The effectiveness of biofeedback-assisted relaxation in modifying sickle cell crises

Eight outpatients with sickle cell disease received six EMG and six thermal half-hour biofeedback training sessions. Statistically significant changes in the desired directions were obtained for the following variables: (a) frontalis muscle tension, (b) digital temperature, (c) frequency of headache as a crisis symptom, (d) frequency of analgesic use, (e) perceived pain intensity, (f) frequency of self-treated crises, and (g) state anxiety. Nonsignificant changes in hospital chart data were found. A 6-month posttreatment follow-up questionnaire revealed the continued effectiveness of the training received regarding headaches and mild pains.Portions of this paper were presented at the meeting of the Eastern Psychological Association, April 1984 and March 1985. The authors wish to publically thank the Ladies Auxiliary of St. Luke's-Roosevelt Hospital Center for donating tape recorders, home training relaxation tapes, and velcro thermistors to all participants. The authors are deeply grateful to Doris L. Wethers, M. D., director of the Sickle Cell Clinic at St. Luke's-Roosevelt Hospital Center for her cooperation with this study. She was especially helpful in clarifying the clinical manifestations of sickle cell disease. She was also helpful in enrolling patients and in obtaining the above-mentioned funding.     

Painful crises in sickle cell disease--patients' perspectives.

One hundred and two patients returned structured questionnaires sent to clinics for sickle cell disease in the United Kingdom in order to gain greater insight into the patients'' perception of painful crises. Most patients who suffer pain crises experience a prodromal stage that should be investigated further to find out if prophylaxis is possible. Cold, exertion, and tiredness were the most important precipitating factors. Despite the increase in the amount of knowledge about sickle cell disease in recent years, and though 29 out of 88 patients (30-40%) believed that medical services were improving, 33 out of 88 (30-40%) were still experiencing long delays in being treated in hospital. A third of patients do not seem to receive adequate pain relief.     

Predictors of success in hypertensives treated with biofeedback-assisted relaxation

This paper describes differences in response in seventeen patients with essential hypertension who participated in a treatment program consisting of electromyograph biofeedback assisted relaxation training. Responders were found to have higher treatment values of urinary and plasma cortisol, Trait Anxiety and forehead muscle tension compared to treatment failures. Responders also sustained greater decreases in plasma, and urinary cortisol after treatment. These data are discussed in light of the ability to predict which hypertensive patients may be most benefitted by a relaxation based treatment.     

Sustained effects of biofeedback-assisted relaxation therapy in essential hypertension.

The usefulness of biofeedback-assisted relaxation as an adjunct or substitute for pharmacotherapy in essential hypertension can be enhanced if the effects are shown to persist after formal treatment has ended. Patients with essential hypertension successfully treated with biofeedback-assisted relaxation were recalled for follow-up yearly after the termination of treatment. Twenty-six of 40 patients met the BP criterion for success. At one-, two-, and three-year follow-up, 31%, 38%, and 27% of the successful completers continued to meet the criterion for success. The pretreatment-posttreatment decreases in BP were accompanied by decreases in forehead muscle tension and urinary cortisol. Forehead muscle tension, urinary cortisol, and anxiety levels were significantly lower than pretreatment one year after the end of treatment. Self-report data were used to assess continued relaxation practice. No relationship was found between practice and any other dependent measure. It appears that some patients trained in biofeedback-assisted relaxation can maintain lowered blood pressure, muscle tension, anxiety, and cortisol levels over the long term; however, the role of relaxation practice in maintaining these lowered levels remains unclear.     

Sustained effects of biofeedback-assisted relaxation therapy in essential hypertension

The usefulness of biofeedback-assisted relaxation as an adjunct or substitute for pharmacotherapy in essential hypertension can be enhanced if the effects are shown to persist after formal treatment has ended. Patients with essential hypertension successfully treated with biofeedback-assisted relaxation were recalled for follow-up yearly after the termination of treatment. Twenty-six of 40 patients met the BP criterion for success. At one-, two-, and three-year follow-up, 31%, 38%, and 27% of the successful completers continued to meet the criterion for success. The pretreatment-posttreatment decreases in BP were accompanied by decreases in forehead muscle tension and urinary cortisol. Forehead muscle tension, urinary cortisol, and anxiety levels were significantly lower than pretreatment one year after the end of treatment. Self-report data were used to assess continued relaxation practice. No relationship was found between practice and any other dependent measure. It appears that some patients trained in biofeedback-assisted relaxation can maintain lowered blood pressure, muscle tension, anxiety, and cortisol levels over the long term; however, the role of relaxation practice in maintaining these lowered levels remains unclear.     

Predictors of success in hypertensives treated with biofeedback-assisted relaxation

This paper describes differences in response in seventeen patients with essential hypertension who participated in a treatment program consisting of electromyograph biofeedback assisted relaxation training. Responders were found to have higher treatment values of urinary and plasma cortisol, Trait Anxiety and forehead muscle tension compared to treatment failures. Responders also sustained greater decreases in plasma, and urinary cortisol after treatment. These data are discussed in light of the ability to predict which hypertensive patients may be most benefitted by a relaxation based treatment.We would like to thank Dr. Charles Spielberger for his permission to use the State-Trait Anxiety Inventory. We thank Michael Robinson for assistance with statistical analysis.     

Interaction of biofeedback-assisted relaxation and diuretic in treatment of essential hypertension.

Thirty patients with essential hypertension participated in a study designed to compare two treatments: diuretic medication alone (n = 10) and biofeedback assisted relaxation combined with diuretic (n = 20). One of 10 patients lowered BP with diuretic alone and 11 of 20 patients lowered BP with diuretic combined with biofeedback-assisted relaxation. The addition of the behavioral intervention to the diuretic therapy produced a decrease in blood pressure beyond that associated with the diuretic alone. The decrease in BP mediated by diuretic were related to high entry levels of BP, low anxiety, forehead muscle tension, anger expression and plasma renin activity. The BP decrease mediated by combined diuretic and biofeedback-assisted relaxation was associated with high pretreatment BP, anger controlled, low finger temperature and high/normal plasma renin activity.     

Interaction of biofeedback-assisted relaxation and diuretic in treatment of essential hypertension

Thirty patients with essential hypertension participated in a study designed to compare two treatments: diuretic medication alone (n=10) and biofeedback assisted relaxation combined with diuretic (n=20). One of 10 patients lowered BP with diuretic alone and 11 of 20 patients lowered BP with diuretic combined with biofeedback-assisted relaxation. The addition of the behavioral intervention to the diuretic therapy produced a decrease in blood pressure beyond that associated with the diuretic alone. The decreases in BP mediated by diuretic were related to high entry levels of BP, low anxiety, forehead muscle tension, anger expression and plasma renin activity. The BP decrease mediated by combined diuretic and biofeedback-assisted relaxation was associated with high pretreatment BP, anger controlled, low finger temperature and high/normal plasma renin activity.This work supported by the Northwestern Ohio Heart Association under grant No. 93132 to Dr. McGrady.     

A retrospective,follow-up study of biofeedback-assisted relaxation therapy in patients with posttraumatic headache

Although biofeedback in the treatment of migraine and tension-type headache has been widely researched, there is little research examining biofeedback therapy in posttraumatic headache (PTH). In this retrospective study, 40 subjects with PTH who had received biofeedback-assisted relaxation at our headache clinic were questioned at least 3 months following the completion of therapy. Subjects were queried about improvements in headache, increases in ability to relax and cope with pain, and overall benefits, lasting effectiveness, and continued use of biofeedback in daily life. Results indicate 53% reported at least moderate improvement in headaches; 80% reported at least moderate improvement in ability to relax and cope with pain; 93% found biofeedback helpful to some degree; 85% felt headache relief achieved through biofeedback had continued at least somewhat; and 95% stated they were continuing to use biofeedback skills in daily life. A correlation analysis revealed a negative relationship between response to biofeedback and increased chronicity of the disorder. In other words, the more chronic the disorder, the poorer the response to treatment. A stepwise regression analysis found that chronicity of the disorder and number of treatment sessions significantly affected response to treatment. Data suggest that biofeedback-assisted relaxation should at least be considered when planning treatment strategies for posttraumatic headache.We wish to express our appreciation to Sandra Tomlinson Becky Kinloch, and C. M. Bundrick for their assistance in this project.     

The effect of biofeedback-assisted relaxation training on blood pressure and selected biochemical parameters in patients with essential hypertension

The effect of EMG biofeedback-assisted relaxation on blood pressure and selected biochemical parameters was evaluated in 38 patients with essential hypertension. Training consisted of 8 weeks of biofeedback and home practice of relaxation exercises. Mean blood pressure decreased in the experimental group from 144/90 to 133/84 mm Hg while the control group remained unchanged. Statistically significant decreases in the experimental group also occurred in muscle tension levels, in plasma aldosterone, and in urinary cortisol. Both aldosterone and cortisol are secreted by the adrenal cortex. It was concluded that the technique taught to the experimental group produced a reduction in skeletal muscle tension and a decrease in stress responding mediated by the adrenal cortex.     

The effect of biofeedback-assisted relaxation training on blood pressure and selected biochemical parameters in patients with essential hypertension

The effect of EMG biofeedback-assisted relaxation on blood pressure and selected biochemical parameters was evaluated in 38 patients with essential hypertension. Training consisted of 8 weeks of biofeedback and home practice of relaxation exercises. Mean blood pressure decreased in the experimental group from 144/90 to 133/84 mm Hg while the control group remained unchanged. Statistically significant decreases in the experimental group also occurred in muscle tension levels, in plasma aldosterone, and in urinary cortisol. Both aldosterone and cortisol are secreted by the adrenal cortex. It was concluded that the technique taught to the experimental group produced a reduction in skeletal muscle tension and a decrease in stress responding mediated by the adrenal cortex.This work was supported by the Northwestern Ohio Heart Association Grant No. 93298. It was presented as a citation paper at the meetings of the Biofeedback Society in 1979 and 1980.     

The origin of sickle cell alleles in Israel

Summary Molecular genetic studies were undertaken to determine the source of chromosomes carrying the sickle cell allele in Israeli patients. Analysis of restriction fragment length polymorphism (RFLP) patterns (haplotypes) along the -globin gene cluster was performed on 31 sickle chromosomes obtained from 10 unrelated families living in Israel. One is a Caucasian Jewish family, recently found to be carrying the sickle allele, and the other 9 are Arab families of various communities. The Jewish family, previously noted not to carry African red blood cell markers, was discovered to have the most common African haplotype of the -globin gene cluster, Benin. Similarly, 8 of the Arab families were also found to carry the Benin haplotype, whereas the ninth has the CAR (Central African Republic or Bantu) haplotype. The results suggest that sickle alleles in Israel originated in Africa, probably in two different regions, and migrated north into Arab and Jewish populations.     

The neurotoxic effect of sickle cell hemoglobin

A growing body of experimental evidence suggests that the oxidative neurotoxicity of hemoglobin A may contribute to neuronal loss after CNS hemorrhage. Several hemoglobin variants, including hemoglobin S, are more potent oxidants in cell-free systems. However, despite the increased incidence of hemorrhagic stroke associated with sickle cell disease, little is known of the effect of hemoglobin S on cells of neural origin. In the present study, its toxicity was quantified and directly compared with that of hemoglobin A in murine cortical cell cultures. Reactive oxygen species production, as assessed by cellular fluorescence after treatment with dihydrorhodamine 123, was significantly increased by exposure to 10 μM hemoglobin S for 2-4 h. Neuronal death, as measured by propidium iodide staining and lactate dehydrogenase release, commenced at 4 h; for a 20-h exposure, the EC₅₀ was approximately 0.71 μm. Glial cells were not injured. Cell death was completely blocked by iron chelation with deferoxamine or phenanthroline. Direct comparison of sister cultures exposed to either hemoglobin A or hemoglobin S revealed a similar amount of cell injury in both groups. A significant difference was consistently observed only after treatment with 1 μM hemoglobin for 20 h, which resulted in death of approximately one third more neurons with hemoglobin S than with hemoglobin A. The results of this study suggest that sickle cell hemoglobin is neurotoxic at physiologically relevant concentrations. This toxicity is iron-dependent, oxidative, and quantitatively similar to that produced by hemoglobin A.     

The role of fibrocytes in sickle cell lung disease

Background

Interstitial lung disease is a frequent complication in sickle cell disease and is characterized by vascular remodeling and interstitial fibrosis. Bone marrow-derived fibrocytes have been shown to contribute to the pathogenesis of other interstitial lung diseases. The goal of this study was to define the contribution of fibrocytes to the pathogenesis of sickle cell lung disease.

Methodology/Principal Findings

Fibrocytes were quantified and characterized in subjects with sickle cell disease or healthy controls, and in a model of sickle cell disease, the NY1DD mouse. The role of the chemokine ligand CXCL12 in trafficking of fibrocytes and phenotype of lung disease was examined in the animal model. We found elevated concentration of activated fibrocytes in the peripheral blood of subjects with sickle cell disease, which increased further during vaso-occlusive crises. There was a similar elevations in the numbers and activation phenotype of fibrocytes in the bone marrow, blood, and lungs of the NY1DD mouse, both at baseline and under conditions of hypoxia/re-oxygenation. In both subjects with sickle cell disease and the mouse model, fibrocytes expressed a hierarchy of chemokine receptors, with CXCR4 expressed on most fibrocytes, and CCR2 and CCR7 expressed on a smaller subset of cells. Depletion of the CXCR4 ligand, CXCL12, in the mouse model resulted in a marked reduction of fibrocyte trafficking into the lungs, reduced lung collagen content and improved lung compliance and histology.

Conclusions

These data support the notion that activated fibrocytes play a significant role in the pathogenesis of sickle cell lung disease.     

Red blood cell lactate transport in sickle disease and sickle cell trait.

This study determined and compared rates and mechanisms of lactate transport in red blood cells (RBCs) of persons with 1) sickle cell disease (HbSS), 2) sickle cell trait (HbAS), and 3) a control group (HbAA). Blood samples were drawn from 30 African-American volunteers (10 HbSS, 10 HbAS, 10 HbAA). Lactate influx into RBCs was measured by using [14C]lactate at six (2, 5, 10, 15, 25, and 40 mM) unlabeled lactate concentrations. The monocarboxylate transporter pathway was blocked by p-chloromercuriphenylsulfonic acid to determine its percent contribution to total lactate influx. Generally, total lactate influx into RBCs from the HbSS group was significantly greater than influx into RBCs from HbAS or HbAA, with no difference between HbAS and HbAA. Faster influx into HbSS RBCs was attributed to increased monocarboxylate transporter activity [increased apparent Vmax (V'max)]. V'max (4.7 +/- 0.6 micromol x ml(-1) x min(-1)) for HbSS RBCs was significantly greater than V'max of HbAS RBCs (2.9 +/- 1.5 micromol x ml(-1) x min(-1)) and HbAA RBCs (2.0 +/- 0.5 micromol x ml(-1) x min(-1)). Km (42.8 +/- 8 mM) for HbSS RBCs was significantly greater than Km (27 +/- 12 mM) for HbAA RBCs. We suspect that elevated erythropoietin levels in response to chronic anemia and/or pharmacological treatment (erythropoietin injections, hydroxyurea ingestion) is the underlying mechanism for increased lactate transport capacity in HbSS RBCs.