Impact of autonomic and self-regulation on cancer-related fatigue and distress in breast cancer patients--a prospective observational study.

PURPOSE: Cancer-related fatigue (CRF) has a major impact on the quality of life in breast cancer patients (BC). So far, only a few prospective studies have investigated the effect of adaptive salutogenic mechanisms on CRF. The aim of our study was to evaluate the possible prospective influence of autonomic Regulation (aR) and self-regulation (SR) on CRF and distress in long-term survivors. METHODS: 95 BC and 80 healthy female controls (C) had been included in the observational study between 2000 and 2001 and completed the questionnaires on aR, SR and Hospital Anxiety and Depression Scale (HADS). Of these, 62 BC, and 58 C participated in the re-evaluation 6.6 years later: 16 participants were deceased (14 BC and 2 C). During follow-up, participants were requested to answer questions involving (Cancer Fatigue Scales) CFS-D, aR, SR and HADS. Multiple regression analysis was used to evaluate the influence of aR, SR, age, Charlson co-morbidity-index and diagnosis on CFS-D and HADS, and to select further potentially relevant factors. RESULTS: High aR values showed significant effects, namely inverse relationships with CFS-D, cognitive fatigue, anxiety and depression. SR showed a reduced influence on anxiety and depression (all p < 0.05). CONCLUSIONS: Autonomic regulation might have an independent, reductive influence on global fatigue, cognitive fatigue and--together with self-regulation--it seems to have a protective influence on anxiety and depression. The connection between these parameters is still unclear and awaits further evaluation. IMPLICATION FOR CANCER SURVIVORS: AR seems to be a prognostic factor in breast cancer survivors, capable of reducing cancer-related fatigue and self-regulation distress as well. Further research is necessary in order to show how aR can be improved by therapeutic interventions.

Metacarpal thickness, width, length and medullary diameter in children--reference curves from the First Zürich Longitudinal Study.

SUMMARY: Metacarpal thickness (T), width (W), length (L) and medullary diameter (M) were measured in 3,121 X-rays from 231 healthy Caucasian children aged 3 to 19 years and analysed for bone age, age, height, weight and gender-related characteristics, showing highly differentiated growth patterns with prepubertal dips. Reference data for the four metacarpal measures are presented. INTRODUCTION: The aim of the study was to create and explore a reference database for metacarpal T, W, L and M in children. METHODS: Three thousand one hundred twenty-one left-hand X-rays (1,661 from boys) from 231 healthy Caucasian subjects (119 boys) aged 3 to 19 years were analysed by BoneXpert, a programme for automatic analysis of hand X-rays and bone age (BA; in years). RESULTS: In boys, growth of T, W and L shows a prepubertal decrease from BA 7 to 13 and then accelerates again. In girls, the same is seen only for T starting from BA 8 to 11, whereas W and L grow at a declining rate. M shows steady growth until BA 10.5 in girls and BA 13.5 in boys and then grows smaller in both. W is greater in boys from BA 6 onwards, while L is greater in girls from BA 9 to 13 and T from BA 11 to 14. BA is reflected best by L until start of puberty and by T and L thereafter. CONCLUSION: T, W, L and M show highly differentiated growth patterns. These reference data provide a basis for further research into skeletal development and the management of hormone therapies in children.

Validation of the self regulation questionnaire as a measure of health in quality of life research.

OBJECTIVES: Several epidemiological studies address psychosomatic self regulation as a measure of quality of life aspects. However, although widely used in studies with a focus on complementary cancer treatment, and recognized to be associated with better survival of cancer patients, it is unclear what the self regulation questionnaire exactly measures. DESIGN AND SETTING: In a sample of 444 individuals (27% healthy, 33% cancer, 40% other internal diseases), we performed reliability and exploratory factor analyses, and correlated the 16-item instrument with external measures such as the Hospital Anxiety and Depression Scale, the Herdecke Quality of Life questionnaire, and autonomic regulation questionnaire. RESULTS: The 16-item pool had a very good internal consistency (Cronbach's alpha = 0.948) and satisfying/good (r subsetrt = 0.796) test-retest reliability after 3 months. Exploratory factor analysis indicated 2 sub-constructs: (1) Ability to change behaviour in order to reach goals, and (2) Achieve satisfaction and well-being. Both sub-scales correlated well with quality of life aspects, particularly with Initiative Power/Interest, Social Interactions, Mental Balance, and negatively with anxiety and depression. CONCLUSIONS: The Self Regulation Questionnaire (SRQ) was found to be a valid and reliable tool which measures unique psychosomatic abilities. Self regulation deals with competence and autonomy and can be regarded as a problem solving capacity in terms of an active adaptation to stressful situations to restore well-being. The tool is an interesting option to be used particularly in complementary medicine research with a focus on behavioural modification.

Adaptation of the Herdecke Quality of Life questionnaire towards quality of life of cancer patients.

Although instruments for the measurement of quality of life (QoL) do exist for cancer patients, factors like sleepiness or digestion are only marginally addressed. We intended to adapt the Herdecke Quality of Life (HLQ) towards these aspects in a multi-centre cross-sectional validation study. A group of 293 subjects [79% female, age: 55.9 +/- 13.4 years; 146 cancer patients, 28 patients with rheumatic diseases and a healthy control group (n = 119)]. Structural relations between the items were detected by factor and reliability analyses. For external validation, correlations with the hospital anxiety and depression scale (HADS), self-regulation score (SRS) and the Marburger short questionnaire on chronotypology (MQC) were performed, and test-retest reliability was calculated. Factor analysis found three sub-scales: physical abilities (PA) (Cronbach's alpha = 0.90), sleep quality (SQ) (Cronbach's alpha = 0.89) and digestive well-being (DWB) (Cronbach's alpha = 0.80). Sleep quality correlated well with HADS-anxiety (r =-0.52), PA with HADS-depression (r =-0.49). We found moderate correlations of PA and SQ with SRS, while the HLQ scales did not correlate with the MQC. Analysis of test-retest reliability resulted in values of r = 0.757 for PA, r = 0.715 for SQ and r = 0.603 for DWB. The HLQ-cancer suits to measure unique features of cancer-related QoL aspects. In future studies it has to be tested in larger samples of cancer patients.

Validation of a questionnaire measuring the regulation of autonomic function.

BACKGROUND: To broaden the range of outcomes that we can measure for patients undergoing treatment for oncological and other chronic conditions, we aimed to validate a questionnaire measuring self-reported autonomic regulation (aR), i.e. to characterise a subject's autonomic functioning by questions on sleeping and waking, vertigo, morningness-eveningness, thermoregulation, perspiration, bowel movements and digestion. METHODS: We administered the questionnaire to 440 participants (female symbol: N = 316, male symbol: N = 124): 95 patients with breast cancer, 49 with colorectal cancer, 60 with diabetes mellitus, 39 with coronary heart disease, 28 with rheumatological conditions, 32 with Hashimoto's disease, 22 with multiple morbidities and 115 healthy people. We administered the questionnaire a second time to 50.2% of the participants. External convergence criteria included the German version of the Hospital Anxiety and Depression Scale (HADS-D), a short questionnaire on morningness-eveningness, the Herdecke Quality of Life Questionnaire (HLQ) and a short version questionnaire on self-regulation. RESULTS: A principal component analysis yielded a three dimensional 18-item inventory of aR. The subscales orthostatic-circulatory, rest/activity and digestive regulation had internal consistency (Cronbach-alpha: ralpha = 0.65 - 0.75) and test-retest reliability (rrt = 0.70 - 85). AR was negatively associated with anxiety, depression, and dysmenorrhoea but positively correlated to HLQ, self-regulation and in part to morningness (except digestive aR) (0.49 - 0.13, all p < 0.05). CONCLUSION: An internal validation of the long-version scale of aR yielded consistent relationships with health versus illness, quality of life and personality. Further studies are required to clarify the issues of external validity, clinical and physiological relevance.

Persistent inward currents in motoneuron dendrites: implications for motor output.

The dendrites of motoneurons are not, as once thought, passive conduits for synaptic inputs. Instead they have voltage-dependent channels that provide the capacity to generate a very strong persistent inward current (PIC). The amplitude of the PIC is proportional to the level of neuromodulatory input from the brainstem, which is mediated primarily by the monoamines serotonin and norepinephrine. During normal motor behavior, monoaminergic drive is likely to be moderately strong and the dendritic PIC generates many of the characteristic features of motor unit firing patterns. Most of the PIC activates at or below recruitment threshold and thus motor unit firing patterns exhibit a linear increase just above recruitment. The dendritic PIC allows motor unit derecruitment to occur at a lower input level than recruitment, thus providing sustained tonic firing with little or no synaptic input, especially in low-threshold units. However the dendritic PIC can be readily deactivated by synaptic inhibition. The overall amplification due to the dendritic PIC and other effects of monoamines on motoneurons greatly increases the input-output gain of the motor pool. Thus the brainstem neuromodulatory input provides a mechanism by which the excitability of motoneurons can be varied for different motor behaviors. This control system is lost in spinal cord injury but PICs nonetheless recover near-normal amplitudes in the months following the initial injury. The relationship of these findings to the cause of the spasticity syndrome developing after spinal cord injury is discussed.

Pretreatment with thyroxine (10-(8) parts by weight) enhances a 'curative' effect of homeopathically prepared thyroxine (10-(13)) on lowland frogs.

We studied the influence of a moderate homeopathically prepared thyroxine dilution (final concentration in the basin water 10-(13) parts by weight) on the metamorphosis of lowland Rana temporaria which had been hyperstimulated with thyroxine. Two groups of animals were pretreated by immersing them in a molecular thyroxine dilution (10-(8) parts by weight). This pretreatment speeds up development, as is well known. In accordance with the homeopathic/isopathic idea of detoxication or cure, the same hormone was then diluted and agitated in successive steps for further treatment. This homeopathically prepared dilution was administered at 24-hour intervals to one of the groups. An analogously prepared blank solution was used for the control group. Our hypothesis, which was derived from earlier studies, was that animals treated with the test solution would metamorphose more slowly than the control animals, i.e. that the homeopathically prepared thyroxine would have a 'curative' effect. In this new series of experiments this hypothesis was examined by 3 independent researchers. In the experiments carried out by 2 of the 3 researchers the number of animals that reached the four-legged stage at defined points in time was smaller in the group treated with homeopathically prepared thyroxine. In the third laboratory no difference was found between the groups. However, the overall inhibiting effect was statistically significant and more pronounced than in earlier, less promising studies and in parallel experiments in which nonprestimulated animals had been used. Other studies carried out by the 3 researchers involved animals from highland biotopes, where the natural environment probably induces a greater sensitivity towards thyroxine or higher thyroxine levels. These animals reacted to the homeopathically prepared thyroxine with a slowing down of metamorphosis, even when they had not been prestimulated with a molecular dose of the hormone. This effect was observed in all 3 laboratories and is consistent with the results of previous studies.

[The effects of Cardiodoron on cardio-respiratory coordination--a literature review]. / Wirkung von Cardiodoron(R) auf die kardiorespiratorische Koordination - ein Literaturüberblick.

BACKGROUND: In healthy subjects self-regulation of the organism establishes the order of rhythmical functions. This self-regulation is altered in patients suffering from idiopathic orthostatic syndrome resulting from disturbances of functional aspects only. Thus the cardio-respiratory coordination, which may serve as the representative of the order of rhythmical functions, is modified. OBJECTIVE: In the case of idiopathic orthostatic syndrome the anthroposophic medicine offers the medicament Cardiodoron(r). Does it stimulate self-regulation in order to normalise the cardio-respiratory coordination? MATERIAL AND METHODS: This claim is analysed by a systematic review of the literature. Only those publications were considered where the cardio-respiratory coordination was analysed in studies with patients or healthy subjects. RESULTS: The methods of the studies with patients and healthy subjects vary strongly. Nevertheless, a normalisation of the cardio-respiratory coordination could be found in studies with patients suffering from idiopathic orthostatic syndrome as well as in studies with healthy subjects. CONCLUSION: The studies show that the use of the medicament results in a normalisation of the cardiorespiratory coordination. By stimulating the self-regulation the medicament leads to an improvement of the order of rhythmical functions in the human organism.

Heart rate dynamics and cardiorespiratory coordination in diabetic and breast cancer patients.

Objective of this study was to evaluate cardiac autonomic function in female breast cancer patients on the basis of linear and non-linear heart rate variability (HRV) as well as on musical heart rate rhythmicity. The latter method has been recently developed and enables particularly the quantification of cardiorespiratory coordination solely on the basis of ECG recordings. To provide a broad basis of comparability, 37 breast cancer patients were compared with 37 age-matched healthy women and 40 age-matched female diabetic patients who serve as pathological controls. During night sleep, all parameters showed a tendency towards lower variability, complexity or rhythmicity of HRV in cancer patients. The most prominent alterations were found for the binary pattern predominance (PP) and for the ratio of heart rate and respiration. In particular, when comparing metastasized and non-metastasized cancer patients, the discriminatory power of binary heart rate rhythmicity emerges: the histograms of 1-h intervals during night sleep with a predominance of cyclically recurrent phase locking patterns unveiled a clear transition from higher to lower cardiorespiratory coordination ratios and to a loss of coordination capability in metastasized patients.

[Development of body weight, vegetative autonomous system, and breast cancer]. / Körpergewichtsenstwicklung, Vegetativum und Mammakarzinom.

In a case-control study the patterns of body mass and autonomic tone in the premorbid lifetime of breast cancer patients were analyzed retrospectively. Premenopausal breast cancer patients are remarkably thin and show patterns of an ergotropic predominance in premorbid lifetime. Their body mass index and constitution does not agree with the risk factor 'obesity' and the traditionally expected predominance of trophotropy. Furthermore, it turned out that in puberty these patients had a discontinuous change of their body weight. As reported at the time of diagnosis, in women with postmenopausal breast cancer the risk factor 'obesity' seems to be true. However, in premorbid lifespan overweight could not be detected. Therefore, the independent risk factor 'weight gain' is supposed for periclimacteric phase. These women do not show indicators of trophotropic predominance but weak signs of ergotropy and eveningness.

Effect of small doses of iodine on thyroid function in patients with Hashimoto's thyroiditis residing in an area of mild iodine deficiency.

OBJECTIVE: Several studies have suggested that iodine may influence thyroid hormone status, and perhaps antibody production, in patients with autoimmune thyroid disease. To date, studies have been carried out using large amounts of iodine. Therefore, we evaluated the effect of small doses of iodine on thyroid function and thyroid antibody levels in euthyroid patients with Hashimoto's thyroiditis who were living in an area of mild dietary iodine deficiency. METHODS: Forty patients who tested positive for anti-thyroid (TPO) antibodies or with a moderate to severe hypoechogenic pattern on ultrasound received 250 microg potassium iodide daily for 4 months (range 2-13 months). An additional 43 patients positive for TPO antibodies or with hypoechogenicity on ultrasound served as a control group. All patients were TBII negative. RESULTS: Seven patients in the iodine-treated group developed subclinical hypothyroidism and one patient became hypothyroid. Three of the seven who were subclinically hypothyroid became euthyroid again when iodine treatment was stopped. One patient developed hyperthyroidism with a concomitant increase in TBII titre to 17 U/l, but after iodine withdrawal this patient became euthyroid again. Only one patient in the control group developed subclinical hypothyroidism during the same time period. All nine patients who developed thyroid dysfunction had reduced echogenicity on ultrasound. Four of the eight patients who developed subclinical hypothyroidism had TSH concentrations greater than 3 mU/l. In 32 patients in the iodine-treated group and 42 in the control group, no significant changes in thyroid function, antibody titres or thyroid volume were observed. CONCLUSIONS: Small amounts of supplementary iodine (250 microg) cause slight but significant changes in thyroid hormone function in predisposed individuals.

[Determination of respiratory frequency from respiratory sinus arrhythmia]. / Die Bestimmung der Atemfrequenz aus der respiratorischen Sinusarrhythmie (RSA).

In the clinical setting, the observation of undisturbed spontaneous respiration and direct measurement of an "unbiased" respiratory rate is not a practical option. However, the respiratory modulation of the heart rate (respiratory sinus arrhythmia, RSA) offers a possibility of recording the respiratory rate indirectly. The present work introduces a novel procedure for extracting the respiratory rate from the ECG, and compares the results thus obtained with those of a previously applied method. The latter is based on the determination of dominant peaks in the amplitude spectrum of a five-minute RR interval time series. The new method presented here is based on the band pass filtering of a one-minute RR interval time series with subsequent analysis of the maxima, minima and zero crossings of the resulting RSA curve. The methods were compared by determining the respiratory rates of 16 healthy male subjects measured in 15 different experimental situations, including spontaneous and controlled breathing. The respiratory rate as determined by thermistor recording of nasal breath temperature was used as control. The mean deviation from directly measured respiratory rate was 2.9 min-1 for the new and 7.2 min-1 for the previous method. The new method proved superior under all conditions except controlled breathing at low frequencies. The present study thus demonstrates the high precision of respiratory rate determined indirectly by analysing the RSA curve. Since it requires no special instrumentation, this procedure is ideally suited for clinical application, and permits the continuous recording of respiratory rate over long periods of time.

Quality of life and circadian variation of heart rate and heart rate variability in short-term survivors and nonsurvivors after acute myocardial infarction.

The purpose of this study was the simultaneous examination of the quality of life and changes in heart rate (HR) variables of patients immediately following acute myocardial infarction (AMI). Quality of life, estimated on a rating scale assessing the patients' well-being, as well as the circadian rhythm of their HR and HR variability, were determined within the first 3 days and at approximately 3 weeks after admission and the results were related to survival. The quality of life within the first 3 days post AMI was low in both the surviving (n = 42) and the nonsurviving (n = 5) patients but only the scores of the survivors increased significantly over the following three weeks. The HR of the survivors, initially lower than that of the nonsurvivors, decreased significantly at 3 weeks and a normal circadian pattern had developed. The HR variability of the survivors within the first 3 days was significantly higher than that of the nonsurvivors and had developed a clear circadian pattern after 3 weeks. It is concluded that in patients with AMI such diverse clinical aspects as quality of life and circadian patterns of HR and HR variability can be assessed meaningfully immediately post AMI and may find common expression in changes in sympathovagal balance.

Thyroid sonography in autoimmune thyroiditis. A prospective study on 123 patients.

Thyroid sonography was used to assess 2322 patients attending our clinic over a 3-year period. Sonography, in combination with clinical and laboratory findings, enabled us to detect autoimmune thyroiditis in 123 patients, 67 of whom could be classified as euthyroid, 17 as latent hypothyroid, and 39 as overtly hypothyroid. Consequently without the use of sonography (or thyroid antibody measurements) it would not have been possible to make a diagnosis in over half of our patients with autoimmune thyroiditis. Sonography was also of considerable value in establishing the absence of autoimmune thyroiditis as out of the 2322 patients we examined, autoimmune thyroiditis could be excluded on the basis of sonography alone (absence of diffuse hypoechoicity) in 1962 (84%). Thyroid volume ranged from less than 5 to 112 ml with the majority of patients having a volume of 21-30 ml and the overtly hypothyroid group showing a shift to smaller volumes. The data suggested that thyroid volume changes over the range of the disease from euthyroid to overtly hypothyroid.

Ultrastructural aspects of striated muscle fibers in health and disease.

The application of electron microscopy to skeletal muscle is pertinent to 1. cytological analysis of normal muscle fibers; 2. cytopathology of muscle fibers; 3. systematic ultrastructural analysis of classic muscle diseases; 4. ultrastructure of muscle fiber inclusions; 5. neuromuscular conditions classified by electron microscopy; 6. diagnosis of individual muscle biopsies.

Congenital muscular dystrophy (CMD) - a collagen formative disease?

Muscle biopsies of 5 patients with congenital muscular dystrophy (CMD) (8 months to 3 years old) were examined by electron microscopy to determine ultrastructural abnormalities of the muscle as well as of the connective tissue cells. Two populations of muscle fibers were observed in each biopsy. Besides muscle fibers with normal or enlarged diameters there were frequently very small muscle cells indicating immaturity. The most interesting findings in each biopsy were myofibroblast-like cells exhibiting active protein synthesis. Large amounts of collagen fibrils with abnormal diameters as well as accumulation of elastic fibrils within the endomysium in CMD suggest abnormalities in collagen synthesis.