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PubMed1994

[Comparative clinical study of Neopanpur and Creon].

The aim of the study was to compare the clinical efficacy of Neopanpur (EGIS) and Creon (Kalichemie) in patients with chronic pancreatitis. Fifteen patients were examined for 2 x 10 days. A period: Neopanpur 3 x 2, B period: Creon 10,000 3 x 2. The type of the trial was: randomized, open, crossover study. The complaints of the patients (in score), the characters of the stool (daily weight, fat content, foamy, smell), amylum tolerance test (ATT), H2-breath test, lipjodol-test, Lundh-test and Schilling-test were determined before and during the treatment periods. Both enzyme preparations could effectively decrease the anamnestic complaints, the stool frequency and characteristics together with the laboratory results of pancreatic functions. There is no clinically significant difference between the clinical efficacy of Creon and Neopanpur. Both enzyme preparations can be applied in the treatment of maldigestion in patients with chronic pancreatic insufficiency.

Adult↗
PubMed1978

Mapping of the linkage group GLO--Bf--HLA-B,C,A--PGM3. 1. Recombination frequencies.

This study confirms close linkage for the GLO--Bf--HLA-B,C,A complex, and proves linkage between the MHC loci and PGM3. For GLO--PGM3 and Bf--PGM3, respectively, loose linkage seems to be likely, and close linkage can be excluded. Our mapping data on chromosome 6 favor the hypothesis that the PGM3 locus is situated on the HLA-A side of the MHC complex. Yet fine-structure mapping should be confirmed only by segregation analyses in crossover families by testing simultaneously all of the relevant marker loci within uniform family material.

Chromosome Mapping↗
PubMed1999

Antibiotic efficacy in small intestinal bacterial overgrowth-related chronic diarrhea: a crossover, randomized trial.

BACKGROUND & AIMS: No controlled trial has examined the clinical efficacy of antibiotics in small bowel bacterial overgrowth. METHODS: Ten patients with bacterial overgrowth-related diarrhea underwent the following five 7-day treatment periods: untreated (control period), then placebo, and subsequently, in random order and blinded fashion, norfloxacin (800 mg/day), amoxicillin-clavulanic acid (1500 mg/day), and Saccharomyces boulardii (1500 mg/day). A hydrogen breath test was performed on the first and last day of each period. RESULTS: Daily stool frequency was similar during the control and placebo periods (4.2 +/- 0.6 vs. 3.9 +/- 0.6 [mean +/- SEM], respectively). Norfloxacin and amoxicillin-clavulanic acid led to a significant reduction in daily stool frequency (2.3 +/- 0.4 and 3.0 +/- 0.5, respectively; P < 0.01 vs. placebo period) after 2.0 +/- 1.4 and 1.2 +/- 0.4 days, which was maintained for 6.1 +/- 3.7 and 6.0 +/- 9.6 days, respectively. Breath-expired H(2) volume decreased with norfloxacin (37 +/- 8 to 12 +/- 5 mL per 2 hours; P < 0.01) and amoxicillin-clavulanic acid (24 +/- 6 to 8 +/- 4 mL per 2 hours, respectively; P = 0.01), but H(2) breath test result was negative in only 3 and 5 patients. CONCLUSIONS: Norfloxacin and amoxicillin-clavulanic acid are effective in the treatment of bacterial overgrowth-related diarrhea.

Adult↗
PubMed1985

[Treatment of Meniere disease with betahistine dimesilate (Aequamen)--double-blind study versus placebo (crossover)].

The efficacy of treatment of Menière's disease was investigated in 2 double blind study versus placebo. Forty patients were given 36 mg betahistine dimesilate daily for at least six weeks. The course of disease and findings one year before and one year after the treatment were noted and compared for assessing the therapeutic success. The findings on threshold audiograms, spontaneous and provoked nystagmus and caloric tests did not show any significant changes. A slight improvement was noted in the low frequency range of threshold audiograms. Dizziness, tinnitus and disturbances of walking were significantly improved. The incidence of vertigo attacks was reduced to 64%. In 89% of the patients no further vertigo attacks were seen after the treatment. The best results of betahistine dimesilate treatment were observed in the early stages of Menière's disease.

Adult↗
PubMed2003

The effect of dopamine type-2 receptor blockade on autonomic modulation.

Dopamine2 (D2)-like receptor antagonists are widely used for the treatment of gastroparesis and vomiting. Metoclopramide (MCP), a peripheral and central D2-like receptor antagonist, stimulates the sympathetic nervous system and may alter autonomic modulation, but the net effect of MCP to the heart is not known. The aim of our study was to investigate the effects of MCP on cardiac autonomic modulation, using power spectral analysis of heart rate variability. We evaluated the effect of MCP on cardiac autonomic modulation during prolonged supine and standing positions in 9 healthy men. We intravenously administered 10 mg MCP and placebo in a double blind and crossover manner to all participants during continuous electrocardiography recording. Placebo or MCP was administered after 15 minutes in supine position (REST phase), where participants remained for an additional 50 minutes (PSUP phase) and then stood up for 10 minutes (STA phase). Five-minute intervals were selected for power spectral analysis, and average values were calculated for low frequency (LF), normalized unit of LF (LFnu), high frequency (HF), normalized unit of HF (HFnu) components of the power spectrum, and for LF/HF ratio.Heart rate alterations were statistically significant during placebo administration (Friedman's p < 0.0001). These changes were related to the decrease in PSUP phase and increase in STA phase in post hoc analyses. There was a trend toward lower LFnu in PSUP phase (Friedman's p = 0.050), but LF/HF ratio changes did not reach a statistically significant level during placebo administration. MCP administration prevented the decrease in heart rate and LFnu component was seen with placebo in PSUP phase. Heart rate alterations also reached a significant level during MCP administration (Friedman's p = 0.002), and post hoc analyses showed that these changes were mainly related to the increase in STA phase. In contrast to placebo, MCP administration resulted in significant alterations in LFnu and LF/HF ratio (Friedman's p = 0.004 and p = 0.003, respectively). Two-way ANOVA model for LF/HF ratio changes showed that MCP induced a significant upward shift in LF/HF ratio than placebo during each phase of the study (F = 5.570; p = 0.031). We concluded that the net effect of MCP on sympathovagal balance is an increased sympathetic drive to the heart. MCP prevented the decrease in sympathetic drive to the heart during prolonged supine position and augmented sympathetic drive to the heart during mild sympathetic stimulation such as induced by standing up.

Adult↗
PubMed2004

Memetic algorithms for the unconstrained binary quadratic programming problem.

This paper presents a memetic algorithm, a highly effective evolutionary algorithm incorporating local search for solving the unconstrained binary quadratic programming problem (BQP). To justify the approach, a fitness landscape analysis is conducted experimentally for several instances of the BQP. The results of the analysis show that recombination-based variation operators are well suited for the evolutionary algorithms with local search. Therefore, the proposed approach includes--besides a highly effective randomized k-opt local search--a new variation operator that has been tailored specially for the application in the hybrid evolutionary framework. The operator is called innovative variation and is fundamentally different from traditional crossover operators, since new genetic material is included in the offspring which is not contained in one of the parents. The evolutionary heuristic is tested on 35 publicly available BQP instances, and it is shown experimentally that the algorithm is capable of finding best-known solutions to large BQPs in a short time and with a high frequency. In comparison to other approaches for the BQP, the approach appears to be much more effective, particularly for large instances of 1000 or 2500 binary variables.

Algorithms↗
PubMed1994

A comparative study of the effect of high-intensity transcutaneous nerve stimulation and oral naproxen on intrauterine pressure and menstrual pain in patients with primary dysmenorrhea.

OBJECTIVE: Our purpose was to compare the effects of high-intensity transcutaneous electrical nerve stimulation and oral naproxen (500 mg) on intrauterine pressure and menstrual pain. STUDY DESIGN: An open, randomized crossover study was performed on 12 women with primary dysmenorrhea. Intrauterine pressure was recorded with a microtransducer catheter, and the pain score was assessed by a visual analog scale. RESULTS: Before treatment all patients displayed signs of uterine hyperactivity as judged by a high resting pressure (7.5 +/- 0.4 kPa), high active pressure (24.0 +/- 0.8 kPa), and a high frequency of pressure cycles (13.3 +/- 0.5 contractions per 0.5 hour). Oral administration of naproxen suppressed (p < 0.01) all uterine activity parameters. Treatment with transcutaneous electrical nerve stimulation induced a prompt onset of pain relief in a strictly segmental manner, but there were no significant changes in uterine activity. The pain score was significantly reduced (p < 0.001) from 30 to 60 minutes after treatment with transcutaneous electrical nerve stimulation and from 19 to 120 minutes after naproxen administration. CONCLUSIONS: Treatment with transcutaneous electrical nerve stimulation induced a prompt onset of pain relief without any significant changes in uterine activity. Possible mechanisms for the pain relief, decreased uterine ischemia or decreased activity in the pain transmission system at spinal or supraspinal levels, are discussed.

Administration, Oral↗
PubMed1996

Percutaneous feeding tube changes in long-term-care facility patients.

OBJECTIVE: To compare patient outcomes when percutaneous feeding tubes were changed routinely each month or only when necessary (prn). DESIGN: Prospective, randomized, nonblinded crossover study of 6 months of routine monthly changes compared with 6 months of prn changes. SETTING: 416-bed long-term-care facility. PATIENTS: 26 permanent residents with nutrition managed through percutaneous gastrostomy or jejunostomy feeding tubes. The median age was 61.5 years; 8 (31%) also had tracheostomies, and 3 (12%) had indwelling urinary catheters. RESULTS: The frequency of feeding tube changes was 40 per 1,000 patient-days during the 6 months of routine tube changes and 14 per 1,000 when tubes were changed prn (P < .001). There were no differences between the two study periods in frequency of stoma site infections, fever, episodes of emesis, and total antibiotic courses. The median duration in situ of feeding tubes with prn changes was 104 days. For both periods, feeding tubes were significantly more likely to fall out and require replacement with-in 24 hours of previous tube replacement. CONCLUSION: There were no observed differences in clinical outcomes in long-term-care facility patients when feeding tubes were changed only as necessary as compared to routine monthly changes.

Adult↗
PubMed2004

Hysterectomy versus expanded medical treatment for abnormal uterine bleeding: clinical outcomes in the medicine or surgery trial.

OBJECTIVE: To compare clinical outcomes after randomization to hysterectomy versus medical treatment in patients with chronic abnormal uterine bleeding refractory to medroxyprogesterone acetate. METHODS: We randomly assigned 63 premenopausal women with abnormal uterine bleeding refractory to cyclic medroxyprogesterone acetate treatment to receive either a hysterectomy or expanded medical treatment. Within each randomized group, the specific treatment approach was determined by patient and provider preference. The primary analysis compared changes in clinical outcomes at 6 and 24 months by using an intention-to-treat approach. Secondary as-treated analyses after adjustment for baseline covariates compared participants randomly assigned to medical treatment who continued the medical approach with those who crossed over to hysterectomy. RESULTS: The intention-to-treat analyses at 6 months revealed greater symptom improvement in the hysterectomy group than in the medicine group for pelvic pain (P <.01), urinary urgency (P =.03), incomplete bladder emptying (P =.03), breast pain (P =.02), and cessation of vaginal bleeding (87% versus 11%, P <.001). Seventeen of 32 women assigned to medicine (53%) eventually crossed over and received a hysterectomy, and by 24 months the statistically significant differences by intention-to-treat were limited to greater improvement in hot flushes (P <.01) and cessation of vaginal bleeding (P <.01). Within-group analyses at year 2 showed statistically significant improvements from baseline on most symptoms for women who had a hysterectomy, whether through randomization or crossover. Women remaining on medical treatments had statistically significant improvements in pelvic pain, pelvic/bladder pressure, and stress incontinence. In a nonrandomized comparison with women who remained on medical treatments through year 2, those crossing over to hysterectomy experienced greater improvements in bleeding (P <.01), pelvic pain (P <.01), low back pain (P =.02), breast pain (P =.01), urinary frequency (P =.01), and urgency (P =.02). However, they also experienced more days off from work or usual activities (P <.01) and more days spent in bed (P <.01) than those who remained on medicine. CONCLUSION: For patients with abnormal uterine bleeding refractory to medroxyprogesterone acetate, hysterectomy is superior to expanded efforts with oral medications for alleviating clinical symptoms but may lead to more days of restricted activity.

Adult↗
PubMed2004

Genetic and physical mapping of homoeologous recombination points involving wheat chromosome 2B and rye chromosome 2R.

Wide hybrids have been used in generating genetic maps of many plant species. In this study, genetic and physical mapping was performed on ph1b-induced recombinants of rye chromosome 2R in wheat (Triticum aestivum L.). All recombinants were single breakpoint translocations. Recombination 2RS-2BS was absent from the terminal and the pericentric regions and was distributed randomly along an intercalary segment covering approximately 65% of the arm's length. Such a distribution probably resulted from structural differences at the telomeres of 2RS and wheat 2BS arm that disrupted telomeric initiation of pairing. Recombination 2RL-2BL was confined to the terminal 25% of the arm's length. A genetic map of homoeologous recombination 2R-2B was generated using relative recombination frequencies and aligned with maps of chromosomes 2B and 2R based on homologous recombination. The alignment of the short arms showed a shift of homoeologous recombination toward the centromere. On the long arms, the distribution of homoeologous recombination was the same as that of homologous recombination in the distal halves of the maps, but the absence of multiple crossovers in homoeologous recombination eliminated the proximal half of the map. The results confirm that homoeologous recombination in wheat is based on single exchanges per arm, indicate that the distribution of these single homoeologous exchanges is similar to the distribution of the first (distal) crossovers in homologues, and suggest that successive crossovers in an arm generate specific portions of genetic maps. A difference in the distribution of recombination between the short and long arms indicates that the distal crossover localization in wheat is not dictated by a restricted distribution of DNA sequences capable of recombination but by the pattern of pairing initiation, and that can be affected by structural differences. Restriction of homoeologous recombination to single crossovers in the distal part of the genetic map complicates chromosome engineering efforts targeting genes in the proximal map regions.

Chromosome Mapping↗
PubMed1993

A comparison of the ocular tolerability of a single dose of timolol and levobunolol in healthy normotensive volunteers.

Subject acceptance of a single dose of timolol and levobunolol was compared in a three-center, double-masked, randomized, crossover study in healthy normal subjects. We tested 115 subjects who received the medications OU, in a random order, separated by a washout period of three to seven days. At the end of the administration, the subjects were asked to report any symptoms and were monitored by ophthalmologic examination. Those receiving levobunolol reported a two- to threefold higher frequency of symptoms than did those receiving timolol (P = .0002, by Mainland-Gart chi-square test). Thirty-five subjects (30.4%) treated with levobunolol complained of burning versus 14 (12.2%) receiving timolol (P = .0021). Similar results were obtained in regard to stinging (31 versus 10 subjects; P = .0011). The duration of these symptoms did not differ between the two groups (P > .05). Timolol induced considerably less burning and stinging on day 1 compared with levobunolol, using a visual analog scale over time (P = .0004). Seventy-nine percent of those stating a preference chose timolol (P < 3 x 10(-9).

Adult↗
PubMed1996

Masturbation prohibition in sex offenders: a crossover study.

Some self-help groups for individuals with aberrant sexual interests (e.g., Sexaholics Anonymous and Sex and Love Addicts Anonymous) maintain that a period of "sexual sobriety" is necessary for treatment. The hypothesis was tested that sexual urges during a 30-day period of voluntary abstinence from masturbation would be less frequent and intense than during a period when masturbation was not avoided. Outpatient pedophiles were randomly assigned to either refrain from masturbating or make no attempt to alter their masturbation frequency for a period of 30 days. All participants were crossed over to the other treatment condition at the start of the 2nd month. Sexual urges and behavior were measured using weekly self-reports. A repeated measures ANOVA failed to show a difference in reported intensity of sexual urges, F(7, 91) = 1.15, p = 0.34; masturbation urges, F(7, 91) = 1.73, p = 0.11; adult sex urges, F(7, 91) = 1.82, p = 0.09; or child sex urges, F(7, 91) = 1.58, p = 0.15, in Masturbation Allowed vs. Masturbation Not Allowed conditions. Of 17 participants, 3 (18%) were able to retain completely from masturbating for 1 month, 4 participants (25%) thought it was helpful not to masturbate; 1 participant (7%) thought therapists should recommend avoidance of masturbation. This study suggests that sexual sobriety from masturbation does not aid in the control of pedophilic fantasies. This may be because the technique is ineffective, or because so few participants are willing to engage in it.

Adult↗
PubMed1987

Efficacy of diltiazem in variant angina. Results of a double-blind crossover study in CCU by Holter monitoring. The possible occurrence of a withdrawal syndrome.

The short and long term efficacy of diltiazem, a calcium-entry blocker, has been evaluated in a group of ten patients with Prinzmetal's variant angina admitted to a CCU. In the short term part of the study, after a run-in period, diltiazem 60 mg tid and placebo were administered alternatively during 4 randomized 72 hour periods. Response was assessed using continuous Holter monitoring, measuring the frequency of transient ischemic attacks. During the run-in period the number of episodes/day/patient was 16.1. No episodes of transient ST segment elevation were recorded during both periods of diltiazem treatment in 3 patients and during one of the two periods in 4. For the group as a whole the number of episodes during the first placebo period was not statistically different from that during the run-in period (208 versus 161). No statistically significant difference was also found in 8 patients comparing the number of episodes during the second placebo period and the run-in period (166 versus 101). During each period of diltiazem treatment an highly significant reduction in the number of episodes was observed (43 and 5, p = .006 and p = .02). Two patients did not complete the study protocol. Both patients had a worsening of angina during the first placebo period following diltiazem treatment. One of them developed an acute myocardial infarction. The possible occurrence of a rebound phenomenon after withdrawal of diltiazem seems to be indicated, in 6 patients, by a significant increase in the number of ischemic episodes recorded during the placebo period following active treatment in respect to the number during the first placebo period (159 versus 73, p = .04).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1996

Human immunodeficiency virus type 1 subtypes defined by env show high frequency of recombinant gag genes. The UNAIDS Network for HIV Isolation and Characterization.

Genetic subtypes of human immunodeficiency virus type 1 can be distinguished on the basis of phylogenetic analysis of their envelope (env) gene. A significant proportion of human immunodeficiency virus type 1 strains was retrospectively shown to result from recombination events between viruses belonging genetically to distinct subtypes (D. L. Robertson, P. M. Sharp, F. E. McCutchan, and B. H. Hahn, Nature [London] 374:124-126, 1995). To establish the frequency of natural infections with recombinant viruses and to exclude tissue culture artifacts, we analyzed plasma samples from the UNAIDS sample collection. The collection includes samples from 53 individuals infected with subtype A (n = 9), subtype B (n = 15), subtype C (n = 1), subtype D (n = 13), and subtype E (n = 15) on the basis of V3 region analysis. Phylogenetic analysis of the gag gene fragment showed intersubtype recombinant genomes in 23 cases: 3 of 9 (33%) of subtype A, 2 of 15 (13%) of subtype B, 3 of 13 (23%) of subtype D, and all of subtype E. Of the 23 recombinant viruses, 19 had a gag gene from one subtype and env from another (B(env)/C(gag), A(env)/C(gag), D(env)/A(gag), and E(env)/A(gag)). Phylogenetic analysis clustered the A(gag) of subtype E viruses as an outgroup of subtype A, suggesting that these viruses may belong to a distinct A' cluster. The remaining four recombinant viruses (B(env)/B(p17)F(p24), A(env)/A(p17)D(p24), A(env)/A(p17)C(p24), and D(env)/ D(p17)A(p24)) had breakpoint crossover sites in the proximity of the p17-p24 protein processing site. We conclude that recombination in the gag gene is highly frequent among the major env subtypes and that selection of recombinants is apparently based on particularly beneficial combinations of gag and env gene products.

Gene Frequency↗
PubMed1986

Comparison of nifedipine alone with propranolol alone for stable angina pectoris including hemodynamics at rest and during exercise.

The effects of nifedipine (60 to 90 mg/day) and propranolol (240 mg/day) on symptoms, angina threshold and cardiac function were compared in a placebo-controlled, double-blind, crossover study. Five-week treatment periods with nifedipine and propranolol were compared with 2 weeks of placebo treatment in 21 men with chronic stable angina pectoris, 13 of whom had symptoms both at rest and on exertion. Compared with placebo, New York Heart Association functional class improved in patients equally with nifedipine (p = 0.001) and propranolol (p = 0.006). Frequency of chest pain decreased with nifedipine (p = 0.001) and propranolol (p = 0.01), and nitroglycerin consumption similarly decreased with both treatments. Nifedipine significantly delayed the onset of chest pain (p = 0.01) and 1 mm of ST-segment depression (p = 0.002) during bicycle exercise; smaller increases with propranolol were not statistically significant. A preferential clinical response to nifedipine (9 patients) or propranolol (6 patients) was unrelated to the presence or absence of pain at rest or to any baseline hemodynamic finding. Nifedipine and propranolol were equally effective in relieving exertional ischemia as shown by improvements in ejection fraction at identical workloads, from 0.48 +/- 0.11 to 0.58 +/- 0.12 (p less than 0.001) and 0.56 +/- 0.14 (p less than 0.001), respectively. Exercise wall motion, assessed by a semiquantitative wall motion score, also improved with both drugs. Propranolol treatment decreased exercise cardiac output by 14% (p = 0.01) through its effect on heart rate. In contrast, nifedipine treatment had no effect on cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Effects of oral pirenzepine on heart rate variability and baroreceptor reflex sensitivity after acute myocardial infarction.

OBJECTIVES: Our aims were 1) to assess whether oral pirenzepine could increase indexes of cardiac vagal activity in postinfarction patients, and 2) to compare the effects of this agent with those of transdermal scopolamine. BACKGROUND: Depression of vagal tone and reflexes predicts a poor arrhythmic outcome after myocardial infarction. Interventions for shifting the sympathovagal balance toward vagal dominance are now of increased clinical interest. Intravenous pirenzepine increases RR interval variability in normal volunteers, a finding that could have therapeutic implications if confirmed in postinfarction patients after oral administration of the drug. METHODS: In a single-blind placebo-controlled crossover trial, short-term RR interval variability and baroreceptor reflex sensitivity were evaluated in 20 patients an average of 19 +/- 6 days after infarction. Analysis was performed during control conditions and during administration of placebo, oral pirenzepine and transdermal scopolamine. RESULTS: Compared with placebo, at a dose of 25 mg twice daily, pirenzepine significantly increased all time and frequency domain measures of RR interval variability and augmented baroreceptor reflex sensitivity by 60% (mean +/- 1 SD 10.4 +/- 5.9 vs. 6.5 +/- 3.2 ms/mm Hg, p = 0.0007). Pirenzepine and scopolamine showed a similar vagomimetic effect, but the overall incidence of adverse effects was lower with pirenzepine (1 [5%] of 20 vs. 10 [50%] of 20). CONCLUSIONS: In patients with a recent myocardial infarction, oral pirenzepine proved equal to transdermal scopolamine in significantly increasing indexes of cardiac vagal activity. These data suggest that oral pirenzepine may have a therapeutic potential for preventing malignant ventricular arrhythmias after infarction.

Administration, Cutaneous↗
PubMed2001

Dual-site atrial pacing for atrial fibrillation in patients without bradycardia.

Atrial pacing has been shown to delay the onset of atrial fibrillation (AF) when compared with ventricular pacing in patients with sick sinus syndrome. The role for pacing in the control of AF in patients without bradycardia is uncertain. We performed a randomized, crossover, single-blinded study in 22 patients (14 women, aged 63 +/- 10 years) with paroxysmal AF refractory to treatment with oral sotalol (202 +/- 68 mg/day) and no bradycardic indication for pacing. All patients received a dual-chamber pacemaker with 2 atrial pacing leads positioned at the high right atrium and coronary sinus ostium, respectively. Patients were randomized in a crossover fashion to be paced for 12 weeks, either with high right atrial (RA) pacing at 30 beats/min ("Off") or dual-site RA pacing with an overdrive algorithm that maintained atrial pacing at a rate slightly above the sinus rate ("On"). Treatment on resulted in a significantly higher percentage of atrial pacing and a reduction in atrial ectopic frequency than the treatment off period. The time to the first clinical AF recurrence was prolonged (15 +/- 17 to 50 +/- 35 days, p = 0.006), and total AF burden was reduced (45 +/- 34% vs 22 +/- 29%, p = 0.04) in the on-treatment phase. However, there was no difference in AF checklist symptom scores or overall quality-of-life measures. Dual-site RA pacing with continued sinus overdrive prolonged the time to AF recurrence and decreased AF burden in patients with paroxysmal AF. The absence of a major impact on symptom control suggests that pacing should be used as an adjunctive therapy with other treatment modalities for AF.

Adolescent↗
PubMed1983

A clinical pharmacological comparison of diclofensine (Ro 8-4650) with nomifensine and amitriptyline in normal human volunteers.

1 Ten healthy male volunteers participated in a double-blind placebo-controlled crossover comparison of the pharmacodynamic profiles of single oral doses of diclofensine 25 mg and 50 mg, nomifensine 75 mg and amitriptyline 50 mg. 2 Diclofensine did not influence salivary flow or consistently affect pupil diameter and had no significant effect on subjective measurements of sedation and mood. It had no effect on reaction time, or on critical flicker frequency. 3 By contrast, amitriptyline significantly reduced salivary flow, produced significant sedation and impairment of mood, prolonged reaction time, and appeared to decrease (but not significantly) critical flicker frequency. 4 Nomifensine significantly reduced (i.e. improved) reaction time, and inhibited salivary flow. 5 Diclofensine did not significantly influence heart rate, blood pressure, systolic time intervals or high speed electrocardiogram. 6 No significant treatment-related differences were observed in serum prolactin, cortisol or growth hormone levels.

Adolescent↗