Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “crossover frequency”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,117 records · Page 62Linked to original sources
PubMed1987

[Betablocker vs placebo in vasomotor headache. A double-blind crossover study].

Vasomotor headaches are commonly, especially in the international literature, classified under ordinary migraine. Since beta-blockers seem to be the drug of choice in the prevention of migraine, 30 patients were given placebo and three times 40 mg propranolol in a double-blind cross-over trial. Among 24 fully assessable sets of tests only four showed a decrease in the frequency of headaches by more than 50%. In three patients the frequency actually increased over the placebo effect.

Adrenergic beta-Antagonists↗
PubMed2001

Nutritional supplements used in weight-reduction programs increase intestinal gas in persons who malabsorb lactose.

OBJECTIVE: To determine if ingestion of 2 doses of milk-based dietary supplements produce gaseous symptoms in subjects who malabsorb lactose. DESIGN: Randomized, controlled, crossover trial. SUBJECTS/SETTING: Ten community-based subjects who malabsorb lactose. INTERVENTION: Ingestion of 2 standard servings of milk-based supplements (a powder reconstituted in fat-free milk or a ready-to-drink preparation) or low-lactose control preparations. MAIN OUTCOME MEASURES: Frequency of flatus passage and subjective impression of bloating, flatulence, and abdominal discomfort. STATISTICAL ANALYSIS: Wilcoxon signed-rank test. RESULTS: The high lactose content (27 g) of 2 servings of the powder-based supplement ingested without other food resulted in a marked increase in daily flatus passages from the basal level of 9.7+/-8.2 to 30+/-14 (mean+/-SD), and a significant increase in the subjects' perception of gas. In contrast, the lower lactose content (18.4 g) of 2 servings of a ready-to-drink supplement resulted in a flatus frequency of 17+/-10 (P=.14 vs baseline) and no significant increase in the perception of increased gas. Neither supplement resulted in a significant increase in bloating, abdominal pain, or diarrhea. The lactose content of the liquid supplement was reduced by 80% following overnight incubation with an over-the-counter lactase preparation. APPLICATIONS/CONCLUSIONS: Persons who malabsorb lactose should be aware that sizable increases in rectal gas commonly occur when milk-based powders reconstituted in milk are used as meal replacements. In contrast, gas problems probably will be minor following ingestion of 2 doses of a ready-to-drink, milk-based supplement. The lactose content of these supplements can be markedly reduced by overnight incubation with over-the-counter lactase preparations, and this manipulation should be beneficial for subjects troubled by the increased gas caused by the consumption of lactose-containing supplements.

Abdominal Pain↗
PubMed2001

Treatment of Severe Intradialytic Hypotension With the Addition of High Dialysate Calcium Concentration to Midodrine and/or Cool Dialysate.

Treatment of intradialytic hypotension (IDH) in the end-stage renal disease population has been a difficult task for nephrologists caring for these patients. The presence of multiple pathogenic factors contributes to hemodynamic instability and explains why therapies that modulate only a specific aspect of the problem are only partially effective. Cool dialysate (34.5 degrees C to 35.5 degrees C) and midodrine may provide hemodynamic stability through an increase in peripheral vascular resistance, whereas high dialysate calcium concentration (HDCa; 3.5 mEq/L) improves intradialytic blood pressure through preservation of cardiac output. Theoretically, the combination of these two types of therapies might further reduce the frequency and severity of hypotension during hemodialysis (HD). We undertook a study to evaluate the effect of HDCa added to midodrine and/or cool dialysate in the treatment of patients with severe IDH. Twenty-eight patients met the entry criteria, and 23 patients completed the prospective crossover study. Five patients dropped out of the study secondary to hypercalcemia. The addition of HDCa significantly improved post-HD mean arterial pressure (MAP; 95.6 +/- 12.7 versus 90.8 +/- 12.5 mm Hg; P = 0.002). The decreases in MAP from pre-HD to lowest intradialytic (16.3 +/- 8.2 versus 20.6 +/- 10.0 mm Hg; P = 0.009) and pre-HD to post-HD (2.0 +/- 8.5 versus 8.15 +/- 10.8 mm Hg; P = 0.002) were significantly reduced with HDCa compared with low dialysate calcium. However, there were no significant improvements in symptoms of or interventions for IDH. Thus, it appears that the addition of HDCa to midodrine and/or cool dialysate further improves blood pressure in patients with IDH. However, this therapy did not reduce symptoms or interventions required for IDH. In addition, hypercalcemia complicated this therapy in 22% of the patients.

Blood Pressure↗
PubMed1988

Genetic analysis of mouse t haplotypes using mutations induced by ethylnitrosourea mutagenesis: the order of T and qk is inverted in t mutants.

The t region of mouse chromosome 17 exhibits recombination suppression with wild-type chromatin. However, the region has resisted classical genetic dissection because of a lack of defined variants. Mutations induced by N-ethyl-N-nitrosourea (ENU) at the Brachyury (T), quaking (qk), and tufted (tf) loci of the mouse tw5 haplotype have now allowed the analysis of crossovers between two complete t haplotypes. A classical breeding analysis of the complete t haplotypes, tw5 and t12, utilizing the newly induced markers, reveals two inversions in t chromatin: one involving T and qk, and one involving tf and the H-2 complex. Moreover, the recombination frequency between the loci of T and qk is reduced compared to the frequency reported in normal chromatin. These two inversions are a sufficient explanation for the recombination inhibition with normal chromatin exhibited by t haplotypes isolated from the wild. Furthermore, the reduced recombination frequency between T and qk may indicate that the proximal gene rearrangement is not a simple inversion.

Animals↗
PubMed1998

Long, interrupted conversion tracts initiated by cog in Neurospora crassa.

Multiple polymorphisms distinguish Emerson and Lindegren strains of Neurospora crassa within the histidine-3 gene and in its distal flank. Restriction site and sequence length polymorphism in a set of 14 PCR products covering this 6.9-kb region were used to identify the parental origin of DNA sequence information in prototrophic progeny of crosses heterozygous for auxotrophic mutations in his-3 and the silent sequence differences. Forty-one percent of conversion tracts are interrupted. Where the absence of rec-2+ permits activity of the recombination hotspot cog, conversion appears to originate at cog and conversion tracts are up to 5.9 kb long. The chromosome bearing cog(L), the dominant allele that confers a high frequency of recombination, is almost invariably the recipient of information. In progeny from crosses heterozygous rec-2/rec-2+, conversion tracts are much shorter, most are not initiated at cog and either chromosome seems equally likely to be converted. Although 32% of his-3 prototrophs have a crossover that may be associated with conversion, it is suggested that the apparent association between conversion and crossing over at this locus may be due to confounding of coincidental events rather than to a mechanistic relationship.

Alleles↗
PubMed2004

Scaling and crossovers in activated escape near a bifurcation point.

Near a bifurcation point a system experiences a critical slowdown. This leads to scaling behavior of fluctuations. We find that a periodically driven system may display three scaling regimes and scaling crossovers near a saddle-node bifurcation where a metastable state disappears. The rate of activated escape W scales with the driving field amplitude A as ln W proportional, variant ( A(c) -A)(xi), where A(c) is the bifurcational value of A. With increasing field frequency the critical exponent xi changes from xi=3/2 for stationary systems to a dynamical value xi=2 and then again to xi=3/2. The analytical results are in agreement with the results of asymptotic calculations in the scaling region. Numerical calculations and simulations for a model system support the theory.

Journal Article↗
PubMed2006

Flux through a hole from a shaken granular medium.

We have measured the flux of grains from a hole in the bottom of a shaken container of grains. We find that the peak velocity of the vibration, v max, controls the flux, i.e., the flux is nearly independent of the frequency and acceleration amplitude for a given value of v max. The flux decreases with increasing peak velocity and then becomes almost constant for the largest values of v max. The data at low peak velocity can be quantitatively described by a simple model, but the crossover to nearly constant flux at larger peak velocity suggests a regime in which the granular density near the container bottom is independent of the energy input to the system.

Journal Article↗
PubMed1989

Meta-analysis of European placebo controlled studies of vigabatrin in drug resistant epilepsy.

1. A meta-analysis has been performed on nine placebo controlled trials of vigabatrin (GVG) administered as add-on therapy to patients suffering from drug resistant epilepsy. 2. There were two pilot placebo-controlled dose ranging studies, six double-blind crossover studies and a multicentre response controlled study. 3. There were a total of 398 patients entered and 390 have been evaluated for safety and 337 for efficacy. 4. In spite of the difficulties in the clinical evaluation of new antiepileptic drug, a reduction in seizure frequency was reported following the addition of vigabatrin to the concomitant medication in all studies. This was statistically significant in the larger of the two pilot studies, the multicentre study and three of the six double-blind studies. 5. There was a statistically significant reduction in seizures of in all six double-blind studies when the 98 patients suffering from complex partial seizures with or without generalisation were considered. Seventy two percent of these patients showed a greater than 25% reduction in seizure frequency. 6. Vigabatrin was well tolerated. The frequency of adverse events was similar to that reported elsewhere.

Aminocaproates↗
PubMed2003

Nitric oxide regulates retinal vascular tone in humans.

The purpose of the present study was to investigate the contribution of basal nitric oxide (NO) on retinal vascular tone in humans. In addition, we set out to elucidate the role of NO in flicker-induced retinal vasodilation in humans. Twelve healthy young subjects were studied in a three-way crossover design. Subjects received an intravenous infusion of either placebo or NG-monomethyl-L-arginine (L-NMMA; 3 or 6 mg/kg over 5 min), an inhibitor of NO synthase. Thereafter, diffuse luminance flicker was consecutively performed for 16, 32, and 64 s at a frequency of 8 Hz. The effect of L-NMMA on retinal arterial and venous diameter was assessed under resting conditions and during the hyperemic flicker response. Retinal vessel diameter was measured with a Zeiss retinal vessel analyzer. L-NMMA significantly reduced arterial diameter (3 mg/kg: -2%; 6 mg/kg: -4%, P < 0.001) and venous diameter (3 mg/kg: -5%; 6 mg/kg: -8%, P < 0.001). After placebo infusion, flicker induced a significant increase in retinal vessel diameter (P < 0.001). At a flicker duration of 64 s, arterial diameter increased by 4% and venous diameter increased by 3%. L-NMMA did not abolish these hyperemic responses but blunted venous vasodilation (P = 0.017) and arterial vasodilation (P = 0.02) in response to flicker stimulation. Our data indicate that NO contributes to basal retinal vascular tone in humans. In addition, NO appears to play a role in flicker-induced vasodilation of the human retinal vasculature.

Adult↗
PubMed1988

Diltiazem, nifedipine, and their combination in patients with stable angina pectoris: effects on angina, exercise tolerance, and the ambulatory electrocardiographic ST segment.

The efficacy and safety of oral nifedipine and diltiazem were compared in 20 patients with stable angina pectoris with use of a placebo run-in, randomized, double-blind titration to maximal effect crossover protocol. The effects of treatment withdrawal were also analyzed. All patients received placebo for 2 weeks and were then randomly assigned to receive either diltiazem or nifedipine. A 2 week drug titration phase in which patients received either diltiazem (180 to 360 mg/day) or nifedipine (30 to 120 mg/day) in three divided doses was followed by a 1 week maintenance phase. Patients then received placebo for 1 to 2 weeks, followed by crossover to the other treatment regimen and a second placebo washout period of 1 week. Patients (n = 13) who remained symptomatic on both diltiazem and nifedipine during the monotherapy periods entered a 3 week combination treatment phase, followed by a final 1 week placebo washout period. Frequency of angina, nitroglycerin consumption, exercise tolerance (Naughton protocol), and frequency of daily episodes of ST segment deviations on the electrocardiogram (1 mm of ST segment depression persisting for at least 1 min with and without chest pain) on an ambulatory electrocardiographic monitor were assessed during the baseline placebo, active monotherapy, placebo withdrawal, and combination treatment phases. Plasma drug levels were also measured. Compared with initial placebo values, the frequency of angina and the amount of nitroglycerin treatment were reduced by both diltiazem (p less than .001) and nifedipine (p less than .02). Diltiazem was more effective than nifedipine in reducing angina (p less than .02). Exercise duration increased with both drugs (p less than .0001). Diltiazem was significantly better than nifedipine in reducing the episodes of ST segment depression on the ambulatory monitor (p less than .01). Diltiazem reduced the resting heart rate (p less than .01); both drugs reduced the resting blood pressure and rate-pressure product. Overall, combination therapy was more effective in patients who did not maximally respond to diltiazem or nifedipine alone with respect to anginal and exercise variables and in reducing blood pressure at rest and during exercise. Plasma drug levels could not predict an individual patient's treatment response. Diltiazem may increase nifedipine drug levels when the drugs are combined. Fewer side effects were observed with diltiazem than nifedipine; the most side effects were seen with combination treatment. There were no apparent withdrawal effects observed with either treatment regimen.(ABSTRACT TRUNCATED AT 400 WORDS)

Angina Pectoris↗
PubMed2003

Comparative impact of guidelines, clinical data, and decision support on prescribing decisions: an interactive web experiment with simulated cases.

OBJECTIVE: The aim of this study was to compare the clinical impact of computerized decision support with and without electronic access to clinical guidelines and laboratory data on antibiotic prescribing decisions. DESIGN: A crossover trial was conducted of four levels of computerized decision support-no support, antibiotic guidelines, laboratory reports, and laboratory reports plus a decision support system (DSS), randomly allocated to eight simulated clinical cases accessed by the Web. MEASUREMENTS: Rate of intervention adoption was measured by frequency of accessing information support, cost of use was measured by time taken to complete each case, and effectiveness of decision was measured by correctness of and self-reported confidence in individual prescribing decisions. Clinical impact score was measured by adoption rate and decision effectiveness. RESULTS: Thirty-one intensive care and infectious disease specialist physicians (ICPs and IDPs) participated in the study. Ventilator-associated pneumonia treatment guidelines were used in 24 (39%) of the 62 case scenarios for which they were available, microbiology reports in 36 (58%), and the DSS in 37 (60%). The use of all forms of information support did not affect clinicians' confidence in their decisions. Their use of the DSS plus microbiology report improved the agreement of decisions with those of an expert panel from 65% to 97% (p=0.0002), or to 67% (p=0.002) when antibiotic guidelines only were accessed. Significantly fewer IDPs than ICPs accessed information support in making treatment decisions. On average, it took 245 seconds to make a decision using the DSS compared with 113 seconds for unaided prescribing (p<0.001). The DSS plus microbiology reports had the highest clinical impact score (0.58), greater than that of electronic guidelines (0.26) and electronic laboratory reports (0.45). CONCLUSION: When used, computer-based decision support significantly improved decision quality. In measuring the impact of decision support systems, both their effectiveness in improving decisions and their likely rate of adoption in the clinical environment need to be considered. Clinicians chose to use antibiotic guidelines for one third and microbiology reports or the DSS for about two thirds of cases when they were available to assist their prescribing decisions.

Anti-Bacterial Agents↗
PubMed1994

[Adolescents' reasons for visiting a doctor].

OBJECTIVE: To discover what use adolescents make of the medical services in a Health Area and why they attend. DESIGN: A descriptive epidemiological study of a crossover type. SETTING: Santa Maria de Benquerencia Health Centre, Toledo. PATIENTS AND OTHER PARTICIPANTS: Between July 1992 and June 1993, 717 clinical records selected by means of systematic sampling out of 2127 records of 14 to 18 year old adolescents were examined. MEASUREMENTS AND MAIN RESULTS: Frequency of attendance was 2.15 per adolescent per year, with a standard error of 0.096. Significantly less males than females attended (p < 0.05). 66.53% attended at least once a year. The CIPSAP-2 groups most commonly found were: Respiratory System diseases (433 attendances), Supplementary Classification (231) and Dermatological diseases (177). We found a significantly higher attendance (p < 0.05) in males in the groups for Endocrino-metabolic illnesses and injuries/side-effects, and in females (p < 0.05) in illnesses of the Locomotive System. The commonest individual reasons for attendance were: Respiratory Infection of the upper passages, Prescriptions/Forms/Letters, Tonsillitis and Acne. CONCLUSIONS: Adolescents use the health services less than the rest of the population. Out of the pathologies giving rise to their attendance, the problems arising from the physiological changes and physical activity inherent to this age-group have great specific weight. However such important problems as those arising from so-called "life-style risks" do not appear to be common causes of adolescents seeking health care. We conclude with the need to devote greater and better Primary Health Care to this age-group in order to tackle this situation.

Adolescent↗
PubMed1993

Location of crossovers during gene targeting with insertion and replacement vectors.

Gene targeting was used to introduce nonselectable genetic changes into chromosomal loci in mouse embryo-derived stem cells. The nonselectable markers were linked to a selectable marker in both insertion- and replacement-type vectors, and the transfer of the two elements to the Hprt locus was assayed. When insertion vectors were used as substrates, the frequency of transfer was highly dependent upon the distance between the nonselectable marker and the double-strand break in the vector. A marker located close to the vector ends was frequently lost, suggesting that a double-strand gap repair activity is involved in vector integration. When replacement vectors were used, cotransfer of a selectable marker and a nonselectable marker 3 kb apart was over 50%, suggesting that recombination between vector and target often occurs near the ends of the vector. To illustrate the use of replacement vectors to transfer specific mutations to the genome, we describe targeting of the delta F508 mutation to the CFTR gene in mouse embryo-derived stem cells.

Animals↗
PubMed2000

Studies of interaural attenuation to investigate the validity of a dichotic difference tone response recorded from the inferior colliculus in the chinchilla.

In a previous paper (Arnold and Burkard, 1998) a dichotic f2-f1 difference tone (DT) auditory evoked potential from the chinchilla inferior colliculus (IC) was measured while presenting f1 (2000 Hz) to one ear and f2 (2100 Hz) to the other ear. This measurement paradigm could be used as a means to study binaural processing in an unanesthetized animal model. However, it is possible that this response is actually generated peripherally, as a result of acoustic crossover. The purpose of the present set of experiments was to investigate whether the dichotic DT is a true binaural phenomenon. Recordings were made from chronically implanted IC electrodes in unanesthetized, monaural chinchillas (left cochlea destroyed). In experiment 1, interaural attenuation (IA) was measured in two ways. First, IA was measured by comparing IC evoked potential thresholds obtained when stimulating the normal right ear and the dead left ear, using tone bursts (0.5-8 kHz). Mean values of interaural attenuation ranged from 50-65 dB across frequency (55 dB at 2000 Hz). Next, the DT was measured monaurally using f1 = 2000 and f2 = 2100 (L1 = L2). By comparing the mean DT input/output functions for monaural stimulation of the right and left ears, a mean value of IA for the tonal pair was estimated (approximately 69 dB). In experiment 2, the DT was measured with right monaural stimulation, while varying the relative levels of the primaries. A small DT could be seen with primary levels up to 30 dB apart, but not for greater level differences. Differences substantially greater than 30 dB would be expected in the crossover situation based upon IA. In experiment 3, the stimuli were presented dichotically (f1 to right ear, f2 to left ear and vice versa, L1 = L2) to determine whether acoustic crosstalk to the normal right ear would generate a DT. No DT was reliably observed in this condition. Taken together, these results suggest that the dichotic DT is a true binaural phenomenon, and not simply attributable to acoustic crossover.

Animals↗
PubMed1999

The Pacing Therapies for Congestive Heart Failure (PATH-CHF) study: rationale, design, and endpoints of a prospective randomized multicenter study.

In conjunction with pharmacologic therapy, pacing has been proposed as a potential treatment to decrease symptoms in patients with moderate-to-severe congestive heart failure (CHF). Uncontrolled studies of pacing therapy for CHF dealing with different pacing sites, modes of pacing, and atrioventricular delays have reported mixed outcomes. The Pacing Therapies in Congestive Heart Failure (PATH-CHF) study is a single-blind, randomized, crossover, controlled trial designed to evaluate the effects of pacing on acute hemodynamic function and to assess chronic clinical benefit in patients with moderate-to-severe CHF. The effect of pacing on oxygen consumption at peak exercise and at anaerobic threshold during cardiopulmonary exercise tests, and on 6-minute walk distance, have been selected as primary endpoints of the study. Secondary endpoints of the trial were changes in New York Heart Association (NYHA) functional class, quality-of-life as assessed by the Minnesota Living with Heart Failure questionnaire, and hospitalization frequency. Finally, changes in ejection fraction, cardiac output, and filling pattern were assessed by echocardiography. The trial was planned to include 53 patients from 7 centers in Europe over a period of 3 years. The study was divided into 2 parts: acute testing and chronic follow-up. The acute study, performed during the pacemaker implantation, involved extensive testing using a custom-designed computer (FLEXSTIM) and a unique burst pacing protocol (FLEXSTIM protocol) to determine the best ventricular pacing sites and the most appropriate atrioventricular delays. The chronic phase consisted of a crossover study designed to test in each patient the best univentricular pacing site and biventricular pacing as assessed by the acute hemodynamic study. The study started with the first implant in 1995 and has, to date, included 42 patients. The study is expected to be completed by the end of 1998. The results of a first interim analysis showed trends toward improvement in all primary and secondary endpoints during the pacing periods compared with no pacing.

Adult↗
PubMed2004

Caffeine attenuates waking and sleep electroencephalographic markers of sleep homeostasis in humans.

Prolonged wakefulness increases electroencephalogram (EEG) low-frequency activity (< 10 Hz) in waking and sleep, and reduces spindle frequency activity (approximately 12-16 Hz) in non-rapid-eye-movement (nonREM) sleep. These physiologic markers of enhanced sleep propensity reflect a sleep-wake-dependent process referred to as sleep homeostasis. We hypothesized that caffeine, an adenosine receptor antagonist, reduces the increase of sleep propensity during waking. To test this hypothesis, we compared the effects of caffeine and placebo on EEG power spectra during and after 40 h of wakefulness. A total of 12 young men underwent two periods of sleep deprivation. According to a randomized, double-blind, crossover design, they received two doses of caffeine (200 mg) or placebo after 11 and 23 h of wakefulness. Sleep propensity was estimated at 3-h intervals by measuring subjective sleepiness and EEG theta (5-8 Hz) activity, and polysomnographic recordings of baseline and recovery nights. Saliva caffeine concentration decreased from 15.7 micromol/l 16 h before the recovery night, to 1.8 micromol/l 1 h before the recovery night. Compared with placebo, caffeine reduced sleepiness and theta activity during wakefulness. Compared with sleep under baseline conditions, sleep deprivation increased 0.75-8.0 Hz activity and reduced spindle frequency activity in nonREM sleep of the recovery nights. Although caffeine approached undetectable saliva concentrations before recovery sleep, it significantly reduced EEG power in the 0.75-2.0 Hz band and enhanced power in the 11.25-20.0 Hz range relative to placebo. These findings suggest that caffeine attenuated the build-up of sleep propensity associated with wakefulness, and support an important role of adenosine and adenosine receptors in the homeostatic regulation of sleep.

Adult↗
PubMed1994

An efficient method for gene disruption in Neurospora crassa.

The frequency with which transforming DNA undergoes homologous recombination at a chromosomal site can be quite low in some fungal systems. In such cases, strategies for gene disruption or gene replacement must either select against ectopic integration events or provide easy screening to identify homologous site, double-crossover insertion events. A protocol is presented for efficient isolation of Neurospora crassa strains carrying a definitive null allele in a target gene. The protocol relies on the presence of a selectable marker flanking a disrupted plasmid-borne copy of the gene, and in the case presented led to a seven-fold enrichment for putative homologous site replacement events. In addition, a polymerase chain reaction assay is utilized for rapid identification of homologous recombinants among the remaining candidates. This protocol was used to identify 3 isolates, out of 129 primary transformants, which have a disruption in the Neurospora ccg-1 gene. The method should be applicable to a variety of fungal systems in which two selectable markers can be expressed, including those in which homologous recombination rates are too low to allow easy identification of homologous site insertions by the more traditional molecular method of Southern analysis. In addition to disrupting target genes for the purpose of generating null mutations, this method is useful for the targeting of reporter gene fusions to a native chromosomal site for the purpose of studying gene regulation.

Base Sequence↗
PubMed1989

Effects of dosing intervals on the development of tolerance to high dose transdermal nitroglycerin.

To investigate the antiischemic efficacy and development of tolerance to transdermal nitroglycerin, 14 patients with chronic, stable angina pectoris were studied using continuous ambulatory electrocardiographic monitoring. Patients demonstrated initial hemodynamic responsiveness to sublingual nitroglycerin and were titrated to a maximally tolerated dose of 30 to 60 mg/24 hours (52 +/- 5 mg). Two crossover phases were use in a randomized, double-blind, placebo-controlled manner: continuous nitroglycerin therapy (patches containing active drug worn for 24 hours) and intermittent nitroglycerin therapy (12-hour active drug followed by a 12-hour nitrate-free period). There were no differences in frequency or duration of ischemic episodes between the placebo days of each phase. A significant effect in frequency of episodes was observed between placebo and treatment days of continuous therapy (p less than 0.05). Nonsignificant reductions in frequency and duration of ischemic episodes also occurred during intermittent therapy. The major antiischemic effect of transdermal nitroglycerin therapy occurred during the first day of treatment but was lost by 48 hours. Reductions in frequency and duration of ischemic episodes (p less than 0.05) were present on day 1 of continuous therapy but ischemic episodes returned to placebo levels by day 2, suggesting the development of tolerance. Intermittent therapy did not prevent the development of tolerance on day 2 of treatment. The results demonstrate that the use of high doses of transdermal nitroglycerin in patients with chronic, stable coronary artery disease produced a beneficial reduction in the frequency and duration of ischemia. However, the antiischemic benefit was lost between 24 nd 48 hours after the onset of continuous and intermittent therapy, presumably due to tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗