Psychoneuroimmunology and health psychology: inflammation and protective factors.

A common clinical observation is the adverse relationship between stress and human diseases. The attention of scientific research on health has been disproportionately focused on risk factors that predict the onset of certain health outcomes, in particular there has been an increasing interest in the role of inflammation as a common mechanism of disease in a number of medical and neuropsychiatric diseases. Despite the importance of such research being undisputed, it is necessary to emphasize what the protective factors are that promote psychosocial recovery processes and increased survival rates in a biopsychosocial perspective. This article aims to understand the relationship between psychosocial factors and immune system in the interests of health psychology, highlighting the protective factors that promote recovery, resiliency and resistance to disease.

Cycling induced by functional electrical stimulation in children affected by cerebral palsy: case report.

BACKGROUND: Recently, the efficacy of functional electrical stimulation (FES) cycling have been demonstrated on the improvement of strength and motor control in adults with stroke. FES-cycling, providing a repetitive goal-oriented task, could facilitate cortical reorganization and utilization of residual cortico-spinal pathways. These benefits could be more enhanced in children because of the greater plasticity and flexibility of their central nervous system. AIM: The aim of the present case report study was to explore the feasibility of FES-cycling in children with cerebral palsy (CP) and to provide a set of instrumental measures able to evaluate the effects of this novel treatment on cycling and walking ability. DESIGN: Interventional study. SETTING AND POPULATION: Two ambulant outpatient children with diplegic CP were recruited by the "E. Medea" Scientific Institute. METHODS: Patients followed a FES-cycling treatment for 30 minutes a day, 3 days a week for 7 weeks. Pre and post treatment tests were performed, namely clinical measures and electromyographic, kinematic and oxygen expenditure analysis during gait and cycling. RESULTS: The treatment was safe, feasible and well accepted by the 2 children. After treatment both patients achieved a more symmetrical muscular strategy during voluntary cycling and gait and a significant reduction of muscle co-contractions during cycling. These improvements were corroborated by a decrease in oxygen expenditure during the post test for one of the two children, the less impaired, implying a better exploiting of bi-articular muscles. CONCLUSION AND CLINICAL REHABILITATION IMPACT: FES-cycling is feasible and safe and it may be an alternative rehabilitation method for diplegic CP patients. The set of instrumental measurements proposed seems to be a valuable tool for functional assessment to identify subclinical anomalies and improvements on cycling and gait in CP patients.

Comparación de la eficacia de la fototerapia convencional con tubos de luz azul vs. LEDs / Comparison of the efficacy of conventional phototherapy with blue light tubes vs LEDs

Introducción: La hiperbilirrubinemia (HB) es la principal causa de ingreso en unidades neonatales de bajo riesgo. Nuevos dispositivos de fototerapia (FT) permiten el uso de irradiación a dosis alta. Objetivo: Comparar la eficacia de la FT aplicada con equipos de tubos de luz azul (30 AW/cm2/nm) y FT con tecnología LEDÆs a dos niveles de irradiancia (30 y 40 AW/ cm2/nm) en términos de duración del tratamiento. Material y métodos: Estudio prospectivo, controlado y randomizado. Los recién nacidos de término o cercanos al término que necesitaban tratamiento con luminoterapia fueron aleatorizados a tres grupos: 1) luz azul a 30 AW/cm2/nm (LC), 2) LED a 30 AW/cm2/nm (L30), y 3) LED a 40 AW/cm2/nm (L40). Resultados: Se incluyeron 165 pacientes, 54 en LC, 56 en L30 y 55 en el grupo L40. El peso al nacer, edad gestacional, horas a la aleatorización y los valores BST al ingreso a FT (18,9 ± 2 mg/dl en BL, 18,9 ± 2,2 en L30 y 19 ± 1,6 en L40) fueron similares. El tiempo total (horas) de FT fue: 54,4 ± 6,9 en LC, 53,4 ± 10,7 en L30 y 41,7 ± 6 en L40 (p <0,001). Los niveles de BST en la interrupción de FT (10,1 ± 1,7 mg/dl, 9,9 ± 1 y 8,9 ± 1,8, p = 0,002) y 24 horas después (9,6 ± 1,3 mg/dl, 9,8 ± 1,4 y 9 ± 1,8, p = 0,04) fueron menor en el grupo L40. Conclusiones: El tratamiento con LEDs a 40 AW/cm2/nm reduce en 12 horas la duración del tratamiento en comparación con LEDs o luz azul a 30 AW/cm2/nm. (AU)

Introduction: Hyperbilirubinemia (HB) is the main cause of admission to low risk neonatal units. New phototherapy devices (PT) allow the use of high dose of irradiance. Objective: To compare the efficacy of PT in terms of hours of treatment between blue light tubes and LEDs equipments with two levels of irradiance. Material and methods: Prospective controlled trial. Term or near-term infants with need of PT treatment according to AAP recommendations were randomized into three groups: blue lights PT with 30 AW/cm2/nm (BL) or LEDs PT with 30 AW/cm2/nm (L30) or 40 AW/cm2/nm (L40) at skin level. Results: 165 patients were included, 54 in the BL group, 56 in L30 and 55 in L40 group. Birth weight, gestational age, postnatal hours at randomization and total serum bilirubin (TSB) level at entry (18.9 ± 2 mg/dl in BL, 18.9 ± 2.2 in L30 and 19 ± 1.6 in L40) were similar between groups. Total time of PT were 54.4 ± 6.9 hours in BL, 53.4 ± 10.7 in L30 and 41.7 ± 6 in L40 (p <0.001). TSB levels at PT discontinuation (10.1 ± 1.7 mg/dl, 9.9 ± 1 and 8.9 ± 1.8, p = 0.002) and 24 hours later (9.6 ± 1.3 mg/dl, 9.8 ± 1.4 and 9 ± 1.8, p = 0.04) were lower in L40 group.Conclusions: PT treatment with LEDs at AW/cm2/nm reduced the duration of treatment in 12 hours compared with BL or LEDs at 30 AW/cm2/nm. (AU)

Comparación de la eficacia de la fototerapia convencional con tubos de luz azul vs. LEDs / Comparison of the efficacy of conventional phototherapy with blue light tubes vs LEDs

Introducción: La hiperbilirrubinemia (HB) es la principal causa de ingreso en unidades neonatales de bajo riesgo. Nuevos dispositivos de fototerapia (FT) permiten el uso de irradiación a dosis alta. Objetivo: Comparar la eficacia de la FT aplicada con equipos de tubos de luz azul (30 µW/cm2/nm) y FT con tecnología LED’s a dos niveles de irradiancia (30 y 40 µW/ cm2/nm) en términos de duración del tratamiento. Material y métodos: Estudio prospectivo, controlado y randomizado. Los recién nacidos de término o cercanos al término que necesitaban tratamiento con luminoterapia fueron aleatorizados a tres grupos: 1) luz azul a 30 µW/cm2/nm (LC), 2) LED a 30 µW/cm2/nm (L30), y 3) LED a 40 µW/cm2/nm (L40). Resultados: Se incluyeron 165 pacientes, 54 en LC, 56 en L30 y 55 en el grupo L40. El peso al nacer, edad gestacional, horas a la aleatorización y los valores BST al ingreso a FT (18,9 ± 2 mg/dl en BL, 18,9 ± 2,2 en L30 y 19 ± 1,6 en L40) fueron similares. El tiempo total (horas) de FT fue: 54,4 ± 6,9 en LC, 53,4 ± 10,7 en L30 y 41,7 ± 6 en L40 (p <0,001). Los niveles de BST en la interrupción de FT (10,1 ± 1,7 mg/dl, 9,9 ± 1 y 8,9 ± 1,8, p = 0,002) y 24 horas después (9,6 ± 1,3 mg/dl, 9,8 ± 1,4 y 9 ± 1,8, p = 0,04) fueron menor en el grupo L40. Conclusiones: El tratamiento con LEDs a 40 µW/cm2/nm reduce en 12 horas la duración del tratamiento en comparación con LEDs o luz azul a 30 µW/cm2/nm.

Introduction: Hyperbilirubinemia (HB) is the main cause of admission to low risk neonatal units. New phototherapy devices (PT) allow the use of high dose of irradiance. Objective: To compare the efficacy of PT in terms of hours of treatment between blue light tubes and LEDs equipments with two levels of irradiance. Material and methods: Prospective controlled trial. Term or near-term infants with need of PT treatment according to AAP recommendations were randomized into three groups: blue lights PT with 30 µW/cm2/nm (BL) or LEDs PT with 30 µW/cm2/nm (L30) or 40 µW/cm2/nm (L40) at skin level. Results: 165 patients were included, 54 in the BL group, 56 in L30 and 55 in L40 group. Birth weight, gestational age, postnatal hours at randomization and total serum bilirubin (TSB) level at entry (18.9 ± 2 mg/dl in BL, 18.9 ± 2.2 in L30 and 19 ± 1.6 in L40) were similar between groups. Total time of PT were 54.4 ± 6.9 hours in BL, 53.4 ± 10.7 in L30 and 41.7 ± 6 in L40 (p <0.001). TSB levels at PT discontinuation (10.1 ± 1.7 mg/dl, 9.9 ± 1 and 8.9 ± 1.8, p = 0.002) and 24 hours later (9.6 ± 1.3 mg/dl, 9.8 ± 1.4 and 9 ± 1.8, p = 0.04) were lower in L40 group.Conclusions: PT treatment with LEDs at µW/cm2/nm reduced the duration of treatment in 12 hours compared with BL or LEDs at 30 µW/cm2/nm.

Oxygen therapy-use and abuse in acute myocardial infarction patients.

In August 2008, an article was published in Heart entitled, "The Routine Use of Oxygen in the Treatment of Myocardial Infarction." This article stimulated me to opine on this topic, which has been an interest of mine for many years.

Radium and uranium levels in vegetables grown using different farming management systems.

Vegetables grown with phosphate fertilizer (conventional management), with bovine manure fertilization (organic management) and in a mineral nutrient solution (hydroponic) were analyzed and the concentrations of (238)U, (226)Ra and (228)Ra in lettuce, carrots, and beans were compared. Lettuce from hydroponic farming system showed the lowest concentration of radionuclides 0.51 for (226)Ra, 0.55 for (228)Ra and 0.24 for (238)U (Bq kg(-1) dry). Vegetables from organically and conventionally grown farming systems showed no differences in the concentration of radium and uranium. Relationships between uranium content in plants and exchangeable Ca and Mg in soil were found, whereas Ra in vegetables was inversely correlated to the cation exchange capacity of soil, leading to the assumption that by supplying carbonate and cations to soil, liming may cause an increase of U and a decrease of radium uptake by plants. The soil to plant transfer varied from 10(-4) to 10(-2) for (238)U and from 10(-2) to 10(-1) for (228)Ra.

Influence of He-Ne laser therapy on the dynamics of wound healing in mice treated with anti-inflammatory drugs.

We determined the effects of helium-neon (He-Ne) laser irradiation on wound healing dynamics in mice treated with steroidal and non-steroidal anti-inflammatory agents. Male albino mice, 28-32 g, were randomized into 6 groups of 6 animals each: control (C), He-Ne laser (L), dexamethasone (D), D + L, celecoxib (X), and X + L. D and X were injected im at doses of 5 and 22 mg/kg, respectively, 24 h before the experiment. A 1-cm long surgical wound was made with a scalpel on the abdomens of the mice. Animals from groups L, D + L and X + L were exposed to 4 J (cm(2))-1 day-1 of He-Ne laser for 12 s and were sacrificed on days 1, 2, or 3 after the procedure, when skin samples were taken for histological examination. A significant increase of collagen synthesis was observed in group L compared with C (168 +/- 20 vs 63 +/- 8 mm(2)). The basal cellularity values on day 1 were: C = 763 +/- 47, L = 1116 +/- 85, D = 376 +/- 24, D + L = 698 +/- 31, X = 453 +/- 29, X + L = 639 +/- 32 U/mm(2). These data show that application of L increases while D and X decrease the inflammatory cellularity compared with C. They also show that L restores the diminished cellularity induced by the anti-inflammatory drugs. We suggest that He-Ne laser promotes collagen formation and restores the baseline cellularity after pharmacological inhibition, indicating new perspectives for laser therapy aiming to increase the healing process when anti-inflammatory drugs are used.

Influence of He-Ne laser therapy on the dynamics of wound healing in mice treated with anti-inflammatory drugs

We determined the effects of helium-neon (He-Ne) laser irradiation on wound healing dynamics in mice treated with steroidal and non-steroidal anti-inflammatory agents. Male albino mice, 28-32 g, were randomized into 6 groups of 6 animals each: control (C), He-Ne laser (L), dexamethasone (D), D + L, celecoxib (X), and X + L. D and X were injected im at doses of 5 and 22 mg/kg, respectively, 24 h before the experiment. A 1-cm long surgical wound was made with a scalpel on the abdomens of the mice. Animals from groups L, D + L and X + L were exposed to 4 J (cm²)-1 day-1 of He-Ne laser for 12 s and were sacrificed on days 1, 2, or 3 after the procedure, when skin samples were taken for histological examination. A significant increase of collagen synthesis was observed in group L compared with C (168 ± 20 vs 63 ± 8 mm²). The basal cellularity values on day 1 were: C = 763 ± 47, L = 1116 ± 85, D = 376 ± 24, D + L = 698 ± 31, X = 453 ± 29, X + L = 639 ± 32 U/mm². These data show that application of L increases while D and X decrease the inflammatory cellularity compared with C. They also show that L restores the diminished cellularity induced by the anti-inflammatory drugs. We suggest that He-Ne laser promotes collagen formation and restores the baseline cellularity after pharmacological inhibition, indicating new perspectives for laser therapy aiming to increase the healing process when anti-inflammatory drugs are used.

Re-thinking angina.

William Heberden in 1772 published "some account of the disorder of the breast" which contains the essential elements of angina pectoris as we understand it today. The number of existing cases in the U.S. population today is 6.4 million. Myocardial ischemia manifested by angina pectoris can be either acute or chronic. Patients with chronic stable angina will be the focus of this supplement. The majority of patients are symptomatic but approximately 25% can be asymptomatic. The clinical manifestations of myocardial ischemia generally are chest discomfort, arrhythmias, and LV dysfunction. Myocardial ischemia is a result of imbalance between myocardial oxygen supply and myocardial oxygen demand. High grade coronary stenosis are the usual cause of decreased oxygen supply. The classic hemodynamic factors increasing myocardial oxygen demand include hypertension and increased heart rate due to tachyarrhythmias of any etiology. Exertion is the usual precipitating cause of chronic myocardial ischemia. New information has come forward indicating that myocardial ischemia is associated with disruption of cellular sodium and calcium homeostasis. Ischemia results in a rise of intracellular sodium concentration and thus sodium overload which then activates the sodium calcium exchanger and leads to increased intracellular calcium. When this occurs there is electrical instability and mechanical dysfunction which increases oxygen demand and decreases oxygen supply. The compound Ranolazine is thought to selectively inhibit the late sodium current and attenuates the abnormalities of ventricular repolarization and contractility associated with myocardial ischemia. This compound is the first new class of anti-anginal medication approved in 25 years which may provide physicians with additional therapy for chronic stable angina along with the other anti-angina agents, beta blockers, calcium antagonists and nitrates.

Treatment options for refractory angina in patients who are not candidates for revascularization.

Patients with refractory angina are those for whom medical therapy has failed to eradicate the angina completely and who have persistent symptoms that are stable but limit their activities of daily living. Approach to management must include the elimination of the secondary causes of this condition and maximum medical therapy, and if angina persists, the consideration of other strategies. Controversy exists regarding the value of transmural myocardial laser revascularization. Enhanced external counterpulsation is clinically effective in approximately 70% of patients. Spinal cord stimulation is not being used clinically in the United States. In the United States, it is still an investigational procedure that is currently being evaluated prospectively in a randomized trial. Ranolazine, an inhibitor of sodium-dependent calcium overload, may prove to be useful in patients with refractory angina.

An academic-community cardiovascular service line affiliation: design, implementation, and performance.

Both affiliation with an academic medical center and implementation of service line management may be effective management strategies for community health care organizations. The authors describe the design, implementation, and performance of a unique combination of these two distinct strategies for cardiovascular program development in the affiliation of the University of Florida Health Science Center with Health First, a regional community-based integrated delivery system.

[Tension-free hernioplasty in the aged. A report of 94 cases]. / Ernioplastica secondo Lichtenstein nell'anziano. Contributo clinico.

BACKGROUND: Tension free inguinal hernioplasty has become the procedure of choice in the elderly. The operation of originally popularized by Lichtenstein and Shulman gives the best early result with low complication rates. METHODS: Between January 1991 and December 1996, 94 subjects over 70 with inguinal hernia were submitted to hernioplasty. The tension-free technique was adopted utilizing a polypropylene mesh. Peridural anesthesia was the method used in 67 procedures, local anesthesia in 27 procedures. RESULTS: The mean hospital stay was 48 hours (short stay surgery). Noteworthy general complications were not observed. Superficial wound infection occurred in 2 patients; superficial skin hematoma in 4 patients. No recurrences were observed (mean follow-up 60 months). The primary inguinal hernias in the aged is due to a progressive deterioration of the inguinal floor (collagenolylis, overpowers net collagen synthesis and deposition in the floor of the inguinal canal). CONCLUSIONS: Tension-free inguinal hernioplasty, originally popularized by Lichtenstein and Shulman, is simple to perform and gives excellent results with low complication rates. Current evidence suggests it as operation of choice in the elderly.

Life-threatening dystonia-dyskinesias in a child: successful treatment with bilateral pallidal stimulation.

We report a 13-year-old boy who developed severe, refractory dystonia-dyskinesias as an abrupt worsening of a previously nonprogressive movement disorder. The movements became continuous, requiring artificial respiration and continuous sedation in the intensive-care unit. Various drugs and drug combinations failed to achieve control. The child was then treated successfully with bilateral pallidal (GPi) stimulation as shown in the videotape. Four months later and without medication, the boy regained autonomous gait and audible speech; his neurologic condition continues to improve.

Antiviral effect of hyperthermic treatment in rhinovirus infection.

Human rhinoviruses (HRV) are recognized as the major etiologic agents for the common cold. Starting from the observation that local hyperthermic treatment is beneficial in patients with natural and experimental common colds, we have studied the effect of brief hyperthermic treatment (HT) on HRV replication in HeLa cells. We report that a 20-min HT at 45 degrees C is effective in suppressing HRV multiplication by more than 90% when applied at specific stages of the virus replication cycle. Synthesis of virus proteins is not affected by HT, indicating that the target for treatment is a posttranslational event. The antiviral effect is a transient cell-mediated event and is associated with the synthesis of the 70-kDa heat shock protein hsp70. Unlike poliovirus, rhinovirus infection does not inhibit the expression of hsp70 induced by heat. The possibility that hsp70 could play a role in the control of rhinovirus replication is suggested by the fact that a different class of HSP inducers, the cyclopentenone prostaglandins PGA1 and delta 12-PGJ2, were also effective in inhibiting HRV replication in HeLa cells. Inhibition of hsp70 expression by actinomycin D prevented the antiviral activity of prostaglandins in HRV-infected cells. These results indicate that the beneficial effect of respiratory hyperthermia may be mediated by the induction of a cytoprotective heat shock response in rhinovirus-infected cells.

Short-term biomarkers of tumor promotion in mouse skin treated with petroleum middle distillates.

Topical application of certain petroleum middle distillates (PMD) to mice produces skin tumors after long latency, and initiation/promotion protocols indicate that this effect is associated with their tumor promoting activity. Since induction of sustained, potentiated epidermal hyperplasia is predictive of promoting activity, five compositionally distinct PMD [hydrodesulfurized kerosene (API 81-07); hydrodesulfurized PMD (API 81-10); odorless light petroleum hydrocarbons; severely hydrotreated light vacuum distillate (LVD); and lightly refined paraffinic oil (LRPO)] were assessed for their effects on epidermal hyperplasia. PMD were administered (2 x/week for 2 weeks) to skin of CD-1 mice. Four quantitative biomarkers of epidermal hyperplasia were evaluated: epidermal thickness, number of nucleated epidermal cells per unit length of basement membrane, labeling (BrdUrd) index of epidermal cells, and induction of epidermal ornithine decarboxylase (ODC) activity. As positive controls, 12-O-tetradecanoylphorbol-13-acetate (TPA) and n-dodecane were utilized. PMD-induced skin irritation was evaluated visually and/or histopathologically. All five PMD produced dose-dependent, skin irritation and epidermal hyperplasia. On a weight basis the magnitude of the maximal PMD-induced effects was similar to that produced by n-dodecane, but > 1000-fold less than that produced by TPA. Epidermal hyperplasia and subacute skin irritancy produced by the five PMD were similar. Of the four short-term markers of tumor promotion assessed, labeling index and epidermal ODC activity were predictive of the relative promoting activities of those PMD for which tumorigenicity bioassay data are available, i.e., API 81-07 > API 81-10 > LRPO. An apparent discrepancy to the predictability of epidermal ODC activity occurred with LRPO:toluene [1:1 (v/v)]. This mixture is nontumorigenic, yet significantly induced epidermal ODC activity. This mixture, however, produced severe epidermal toxicity that precluded any meaningful analysis of short-term biomarkers in relationship to biological activity.

Asymptomatic Cardiac Ischemia Pilot (ACIP) study two-year follow-up: outcomes of patients randomized to initial strategies of medical therapy versus revascularization.

BACKGROUND: Patients with ischemia during stress testing and ambulatory ECG monitoring have an increased risk of cardiac events, but it is not known whether their prognosis is improved by more aggressive treatment with anti-ischemic drugs or revascularization. METHODS AND RESULTS: The Asymptomatic Cardiac Ischemia Pilot study randomized 558 such patients who had coronary anatomy suitable for revascularization to three treatment strategies: angina-guided drug therapy (n=183), angina plus ischemia-guided drug therapy (n=183), or revascularization by angioplasty or bypass surgery (n=192). Two years after randomization, the total mortality was 6.6% in the angina-guided strategy, 4.4% in the ischemia-guided strategy, and 1.1% in the revascularization strategy (P<.02). The rate of death or myocardial infarction was 12.1% in the angina-guided strategy, 8.8% in the ischemia-guided strategy, and 4.7% in the revascularization strategy (P<.04). The rate of death, myocardial infarction, or recurrent cardiac hospitalization was 41.8% in the angina-guided strategy, 38.5% in the ischemia-guided strategy, and 23.1% in the revascularization strategy (P<.001). Pairwise testing revealed significant differences between the revascularization and angina-guided strategies for each comparison. CONCLUSIONS: A strategy of initial revascularization appears to improve the prognosis of this population compared with angina-guided medical therapy. A larger long-term study is needed to confirm this benefit and to adequately test the potential of more aggressive drug therapy.

Effect of spray-dried yogurt and lactic acid bacteria on the initiation and promotion stages of chemically induced skin carcinogenesis in mice.

The effects of dietary spray-dried yogurt powder product (YPP) and two strains of lactic acid bacteria on the initiation and promotion stages of carcinogenesis were investigated using the 7,12-dimethylbenz[a]anthracene (DMBA)-12-O-tetradecanoylphorbol-13-acetate (TPA) mouse skin carcinogenesis model. In two independent studies, Sencar mice were fed a diet containing 86%, 43%, or 0% YPP or the 0% YPP diet supplemented with viable cultures of Lactobacillus acidophilus or bifidobacteria. Animals were initiated with a single topical application of DMBA (10 nmol). Promotion began three weeks later with twice weekly treatment of TPA (1 microgram/200 microliters acetone). During the initiation study (Study 1) the experimental diets were fed for four weeks before and one week after DMBA treatment. All mice were then switched to the AIN-76 diet. For the promotion study (Study 2) the experimental diets were begun one week after initiation and fed during the remainder of the study. Gross appearance of tumors was assessed weekly. No statistically significant differences in body weight or food disappearance were observed among the diet groups during the studies. For Studies 1 and 2, final histologically verified papilloma incidence and multiplicity and carcinoma incidence were not statistically different. These data suggest that different levels of YPP or lactic acid bacteria fed during the initiation or promotion stage of carcinogenesis do not significantly affect chemically induced skin tumor development.

Comparison of subgroups assigned to medical regimens used to suppress cardiac ischemia (the Asymptomatic Cardiac Ischemia Pilot [ACIP] Study).

This report focuses on the subset of 235 patients from the Asymptomatic Cardiac Ischemia Pilot (ACIP) study receiving randomly assigned medical therapy to treat angina and suppress ischemia detected on ambulatory electrocardiography: 121 patients received the sequence of atenolol and nifedipine, and 114 diltiazem and isosorbide dinitrate. After 12 weeks of therapy, the primary end point (absence of ambulatory electrocardiographic (ECG) ischemia and no clinical events) was reached in 47% of atenolol/nifedipine- versus 31% of diltiazem/isosorbide dinitrate-treated patients (adjusted p = 0.03). A trend to increased exercise time to ST depression was seen in the atenolol and nifedipine versus diltiazem and isosorbide dinitrate regimens (median treadmill duration 5.8 vs 4.8 minutes; p = 0.04). However, when adjusted for baseline imbalances in ambulatory ECG ischemia, the 2 medical combinations were similar in suppression of ambulatory ECG ischemia. In both medication regimens, an association between mean heart rate and ischemia on ambulatory electrocardiography after 12 weeks of treatment was observed so that patients on either regimen with a mean heart rate > 80 beats/min had ischemia detectable almost twice as often as those with a mean heart rate < 70 beats/min (p < 0.001).