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PubMed2003

Physiological coxa varus-genu valgus influences internal knee and ankle joint moments in females during crossover cutting.

This study evaluated the ankle and knee electromyographic, kinematic, and kinetic differences of 20 nonimpaired females with either neutral (group 1) or coxa varus-genu valgus (group 2) alignment during crossover cutting stance phase. Two-way mixed model ANOVA (group, session) assessed mean differences ( p<0.05) and correlation analysis further delineated relationships. During impact absorption, group 2 displayed earlier peak horizontal braking (anterior-posterior) ground reaction force timing, decreased and earlier peak internal knee extension moments (eccentric function), and earlier peak internal ankle dorsiflexion moment timing (eccentric function). During the pivot phase, group 2 displayed later and eccentrically-biased peak ankle plantar flexion moments, increased peak internal knee flexion moments (eccentric function), and later peak knee internal rotation timing. Correlation analysis revealed that during impact absorption, subjects with coxa varus-genu valgus alignment (group 2) displayed a stronger relationship between knee internal rotation velocity and peak internal ankle dorsiflexion moment onset timing ( r= -0.64 vs r = -0.26) and between peak horizontal braking ground reaction forces and peak internal ankle dorsiflexion moment onset timing ( r= 0.61 vs r= 0.24). During the pivot phase these subjects displayed a stronger relationship between peak horizontal braking ground reaction forces and peak internal ankle plantar flexion moment onset timing ( r= -0.63 vs r= -0.09) and between peak horizontal braking forces and peak internal ankle plantar flexion moments ( r= -0.72 vs r= -0.26). Group differences suggest that subjects with coxa varus-genu valgus frontal-plane alignment have an increased dependence on both ankle dorsiflexor and plantar flexor muscle group function during crossover cutting. Greater dependence on ankle muscle group function during the performance of a task that requires considerable 3D dynamic knee joint control suggests a greater need for frontal and transverse plane weight bearing tasks that facilitate eccentric ankle muscle group function to optimize injury prevention conditioning and post-surgical rehabilitation programs.

Adolescent↗

PubMed1997

Fatigue after eccentric quadriceps femoris work produces earlier gastrocnemius and delayed quadriceps femoris activation during crossover cutting among normal athletic women.

Athletic women are at greater risk of anterior cruciate ligament (ACL) injury than men. Twenty, healthy, athletic women were evaluated for the effect of preferred stance limb isokinetic quadriceps femoris and hamstring fatigue from eccentric work compared with controls on the activation onset of vastus medialis, rectus femoris, vastus lateralis, the medial hamstrings, biceps femoris, and gastrocnemius muscles. Following 3 weeks of crossover cut training, subjects were tested for fatigue effects (5 subjects/week, 3 conditions, 1 condition/day, order effect controlled) on muscle activation onsets prior to crossover cut landing heelstrike (mixed model, ANOVA, P < 0.05). Fatigue from eccentric quadriceps femoris work produced delayed vastus medialis (P = 0.03), rectus femoris (P = 0.007), and vastus lateralis (P = 0.03) activation onsets compared with control, but did not differ compared to hamstring fatigue. Neither hamstring nor quadriceps femoris fatigue produced differences (P > 0.05) in medial hamstring or biceps femoris activation onsets compared to control. Quadriceps femoris fatigue from eccentric work produced earlier gastrocnemius activation onsets (P = 0.048) than control, but did not differ for hamstring fatigue. The gastrocnemius appears to provide synergistic and compensatory dynamic knee stabilization in closed kinetic chain function during quadriceps femoris fatigue. This finding in a normal group at high risk of ACL injury while performing a maneuver with a high ACL injury risk supports gastrocnemius inclusion in knee rehabilitation and conditioning programs and suggests the need for comparative evaluations of knee injured/reconstructed subjects.

Analysis of Variance↗

PubMed2003

The effect of long-term microcrystalline chitosan therapy on plasma lipids and glucose concentrations in subjects with increased plasma total cholesterol: a randomised placebo-controlled double-blind crossover trial in healthy men and women.

OBJECTIVE: To evaluate the long-term effect of microcrystalline chitosan (MCC) on plasma lipids, especially the concentration of low-density lipoprotein (LDL) cholesterol, in subjects with a moderately increased concentration of plasma total cholesterol. METHODS: A total of 130 middle-aged men and women without severe disease and with a total cholesterol of 4.8-6.8 mmol/l and triglycerides below 3.0 mmol/l were randomised into two treatment groups. At the beginning of the 10-month trial, all participants received placebo 1.2 g twice daily during a 1-month run-in period. Subsequently, group 1 first received 1.2 g placebo twice daily for 3 months and then 1.2 g MCC twice daily for 3 months. Correspondingly, group 2 received 1.2 g MCC twice daily during the first and 1.2 g placebo twice daily during the second 3-month period. During the final 3-month follow-up period, both groups received MCC. Altogether, 83 participants completed the study. RESULTS: No difference was detected in the change in the LDL-cholesterol concentration between the treatments during the crossover trial ( P=0.98 for interaction between time period and treatment group, repeated-measures analysis of variance for crossover design). In an otherwise similar analysis, no differences were detected between the treatments in the concentrations of total cholesterol, high-density lipoprotein cholesterol, triglycerides and glucose. CONCLUSIONS: Treatment with MCC had no effect on the concentrations of plasma lipids or glucose in healthy middle-aged men and women with moderately increased plasma cholesterol concentrations.

Adjuvants, Pharmaceutic↗

PubMed1999

Assessment of analgesia in human chronic pain. Randomized double-blind crossover study of once daily repro-dose morphine versus MST continus.

OBJECTIVE: This study evaluated Repro-Dose morphine (RDM; Reliadol from Nycomed Pharma), a new once daily controlled-release morphine formulation, against twice daily MST Continuous (MST) at steady state in patients with chronic opioid responsive pain. METHODS: A randomized double-blind two-way crossover design was used to evaluate the efficacy and adverse effects of RDM once daily or MST twice daily, at the same total daily doses, in patients with chronic stable pain (dose range 20-120 mg per day). During the RDM limb of the study active drug was administered in the evening and placebo in the morning. Dextromoramide was provided as escape analgesia throughout the study. Following a 5-day screening period, during which stability of oral opioid dose was verified, patients underwent two 5-day treatment periods, (one MST, one RDM) in random sequence. Pain scores, escape analgesia requirements and side-effects were compared using data from days 3, 4 and 5 of each treatment period. Any events or medication changes occurring during the study period thought liable to influence analgesia were regarded as protocol violations. Overall assessment and period preference was assessed by direct questioning. RDM treatment was regarded as successful if the amount of escape medication required during the RDM period was equal to or less than that required during the MST period. RESULTS: Forty-seven patients were included in the study, of whom 40 completed both periods [the intention to treat (ITT) population], 31 in strict accordance with the protocol [the per protocol (PP) population]. Results were similar for both populations. There was no significant difference in pain scores or incidence of adverse events occurring during the MST and RDM periods. For the ITT population, requirements for escape medication during the RDM period were less than, equal to or greater than those recorded during the MST period for 14, 15, and 11 patients, respectively. Twenty-nine of 40 patients (72.5%) were therefore RDM treatment successes (95% confidence interval 56.1-85.4%). The percentage of patients preferring RDM (45%) combined with those with no preference (32.5%) was significantly higher than those preferring MST (22.5%; P = 0. 0003). CONCLUSIONS: Oral morphine administered as RDM once daily is at least as effective and well tolerated as MST twice daily, with over 70% of patients in this double-blind crossover study reporting that RDM was equal or superior to MST.

Administration, Oral↗

PubMed2003

Implantation of the Corinthian IQ stent into the femoropopliteal arteries using 6-F introducer sheaths in antegrade and crossover procedures: midterm results.

The aim of this study was to evaluate the technical performance of the implantation of the Corinthian IQ stent into the femoropopliteal arteries using 6-F introducer sheaths. Thirty-three lesions (24 stenoses, 9 occlusions) in 32 patients (mean age 67 years) were stented. Selective stent implantation was performed after unsatisfactory percutaneous transluminal angioplasty result with an antegrade access in 21 patients and through a crossover sheath in 11 patients. A total of 36 stents were implanted. Stent delivery was successful in all cases (stent diameter 5 or 6 mm, stent length 11-38 mm). In none of the cases was stent dislodgement from the balloon observed. Stent placement was optimal without residual stenosis in 30 cases. In 1 case the stent was chosen too short requiring implantation of a second stent. In 1 patient distal embolization was observed which was treated with catheter embolectomy. Nine-month primary and secondary patency rates were 79+/-8.7 and 86+/-7.7%, respectively. Implantation of the Corinthian IQ stent into the femoropopliteal arteries using 6-F introducer sheaths is safe in antegrade and crossover procedures.

Aged↗

PubMed2006

Early exposure to haptic feedback enhances performance in surgical simulator training: a prospective randomized crossover study in surgical residents.

BACKGROUND: In the literature of skill acquisition and transfer of skills, it often is assumed that the rate of skill acquisition depends on what has been learned in a similar context (i.e., surgical simulators providing haptic feedback). This study aimed to analyze whether the addition of haptic feedback early in the training phase for image-guided surgical simulation improves performance. METHODS: A randomized crossover study design was used, in which 38 surgical residents were randomized to begin a 2-h simulator training session with either haptic or nonhaptic training followed by crossover after 1 h. The graphic context was a virtual upper abdomen. The residents performed two diathermy tasks. Two validated tests were used to control for differences in visual-spatial ability: the BasIQ general cognitive ability test and Mental Rotation Test A (MRT-A). RESULTS: After 2 h of training, the group that had started with haptic feedback performed the two diathermy tasks significantly better (p < 0.05, unpaired t-test). Only the group that had started with haptic training significantly improved during the last 1-h session (p < 0.01, paired t-test). CONCLUSION: The findings indicate that haptic feedback could be important in the early training phase of skill acquisition in image-guided surgical simulator training.

Abdomen↗

PubMed2005

Randomized double-blind, double-dummy crossover clinical trial of oral tramadol versus rectal tramadol administration in opioid-naive cancer patients with pain.

Tramadol is commonly used as second step drug of the analgesic ladder. In circumstances where the oral route is unavailable, rectal administration of opioids might be a simple alternative. The aim of this study was to compare the analgesic activity and tolerability of tramadol by oral and rectal administration in a double-blind, double-dummy crossover trial. The study included 60 cancer patients with cancer pain no longer responsive to non-opioid drugs. Each patient initially received oral tramadol 50 mg (drops), followed by tramadol sustained release 100 mg orally, and placebo rectally, or tramadol 100 mg rectally and placebo orally, twice a day, in a randomized sequence, on each of 3 days. Patients were allowed to take 50 mg of oral tramadol by drops as needed (four doses per day, to a maximum of 400 mg/day, including the basal dose given by the oral or rectal route). Pain intensity and relief and symptom scores were recorded every day and at the end of each phase of the crossover. The mean age of the patients was 66.1 years (SD 13.5 years); 36 were female, and 44 completed both periods. Patients dropped out due to adverse effects (15 patients) and refusal (1 patient). No differences in the use of rescue dose of oral tramadol were observed between the groups. No differences in pain intensity and relief scores, or in other symptoms between the two treatments were observed. No differences in treatment efficacy as judged by the clinician (P=0.73), in patient compliance (P=0.35), or in patient satisfaction regarding treatment (P<0.35) were found. No differences in adverse effects were found between the two treatments (25.5%, 13 patients, and 20.4%, 11 patients, with oral and rectal treatment, respectively). The proportion of preferences favored oral administration for both physicians (P=0.0002) and patients (P=0.002). Rectal administration of tramadol appears a reliable, noninvasive alternative method of pain control for patients no longer responsive to non-opioid analgesics, unable to take oral tramadol.

Administration, Oral↗

PubMed2006

Red hot chili pepper and hemorrhoids: the explosion of a myth: results of a prospective, randomized, placebo-controlled, crossover trial.

PURPOSE: Spicy foods are appreciated by a large part of the world population but have been blamed for causing hemorrhoids or exacerbating their symptoms, although no epidemiologic studies have been performed supporting this hypothesis. In this double-blind, randomized, placebo-controlled, crossover trial, we have studied the effects of a single dose of red hot chili pepper on the hemorrhoidal symptoms. METHODS: Fifty patients with second-degree and third-degree symptomatic hemorrhoids were randomly assigned to take a capsule containing red hot chili powder or placebo during lunch, scoring five hemorrhoidal symptoms (bleeding, swelling, pain, itching, and burning) on a visual analog scale. After one week, crossover treatment was administered according to the same methodology. Other treatments and foods potentially related with anorectal symptoms were discontinued during the study periods. RESULTS: Patients assigned low scores to their hemorrhoidal symptoms before the study and the scores remained unchanged during the 48 hours after both placebo and chili pepper treatment, the latter showing no statistically significant effects. CONCLUSIONS: There is no scientific evidence that a spicy meal based on red hot chili pepper may worsen hemorrhoidal symptoms and, therefore, there is no reason to prevent these patients from occasionally enjoying a spicy dish if they so wish.

Adult↗

PubMed1989

Double-blind crossover versus parallel groups in hypertension.

The efficacy of antihypertensive drugs requires evaluation in clinical trials, the design of which must minimize variability (observer or patient) and order effects, eliminate bias, and include sufficient numbers of patients (i.e., have sufficient power) to allow real differences in blood pressure between patient groups to be detected at conventional levels of statistical significance. The crossover design of trial requires the successive examination of different treatments. This may result in a lengthy trial for the participant and an increase in the dropout rate. Therefore the parallel group design is usually performed for a comparison of several active drugs or drugs and placebo. This design avoids the potential problems of order and carryover effects, and when of a long duration, takes into account short-term and longer term responses to drugs. Crossover trials with limited periods of treatment for each phase can be carried out with fewer numbers of subjects and are more economical of patient resources. However, care must be taken to correct for order effects by appropriate design and to exclude carryover effects. Usually such a design only allows the investigator to comment on short-term blood pressure responses. The extrapolation of such information for longer term use of the drugs in clinical practice requires much caution.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1983

Effect of oral sustained-release nitroglycerin on exercise capacity in angina pectoris: dose-response relation and duration of action during double-blind crossover randomized acute therapy.

Ten men with documented coronary artery disease and stable exertional angina underwent a double-blind crossover study to examine the benefit and the duration of action on their symptom-limited exercise capacity of 2 doses (2.5 and 6.5 mg) of sustained-release nitroglycerin (SRNG). A multistage bicycle test was performed in the sitting position by steps of 30 W each 3 minutes until the onset of typical angina pectoris. It was performed 24 hours before the start of the study; 1 and 5 hours after administration of placebo, and repeated after 2.5 and 6.5 mg of SRNG administered in a double-blind crossover study according to a 4 successive days protocol. No differences appeared between administration of placebo (1 and 5 hours) and the results obtained at the first exercise test. The dose of 2.5 mg of SRNG was effective on the symptom-limited working capacity but only at 1 hour (+9%; p less than 0.01). The dose of 6.5 mg was more effective both at 1 hour (+25%; p less than 0.001) and at 5 hours (+27%; p less than 0.001). All patients had angina at a higher heart rate (+5 to 8%; p = NS [not significant] and p less than 0.01), whereas systolic blood pressure and double product tended to be slightly but insignificantly increased. S-T depression at the onset of angina was insignificantly changed with placebo, and 2.5 and 6.5 mg of SRNG. It is concluded that 6.5 mg of orally administered SRNG is effective during at least 5 hours, and that the magnitude of the benefit and its duration are dose-related.

Aged↗

PubMed1987

Nifedipine gastrointestinal therapeutic system in stable angina pectoris. Results of a multicenter open-label crossover comparison with standard nifedipine.

To compare the clinical efficacy and dose equivalency of standard nifedipine versus a new gastrointestinal therapeutic system (GITS) formulation of nifedipine, 98 patients with chronic stable angina pectoris participated in a 14-week, multicenter, open-label, crossover trial. All patients were administered nifedipine capsules for one month prior to study entry and continued receiving other antianginal, non-calcium blocker medications. Ninety-one patients (93 percent), 80 men and 11 women, mean age 62 +/- 1 years, completed the trial, which included two weeks receiving standard nifedipine followed by 12 weeks receiving nifedipine GITS starting at a dosage equal to the 24-hour total dose of nifedipine capsules and titrated upward as necessary. However, throughout the trial, mean nifedipine dosage was similar on nifedipine GITS compared with standard nifedipine. Angina frequency was significantly less with nifedipine GITS at Weeks 6, 10, and 14 (0.8 episodes/week) compared with baseline with standard nifedipine (1.3 episodes/week, p less than 0.05). Likewise, nitroglycerin consumption was also less at Weeks 6, 10, and 14, but only significantly less at Week 6 (nifedipine 1.2/week versus nifedipine GITS at six weeks, 0.7/week; p less than 0.05). Resting hemodynamic parameters, including systolic and diastolic blood pressure and heart rate, were not significantly different with standard nifedipine versus nifedipine GITS during the 12-week study. Total incidences of side effects were similar for both treatments (standard nifedipine, 16; nifedipine GITS, 17). However, incidence of vasodilator side effects (flushing, dizziness, and light-headedness) was significantly less frequent with nifedipine GITS (standard nifedipine, 12; nifedipine GITS, six; p less than 0.05). Thus, results from this open-label, crossover trial suggest that nifedipine GITS dosing is similar to multidose standard nifedipine with equivalent 24-hour efficacy for nifedipine GITS.

Aged↗

PubMed1995

A comparison of crossover versus parallel-group design in the evaluation of analgesic efficacy after molar extraction.

This study compares the analgesic effects of two standard combinations (Empirin with codeine versus Mersyndol) and placebo as measured by crossover versus parallel-group design. The analgesic results obtained with three groups of 12 to 13 crossed over subjects with two extractions divided into six subgroups of five to seven subjects for each sequence were qualitatively the same and statistically at least as strong as those obtained by analysis of parallel groups of 38 to 42 extractions per group. By both methods the analgesics were statistically significantly more effective than placebo. The difference between the two products was not statistically significant, although the score for Mersyndol was somewhat better by both methods of study. The crossover data did not allow judgments concerning side effects in spite of its greater efficiency in quantifying pain relief.

Acetaminophen↗

PubMed1979

A computer program for the analysis of crossover designs.

We describe a program, CROSS, which we have written to obtain potency estimates and other parameters for bioassay data from assays of crossover design. The program permits testing of all assays for statistical validity and calculates the complete analysis of variance for assays of balanced design. The form of data input and the complete documentation of assay results make this program particularly useful for anyone carrying out crossover assays on a routine basis. The analysis of variance presented is also useful for more general biological or medical situations.

Computers↗

PubMed1987

Identification of endogenous retroviral sequences as potential donors for recombinational repair of mutant retroviruses: positions of crossover points.

Mutants of Moloney murine leukemia virus carrying deletions in essential regions of the genome can revert after infection of mouse cells by recombination with endogenous retroviral sequences. We have identified cloned DNAs containing potential donor sequences for two such recombination events and determined the nucleotide sequences in the relevant regions. Comparison of these sequences with that of the original mutants and the revertant viruses allowed a determination of the crossover points that were used in formation of the revertants. Each crossover occurred in short stretches (17-24 bp) of perfect homology between the two parent sequences.

Amino Acid Sequence↗

PubMed1989

Therapy of chronic idiopathic urticaria with nifedipine: demonstration of beneficial effect in a double-blinded, placebo-controlled, crossover trial.

The efficacy of nifedipine, a calcium channel antagonist, in the treatment of chronic idiopathic urticaria, was evaluated in a double-blinded, placebo-controlled, crossover trial. Ten patients with chronic urticaria refractory to maximally tolerated doses of H1 and H2 antihistamines and in whom extensive evaluation failed to identify a cause for their urticaria were entered into the study. Patients continued with their prestudy antihistamine regimens. A study drug dosage was titrated in each patient and maintained throughout the trial. Patients were treated with placebo or nifedipine for 4 weeks and then crossed over to the other medication for 4 weeks. One patient withdrew because of unrelated medical illness, two patients withdrew after crossover to placebo because of intolerable urticaria, and seven patients completed the study. A beneficial effect of nifedipine was clearly demonstrated. Hive count, hive index, and itch index were all significantly improved at the end of 4 weeks of nifedipine treatment (p = 0.023, 0.003, and 0.003, respectively) but not placebo treatment (p = 0.194, 0.664, and 0.944, respectively). Additionally, end point hive index and itch index scores with nifedipine compared to corresponding placebo scores were significantly improved (p = 0.010 and 0.008, respectively). Nifedipine was well tolerated. Thus, when nifedipine is used as an adjunct to antihistamines, it appears to be a safe, efficacious drug for the treatment of chronic idiopathic urticaria.

Adult↗

PubMed1987

The gamma delta resolvase induces an unusual DNA structure at the recombinational crossover point.

gamma delta resolvase, a transposon-encoded protein active in site-specific recombination, induces a structural change in the DNA at the recombinational crossover point that results in enhanced intercalation of the foot-printing reagent MPE X Fe(II). The structural change correlates with the formation of a bend in the DNA: a mutant resolvase that binds to the crossover site but induces little or no bend does not promote intercalation. The properties of the mutant protein suggest that the induced structural change, which we propose is a localized kink, is required for recombination.

Crossing Over, Genetic↗

PubMed1987

The beta-delta crossover leading to the beta delta hybrid gene of hemoglobin P-Nilotic is located within 54 base-pairs of the 5' end of exon 2 or between codons 31 and 50.

The crossover region of the beta delta hybrid gene of the hemoglobin variant Hb P-Nilotic was defined in detail through cloning and sequencing of appropriate DNA segments. The crossover must have occurred without loss of bases within a 54 base-pair stretch of DNA between bases 275 and 330 (or between amino acid residues 31 and 50), indicating that the exon 1 and IVS-1 originate from beta, and exon 2, IVS-2 and exon 3 from delta. The data support the speculation that the IVS-1, in contrast to IVS-2, has no effect on the expression of this hybrid gene.

Adult↗

PubMed1995

Comparative study of efficacy and safety of low-dose diltiazem or betaxolol in combination with digoxin to control ventricular rate in chronic atrial fibrillation: randomized crossover study.

BACKGROUND: The combination therapy of low-dose diltiazem or bexatolol with digoxin can be a useful adjunct for achieving heart rate control with minimal side effects. But there has not been a study including patients with impaired left ventricular function and evaluating whether the beneficial effects of medication will be maintained during a follow-up period. OBJECTIVES: The purpose of this study was three-fold: (1) to compare the efficacy of digoxin with low-dose diltiazem and digoxin with low-dose betaxolol on randomized crossover study; (2) to evaluate whether the beneficial effects of medication will be maintained after 7 months; (3) to evaluate the safety of the combination therapy in patients with impaired left ventricular function. METHODS: We did a prospective randomized crossover study in 35 patients with chronic atrial fibrillation (AF) including 15 patients with left ventricular dysfunction. After enrollment, each patient was evaluated for heart rate, blood pressure, rate-pressure products, maximal exercise tolerance at rest and during symptom-limited treadmill test before medication, at 4 weeks after medication of digoxin (0.125-0.5 mg daily) with diltiazem (90 mg twice daily), and at 4 weeks after digoxin with betaxolol (20 mg once daily). We performed 24-h ambulatory electrocardiogram (ECG) in 15 patients at the end of each phase of treatment. We repeated symptom-limited treadmill test like above method in 15 patients at 7 months of medication. RESULTS: (1) Ventricular rates were significantly reduced in digoxin with low-dose betaxolol therapy at rest and during exercise (67 +/- 3, 135 +/- 5 (mean +/- S.E.M.) beats/min, respectively) in comparison to digoxin with low-dose diltiazem therapy (80 +/- 7, 154 +/- 5) (P < 0.05). (2) Rate-pressure products were significantly less in digoxin with low-dose betaxolol at rest and during exercise (85 +/- 4, 213 +/- 12 x 10(2) mmHg/min) than in digoxin with low-dose diltiazem therapy (105 +/- 6, 269 +/- 12) (P < 0.05). (3) Exercise capacity was significantly improved in digoxin with low-dose betaxolol (9.3 +/- 0.5 METS) or digoxin with low-dose diltiazem (9.7 +/- 0.5) in comparison to control state (8.3 +/- 0.5) (P < 0.05). (4) At 7 months evaluation, there was no significant difference between at 4 weeks and at 7 months. (5) Results on 24-h ambulatory ECG showed the same findings as on treadmill test. (6) Although side effects occurred more frequently in digoxin with low-dose betaxolol therapy, they were minimal and no patient had to withdraw medication. Worsening of left ventricular dysfunction was not observed. CONCLUSION: Our study suggested that (1) combination therapy of low-dose betaxolol with digoxin was more superior to low-dose diltiazem with digoxin in controlling ventricular rate and reducing rate-pressure products; (2) the effects controlling ventricular rate, reducing rate-pressure products and improving exercise capacity have been well maintained even after 7 months of medication with each combination therapy.

Adrenergic beta-Antagonists↗