanesulfonate and hydroxyurea nor the mitotic hyperrecombination phenotype of sgs1 disruptants.

Adenosine Triphosphatases↗
PubMed1986

The evolutionarily conserved repetitive sequence d(TG.AC)n promotes reciprocal exchange and generates unusual recombinant tetrads during yeast meiosis.

We have studied the genetic behavior of the alternating copolymer d(TG.AC)n inserted into a defined position in the genome of the yeast Saccharomyces cerevisiae. When d(TG.AC)n sequences were present at the HIS3 locus on homologous chromosomes, diploid cells undergoing meiosis generated an excess of tetrads containing reciprocally recombined products with crossover points close to the repetitive DNA insert. Most of these tetrads exhibited gene conversion of a d(TG.AC)n insert. However, the insertion of d(TG.AC)n sequences had no effect on the frequency of gene conversion of closely linked marker genes. Surprisingly, when d(TG.AC)n sequences were present on only one homolog at the HIS3 locus, one-half of the tetrads exhibiting nonparental segregation for marker genes that flanked the repetitive DNA insert were very unusual and appeared to have arisen by multiple recombination events in the vicinity of the d(TG.AC)n insert. Similar multiply recombinant tetrads were seen in crosses in which d(TG.AC)n sequences were present on both homologs. Combined, the data strongly suggest that d(TG.AC)n sequences significantly enhance reciprocal meiotic recombination and may be important in causing multiple recombination events to occur within a relatively small region of the yeast chromosome. Molecular evidence is presented that clearly documents the postmeiotic segregation of an 80-base stretch of d(TG.AC)n.

Biological Evolution↗
PubMed1993

Erythromycin effects on gastric emptying, antral motility and plasma motilin and pancreatic polypeptide concentrations in anorexia nervosa.

In primary anorexia nervosa, gastric motility is often impaired and ensuing symptoms further discourage eating. Prokinetic agents have been shown to accelerate gastric emptying in affected patients. This study investigated whether emptying of a radiolabelled semisolid 1168 kJ meal and antral contractility were enhanced by intravenous erythromycin. Eight women and two men with anorexia nervosa (21-46 years, 50-75% of ideal body weight) received 200 mg erythromycin or placebo under crossover double blind conditions. Gastric emptying and antral contractility were recorded scintigraphically for 90 minutes. In addition, plasma motilin and pancreatic polypeptide concentrations were determined. With placebo, antral contractions were of regular 3 cycles/minute frequency. With erythromycin, less frequent and partly arrhythmic long duration contractions set in and emptying was accelerated: after 90 minutes, the activity remaining in the stomach was markedly less than with placebo in all patients (Sign test, p < 0.002). Basal motilin and pancreatic polypeptide concentrations were normal and showed a normal response to the meal in all patients. Motilin concentrations decreased slightly more and pancreatic polypeptide concentrations increased markedly more with erythromycin than with placebo, possibly because the meal reached the intestine earlier. In conclusion, erythromycin accelerated emptying markedly and in most patients induced an antral motor activity characterised by long duration contractions occurring at often irregular intervals.

Adult↗
PubMed1989

The molecular basis of beta thalassaemia in Bulgaria.

Bulgaria is in a geographical area where beta thalassaemia is relatively common. The frequency of carriers is 2 to 3% of the population. Data on the molecular characteristics of the disorder were obtained from the study of 33 homozygous patients and 57 beta thalassaemia carriers. As in other Mediterranean ethnic groups, haplotype I and the splicing mutation in IVS-1 nt 110 are the most common. Haplotype V is second in frequency and is associated with three different mutations. The second most common mutation, beta null 39, is found in association with haplotype II in 80% of cases. A rare haplotype, possibly resulting from a crossover between a haplotype II and a haplotype V chromosome, was found in two thalassaemia carriers in association with frameshift 6. Altogether four mutations (IVS-1 nt 110, beta null 39, frameshift 6, and IVS-1 nt 6) account for 67% of the thalassaemia chromosomes. Their detection would permit direct fetal DNA analysis in 84% of the families studied (45% fully informative). RFLP analysis (haplotype plus AvaII psi beta) is 100% informative in 79% of the high risk families.

Base Sequence↗
PubMed2003

Options for the prevention and management of acute chemotherapy-induced nausea and vomiting in children.

The current standard of care with respect to preventing acute chemotherapy-induced nausea and vomiting (CINV) in children includes the administration of a 5-HT(3) antagonist with or without a corticosteroid, depending on the emetogenicity of the chemotherapy to be given. Problems in assessing the emetogenicity of chemotherapy regimens and nausea severity in children may influence the degree of success of CINV prophylaxis. Nevertheless, the majority of children who receive chemotherapy today experience moderate to complete control of acute CINV when given appropriate antiemetic prophylaxis. If children vomit or experience nausea despite appropriate prophylaxis, then measures must be taken to treat these symptoms since these children are likely to go on to experience delayed or anticipatory CINV. However, appropriate selection of interventions to treat acute CINV in children is limited by the lack of rigorous evidence to support one approach over another. Lorazepam is suggested as an immediate agent for the treatment of acute CINV. Doses and frequencies of the 5-HT(3) antagonist and corticosteroid administered for initial prophylaxis should also be maximized. Further treatment must be tailored to the circumstances and preferences of each child and family. Options include crossover to another 5-HT(3) antagonist, or administration of an adjunctive antiemetic such as metopimazine, low dose metoclopramide, domperidone, alizapride, nabilone, scopolamine, prochlorperazine, or chlorpromazine. Complementary interventions such as acupuncture, hypnosis, counseling, or ginger may also be of benefit. Further study is required to establish optimal antiemetic strategies in children.

Acute Disease↗
PubMedDate not supplied

The importance of intensive supervision in determining the efficacy of insulin pump therapy.

The role of intensive supervision in the success of insulin pump programs was examined in six type I diabetic subjects utilizing a crossover protocol. The highly motivated volunteers who had attained euglycemia during intensive supervision had a significant increase in plasma glucose and hemoglobin A1c concentrations during the period when supervision by the medical team and frequency of self blood glucose monitoring decreased. Intensive supervision is a critical feature in ensuring maximal efficacy of insulin pump therapy. The importance of such supervision may be even greater in less motivated and adherent patients.

Blood Glucose↗
PubMed1998

Prostaglandin analog mechanisms are not effective in refractory chronic cluster headache.

Prostaglandin E analogs have been shown to be effective in the treatment of refractory trigeminal neuralgia in patients with multiple sclerosis. Prostaglandin E inhibits the functions of T lymphocytes which are involved in the pathophysiology of cluster headache. Therefore, a double-blind, placebo-controlled, crossover study on the efficacy of misoprostol in chronic refractory cluster headache was performed. Eight patients were treated with 600 micrograms misoprostol and with placebo for a 2-week period. No differences in attack frequency, intensity, global impression, and side effects could be detected, suggesting that prostaglandin E analogs are not effective in the treatment of chronic cluster headache.

Adult↗
PubMedDate not supplied

Efficacy of Terminalia arjuna in chronic stable angina: a double-blind, placebo-controlled, crossover study comparing Terminalia arjuna with isosorbide mononitrate.

BACKGROUND: Terminalia arjuna, an Indian medicinal plant, has been reported to have beneficial effects in patients with ischemic heart disease in a number of small, open studies. The need for a double-blind, randomized, placebo-controlled study with adequate sample size has long been felt. The bark extract (IPC-53) contains acids (arjunic acid, terminic acid), glycosides (arjunetin arjunosides I-IV), strong antioxidants (flavones, tannins, oligomeric proanthocyanidins), minerals. etc. and exhibits antifailure and anti-ischemic properties. METHODS AND RESULTS: Fifty-eight males with chronic stable angina (NYHA class II-III) with evidence of provocable ischemia on treadmill exercise test received Terminalia arjuna (500 mg 8 hourly), isosorbide mononitrate (40 mg/daily) or a matching placebo for one week each, separated by a wash-out period of at least three days in a randomized, double-blind, crossover design. They underwent clinical, biochemical and treadmill exercise evaluation at the end of each therapy which were compared during the three therapy periods. Terminalia arjuna therapy was associated with significant decrease in the frequency of angina and need for isosorbide dinitrate (5.69+/-6.91 mg/week v. 18.22+/-9.29 mg/week during placebo therapy, p<0.005). The treadmill exercise test parameters improved significantly during therapy with Terminalia arjuna compared to those with placebo. The total duration of exercise increased (6.14+/-2.51 min v. 4.76+/-2.38 min, p<0.005), maximal ST depression during the longest equivalent stages of submaximal exercise decreased (1.41+/-0.55 mm v. 2.21+/-0.56 mm, p<0.005), time to recovery decreased (6.49+/-2.37 min v. 9.27+/-3.39 min, p<0.005) and higher double products were achieved (25.75+/-4.81x10(3) v. 23.11+/-4.83x10(3), p<0.005) during Terminalia arjuna therapy. Similar improvements in clinical and treadmill exercise test parameters were observed with isosorbide mononitrate compared to placebo therapy. No significant differences were observed in clinical or treadmill exercise test parameters when Terminalia arjuna and isosorbide mononitrate therapies were compared. No significant untoward effects were reported during Terminalia arjuna therapy. CONCLUSIONS: Terminalia arjuna bark extract, 500 mg 8 hourly, given to patients with stable angina with provocable ischemia on treadmill exercise, led to improvement in clinical and treadmill exercise parameters as compared to placebo therapy. These benefits were similar to those observed with isosorbide mononitrate (40 mg/day) therapy and the extract was well tolerated. Limitations of this study include applicability of the results to only men with chronic stable angina but not necessarily to women, as they were not studied.

Adult↗
PubMed1989

A randomised double-blind crossover study of isosorbide mononitrate and nifedipine retard in chronic stable angina.

In order to evaluate and compare the efficacy and safety of nifedipine retard and isosorbide-5-mononitrate as monotherapy in the treatment of stable angina, 18 patients with abnormal exercise electrocardiograms and angiographically proven coronary arterial disease were studied in a randomised placebo controlled double-blind crossover study comparing isosorbide 20 mg twice a day, sustained released isosorbide 40 mg once daily and nifedipine 20 mg twice a day each given for two weeks. Patients were assessed subjectively by counting the frequency of anginal attacks and glyceryl trinitrate consumed and objectively by maximal symptom-limited treadmill stress tests performed at "trough" therapeutic blood levels on the last day of each treatment period. There were no significant differences in all parameters between entry and run-out placebo. Compared to placebo, all three active treatments showed significant improvement in exercise time to 1 mm ST segment depression, amount of maximum ST segment depression and exercise duration. All three active treatments also significantly reduced the consumption of glyceryl trinitrate and frequency of anginal attacks. There were no significant differences between active treatments. Thus similar clinical improvements were produced by nifedipine retard and isosorbide, both being shown to be equally effective starting therapy for the treatment of patients with stable angina pectoris. Although anginal frequency was reduced by one third and exercise time increased residual symptoms and exercise ischaemia suggest that nifedipine retard and isosorbide may be more clinically useful in combination therapy. Neither demonstrated tolerance after two weeks of therapy.

Aged↗