[A study of psychoneuroendocrinological effects of music therapy].

The objective evaluation of Psychoneuroendocrinological effects of music is performed in listening and performing. Subjects were classified into 3 groups; a control group and performance/listening groups voluntarily in each 10 subjects. Urine 17-KS-S (abbreviated S) and 17-OHCS (abbreviated OH) were measured before (phase I), after the experiments (phase II) and on the following morning (phase III). They enjoyed listening to their favorite music by stereo sets or performing favorite music instruments. No directions were done on the quality of music. OH showed decreasing effects in both control and performance/listening groups. S showed significant increase in listening group. From a rise of S/OH a wear and tear by stress and a skewness of balance of restoration were corrected. Music is considered that it contributed to relaxation from stress and a wear and tear by the stress and correction of balance of restoration. The fact that the efficacy persisted until the morning of the following day indicates the efficacy persists for a relatively long period of time.

A natural history of adrenocorticotropin-independent bilateral adrenal macronodular hyperplasia (AIMAH) from preclinical to clinically overt Cushing's syndrome.

A 49-year-old man was referred to our hospital for the treatment of gallstones in 1993. Bilateral adrenal nodular masses were detected incidentally by abdominal computed tomography. He had no clinical signs of Cushing's syndrome such as central obesity, striae of skin and diabetes mellitus. We performed cholecystectomy and partial adrenalectomy of right adrenal gland as a biopsy, and diagnosed him as preclinical Cushing's syndrome due to adrenocorticotropin-independent bilateral adrenal macronodular hyperplasia (AIMAH) based on endocrinological and histological examinations. We followed him up for 7 years. During the observation period, the sizes of both adrenal glands increased gradually, and finally serum cortisol level increased beyond normal range, and he showed a Cushingoid appearance such as moon face and central obesity. His skin became atrophic and very fragile, and the bone mineral density of his lumbar spine was extremely low. Serum cortisol level was elevated, and plasma ACTH level was always suppressed. Urinary excretion of 17-hydroxycorticosteroid and free cortisol were increased. Diurnal rhythm of cortisol and ACTH was completely lost and high dose (8 mg/day) dexamethasone did not suppress urinary 17-hydroxycorticosteroid excretion. He became clinically overt Cushing's syndrome. We recommended total adrenalectomy, but he refused it. It is important to know the natural history of preclinical Cushing's syndrome due to AIMAH when choosing an adequate treatment.

[17-ketosteroid sulfates and its application to kampo-medicine].

Traditional oriental medicine tells us that everything is interrelated and consists of combinations of opposing factors, "Yin-Yang". So we need to evaluate the normal state and pathologic condition from the perspective of dynamic hormone balance between cortisol and DHEA which are opposing and physiologically very important. Cortisol has a more functional side and is considered Yang, while DHEA has a more material side and is considered Yin. We tried to explain the concepts of KAMPO which include SHO (Yin-Yang. Excess-Deficiency), the 6 Stages of Disease and Deficiency of the Kidney, by measuring urinary 17-OHCS and 17-KS-S, metabolites of cortisol and DHEA. We think our effort may develop a good objective indicator of KAMPO's diagnosis and be useful for selecting of treatment.

The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). I. A Pilot study of the new vitamin C infusion treatment with a volunteer CFS patient.

A series of publications from our laboratory have indicated that the practice of megadose vitamin C drip infusion treatment enhanced the activity of endogenous glucocorticoids in such a way as to improve the clinical course of allergy and autoimmune disease-a disease entity that is known to respond to the therapeutic effect of glucocorticoids. The present paper represents an extention of our vitamin C studies, and intends to investigate the problem whether or not chronic fatigue syndrome (CFS), an acquired immunodeficiency disease, can also be counted as one of the candidate diseases for the vitamin C infusion treatment. We prepared two kinds of vitamin C infusion sets for the clinical use: the dehydroepiandrosterone-annexed vitamin C infusion set (the new set) and the annex-free vitamin C infusion set (the old set). The new set was expected to enhance the endogenous activities of both glucocorticoids and gonadal steroids. We followed the clinical course of a male CFS patient using the old and new vitamin C infusion sets, and with and without the oral intake of erythromycin and chloramphenico. Results obtained are as follows: a) the observation period of a study subject covered a period of August 1995 to May 1996. Combination of pneumonia signs and dermatomyositis signs marked the onset of his CFS. b) Old infusion treatment together with the short term antibiotics treatment was found effective for the control of pneumonia in the first stage of the disease (from August to October, 1995). c) Signs of pneumonia recurrence gradually became eminent in the second stage of disease (from November, 1995, to January, 1996) in spite of the moderate frequency of the old treatment together with stepwise prolongation of the antibiotics treatment. d) The alternate practice of the old and new infusion treatments together with the long-term antibiotics treatment, as conducted in the 3rd stage of disease (from February to May, 1996) led to substantial extinction of pneumonia signs (leucocytosis, tachycardia etc). e) The practice of the new infusion treatment markedly increased the excretion of both 17-ketosteroids and 17-hydroxycorticosteroids in the urine. Evidence was also available to indicate that the dehydroepiandrosterone annex was converted to testosterone, which in turn made a contribution to the control of CFS. f) The immunological survey of lymphocyte subsets including NK cell percent failed to find a coherent change in a study subject with CFS. In conclusion, the above results could be taken as evidence to indicate that the new vitamin C infusion treatment effectuates the clinical control of CFS by fortifying the endogenous activities of both cortisol and testosterone. The significance of parallelism between pulmonary infection and CFS, as observed in the clinical course of the test subject, was discussed in the light of the focal infection theory of nephritis.

Lysine vasopressin stimulation of cortisol secretion in patients with adrenocorticotropin-independent macronodular adrenal hyperplasia.

We present two patients with Cushing's syndrome due to ACTH-independent macronodular adrenal hyperplasia who showed marked plasma cortisol response to lysine-8-vasopressin (LVP) injection (from 930 and 731 pmol/L to 2177 and 1920 pmol/L, respectively), while plasma ACTH levels remained undetectable. The ACTH independence of cortisol secretion in the two patients was determined from the following endocrinological findings. Plasma cortisol levels were not increased by corticotropin-releasing hormone injections and were not suppressed by high dose (16 mg) dexamethasone administrations. The plasma ACTH levels, measured by two independent sensitive immunoassays, were persistently undetectable even after corticotropin-releasing hormone injection, metyrapone administration, and bilateral adrenalectomy. The particular pathological finding of the two cases, atrophic lesions in nonnodular parts of the adrenal cortexes, also indicated ACTH independence of the macronodular hyperplasia. In vitro examination revealed a direct effect of LVP on cortisol secretion from the adrenal cells of the macronodules. We also examined seven patients with Cushing's syndrome caused by adrenal adenoma and found a statistically significant plasma cortisol response to LVP injection. The direct effect of LVP was also demonstrated in cultured adenoma cells. In conclusion, we discovered a direct adrenal effect of LVP on cortisol secretion in patients with ACTH-independent macronodular hyperplasia and, to a lesser extent, in patients with cortisol-producing adrenal adenoma. The cortisol response to LVP may serve to facilitate their diagnosis and choice of therapy.

[The effect of fatty compounds with different ratios of the polyunsaturated fatty acids of the omega-3 and omega-6 families on the expression of food-related anaphylaxis, on the liver cytochrome P-450 system and on 17-hydroxycorticosteroid metabolism in guinea pigs]. / Vliianie zhirovykh kompozitsii s razlichnym sootnosheniem polinenasyshchennykh zhirnykh kislot semeistv omega-3 i omega-6 na vyrazhennost' pishchevoi anafilaksii, sistemu tsitokhroma P-450 pecheni i metabolizm 17-oksikortikosteroidov u morskikh svinok.

The effect of fat composition with a different ratio of polyunsaturated fatty acids of families omega 3 and omega 6 on expression of experimental dietary anaphylaxis, liver monooxygenase system and metabolism of 17-oxycorticosteroides (17-OCS) in guinea-pig have been investigated. Fat components in experimental diets were presented by sunflower, ichthyene oils and mix of these oils in the ratio 1:1. A ratio of PUFA of a family omega 6 to omega 3 in diets were 64,0; 0,13 and 2,64. It was shown that a burden of dietary anaphylaxis were reduced significantly at the introduction in diets of sunflower oil.ulakcuu is authentically reduced. Simultaneously a marked increase of a ratios P-450B to P-450L and b5 to P-450 and reduction of a hexenal sleep duration were determined. The amount of excreted polar 17-OCS was also decreased in animals fed sunflower oil. Probable mechanisms of hypoallergenic action of dietary sunflower oil were conditioned by reorganization of liver cytochrome P-450 system and respective alterations of 17-OCS metabolism are discussed.

Formestane: an effective first-line endocrine treatment for advanced breast cancer.

Formestane, a new selective aromatase inhibitor devoid of severe side-effects, has been shown to be active in patients with advanced breast cancer. To investigate the clinical activity and endocrinological effects of formestane as a first-line treatment, 52 patients were administered two different doses: 24 received 250 mg formestane and 28 received 500 mg formestane i.m. fortnightly. All of the patients had a performance status of 2 or less (ECOG scale), 34 (65%) had a disease-free interval of at least 2 years and 21 (40%) were both oestrogen-receptor- and progesterone-receptor-positive; 20 patients received hormone and 13, received chemotherapeutical adjuvant treatment. Objective responses were obtained in 8 patients in the 250-mg group (33%; 95% CI: 14%-52%) and in 13 patients in the 500-mg group (46%; 95% CI: 28%-64%). The median response duration in the two groups was respectively 11 and 12 months. E2 serum levels of oestradiol had significantly (P < 0.001) decreased to more than 40% below the baseline value in both groups after 15 days of treatment, and remained unchanged thereafter. Local and systemic tolerability was satisfactory. We conclude that formestane is an effective and well-tolerated agent in previously untreated patients, and that these results should be confirmed by further studies.

The relationship of urinary and plasma androgens to steroid receptors and menopausal status in breast cancer patients and their influence on survival.

The relationships between urinary 11-desoxy-17-oxo steroids (11-DOS), the ratio of 11-DOS to urinary 17-hydroxycorticosteroids (urinary discriminant ratio), plasma levels of the adrenal androgens dehydroepiandrosterone (DHA), DHA sulphate (DHAS), and 7 alpha-hydroxy DHA (7 alpha DHA), and tumour oestrogen receptor (ER) and progesterone receptor (PR) status were examined in pre, peri-, and postmenopausal women with breast cancer. Androgenic steroids and their metabolites decreased with age in women with breast cancer. In perimenopausal women there was a significant association of PR positive tumours and high androgen levels, whereas in postmenopausal women high androgen levels were associated with ER negative tumours. Survival was significantly related to plasma DHA level and tumour steroid receptor status. Thus, adrenal androgen levels below the group mean were associated with significantly decreased survival in women with postmenopausal receptor-positive tumours, and the association was particularly apparent in those who were axillary node negative. Since the number of patients studied was small these results should be regarded as provisional in nature. Nonetheless, the identification of this subgroup of node negative breast cancer women with reduced survival may be important when considering node negative patients for adjuvant therapy.

[Changes in hypothalamus-pituitary-adrenal (HPA) axis and the deficiency-excess syndrome differentiation on epidemic hemorrhagic fever patients].

UNLABELLED: In order to understand the relationship between the functional changes of hypothalamus-pituitary-adrenal (HPA) axis and the Deficiency-Excess Syndrome Differentiation of traditional Chinese medicine (TCM), the levels of serum cortisol and urinary 17-hydroxy-corticosteroid (U 17-OH) per 24 hours were studied. 171 serum samples and 139 urinary samples were obtained from 87 patients suffering from epidemic hemorrhagic fever (EHF) in various stage. RESULT: The Syndrome displayed as Excess-Heat type accompanied with Blood Stasis in febrile phase of EHF, both the level of serum cortisol and the U 17-OH increased to meet the stress. But the Syndrome converted from the Excess-Heat type to the Cold-Deficiency type in hypotensive and shock phase and the secretion of HPA axis began to reduce. However, in oliguric phase, the Syndrome was Kidney Deficiency complicated with Blood-Heat and Blood Stasis, their U 17-OH lowered significantly (7.53 +/- 3.82 mg/24 h.) in comparing with normal control (P < 0.01), but the level of serum cortisol, on the contrary, raised significantly (1517.96 +/- 421.96 mol/L) in comparing with control (P < 0.01). And in diuretic phase, the Syndrome was the Cold-Deficiency type, the HPA excretion tended to restore gradually but 17-OH maintain at a lower level in serious case. Therefore the change of serum cortisol was closely related with the HPA excretion in all phases of EHF, as well as to the Deficiency-Excess Syndrome Differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Síndrome de Cushing: Estudo comparativo de métodos diagnósticos / Cushing's syndrome: A comparative study of diagnostic methods

Comparamos as respostas dos corticosteróides urinários:17-hidroxicorticosteróides (17-OHCS), 17-cetosteróides (17-KS) e cortisol livre (FC) à supressäo com dexametasona (baixa dose - 2 mg e alta dose - 8mg) em 71 pacientes com síndrome de Cushing (45 com doença de Cushing, 12 com carcinoma adrenal, oito com adenoma adrenocortical e seis com hiperplasia nodular da córtex adrenal). Os pacientes com doença de Cushing e hiperplasia nodular da córtex adrenal näo apresentam supressäo suficiente com 2 mg de dexametasona,porém o fazem com 8 mg. Os tumores adrenais näo demonstram supressäo adequada. A resposta hiperativa dos 17-OHCS, 17-KS e FC ao hormônio adrenocorticotrópico (ACTH) exógeno foi comparada na doença de Cushing. Concluimos que a determinaçäo urinária dos 17-OHCS, 17-KS e FC säo parâmetros diagnósticos úteis, embora a dosagem do FC mostrou ser um índice mais sensível da hiperfunçäo adrenocortical

[Considerations in clinical testing--implications of urinary 17-ketosteroid sulfate and 17-hydroxycorticosteroid measurements for stress research].

With the recent increase in number of patients with stress, the search is continuing for health-indicators that can be used to determine stress reliably and quickly. These indicators rely on subjective evaluations, and the establishment of an objective method of determining stress is necessary. We have developed a method involving the determination of the 17-Ketosteroid sulfates (17-KS-S) which has proved valuable for stress research. By simultaneous measurement of both 17-KS-S and 17-hydroxycorticosteroids (17-OHCS), which have different biological significance, and which originate from the adrenal gland, an organic Yin-Yang evaluation of the adrenocortical function can be made. The two values (mainly the 17-KS-S values) are closely correlated to the biological stress state as evaluated from psychosocial factors. This method should prove to be valuable in the clinic as an objective method of determining stress.

[Primary care considerations--17-ketosteroid sulfate-17-hydroxycorticosteroid method as a clinical stress indicator].

In primary care, the management of stress-related diseases occupies a wide spectrum of prevention and treatment, from holistic health care to final cure, centered on medical health and an organic integration of body, mind, and social parameters. Inquiries are being made at examinations and interviews to obtain information on the health condition of the patient, but, they are inadequate. There is a need for an objective indicator to help in the diagnosis. With the introduction of the Stress Barometer (measurements of 17-ketosteroid sulfates and 17-hydroxy-corticosteroids) it has become possible to obtain critical information on a patient in a very short time. This method allows early detection of stress, depression state and tiredness from work which is not presently possible from blood tests. It then becomes possible to call the patient's attention to these matters and to work at increasing awareness, energy levels, and responses to the conditions that are determined in this manner.

Progression of chronic renal failure on substituting a ketoacid supplement for an amino acid supplement.

Twelve patients with severe chronic renal failure (average initial GFR, 13 mL/min) were monitored for 4 to 23 months while receiving an essential amino acid supplement and were then switched to a ketoacid supplement for 6 to 40 months, while continuously receiving a very low-protein (0.3 g/kg), low-phosphorus (7 to 9 mg/kg) diet. Urinary urea N excretion indicated that actual dietary protein intake averaged 0.46 g/kg. Progression, estimated as the linear regression slope of radioisotopically determined GFR on time, slowed from -0.46 +/- 0.31 (SD) to -0.24 +/- 0.15 mL/min/month (P = 0.029). Serum urea N, creatinine, phosphate, and uric acid rose significantly as GFR fell; blood pressure, plasma lipids, and urinary urea excretion were unchanged. Urinary 17-hydroxy-corticosteroid excretion decreased 18%, but this change was only marginally significant (P = 0.087). There was no change in plasma or urinary cortisol or urinary aldosterone. Viewed in light of previous evidence that progression seldom slows when treatment remains constant, the results suggest that this ketoacid supplement slows progression by approximately half, compared with an essential amino acid supplement, with no change in diet.

[Treatment of climacteric syndrome with new gengnian prescriptions].

It was found by the observations of clinical treatment that the three indexes of epinephrine(E), norepinephrine(NE) and dopamine(D) of urinary catecholamine(CA) increased (P less than 0.001, P less than 0.05 and P less than 0.001) for the climacteric patients who suffered from the deficiency of Yin leading to the hyperactivity of the internal heat of the heart, and the urinary 17-hydroxycorticosteroid (17-OHCS) increased (P less than 0.001) for the patients who suffered from the deficiency of Yin leading to the hyperactivity of the internal heat of the liver. Both the three indexes and urinary 17-OHCS increased for the two groups (P less than 0.01). However, for all the above groups who suffered from the deficiency of Yin leading to the hyperactivity of the internal heat, the NE/E ratio was larger than the normal ratio, which stands for the level of central catecholamine. After the treatment with new Gengnian prescriptions, the clinical symptoms of the patients were improved, and in the meantime urinary CA. 17-OHCS and NE/E were decreased. The total efficiency was 89.2%. The principle of treatment with this prescription may be due to the fact that the level of central catecholamine decreased so that the excessive excitation of sympathetics-adrenocortical system and sympathetics-adrenocortical system was restrained.

[Endocrine function in stomach yin deficiency syndrome (SYDS): research on patients with SYDS following abdominal surgery or severe acute abdominal diseases (II)].

Patients with SYDS following abdominal operation or with severe acute abdominal diseases were observed on changes of the thyroid, adrenal function and digestive hormones. The results showed that the serum concentration of T3 in patients with SYDS decreased by about 50% with the control (P less than 0.001). The concentration of T4 decreased too (P less than 0.001). The rT3 content increased and there were no obvious changes in the content of TSH and T3RUR. The manifestations conformed to "low T3 syndrome" in nonthyroid diseases. The amount of urine 17-KS and 17-OHCS per 24 hours decreased (P less than 0.001 and P less than 0.05 respectively). The serum gastrin level decreased by 60.4% with the control (P less than 0.002) and that of VIP increased (P less than 0.05). The results suggested that the patients had decreased thyroid and adrenal function and the secretion of hormones of digestive tract decreased.

D-glucaric acid excretion in critical care patients--comparison with 6 beta-hydroxycortisol excretion and serum gamma-glutamyltranspeptidase activity and relation to multiple drug therapy.

The incidence of increased drug metabolism activity as a consequence of multiple drug therapy at a surgical intensive care ward has been studied non-invasively by determinations of daily urinary D-glucaric acid (GA) excretion rates. Among 165 randomly selected patients, GA excretion was stimulated in 76 cases (= 46%). Exploratory data analysis showed that increases in GA excretion are primarily due to administration of barbiturates (pentobarbitone, Nembutal), miconazole (Daktar) and, to a lesser extent, neuroleptics. Surprisingly, the large number of simultaneously administered additional drugs failed to increase GA excretion. Urinary 6 beta-hydroxycortisol (6 beta-OHF) and 17-hydroxycorticosteroid (17-OHCS) excretion rates were correlated in 34 patients with GA excretion; patients not receiving known enzyme inducers showed low GA values but high 6 beta-OHF and 17-OHCS values, however, with a ratio of 6 beta-OHF/17-OHCS in the normal range. Patients receiving high dose pentobarbitone treatment failed to exhibit significantly increased 6 beta-OHF and 17-OHCS or 6 beta-OHF/17-OHCS values. Miconazole treatment resulted in a significantly increased ratio of 6 beta-OHF/17-OHCS. gamma-Glutamyltranspeptidase activity in serum showed no correlation with GA excretion (n = 91).

A comparison of electro-acupuncture, transcutaneous electrical nerve stimulation and laser photo-biostimulation on pain relief and glucocorticoid excretion. A case report.

A clinical case report of the comparative effects of electro-acupuncture, Transcutaneous Electrical Nerve Stimulation (TENS) and laser photo-biostimulation on pain relief and 24-hour urinary excretion of 17-hydroxy-corticosteroids (17-OH-CS) following each biostimulation in a patient with a normal pituitary adrenal axis is presented. The excretion of 17-OH-CS after electro-acupuncture was higher than other modalities of treatments while there was no difference in pain relief among different modalities under this particular condition used in this study.