Scalp hair cortisol and testosterone levels in patients with sarcoidosis.

BACKGROUND: Patients with sarcoidosis often experience fatigue and psychological distress, but little is known about the etiology of these conditions. While serum and saliva steroid hormones are used to monitor acute steroid levels, scalp hair analysis is a relatively new method enabling measurement of long-term steroid levels, including hair cortisol reflecting chronic stress. We investigated whether scalp hair cortisol and testosterone levels differ between sarcoidosis patients both with and without fatigue and general population controls. Additionally, we studied if these hormones could serve as objective biomarkers for psychological distress in patients with sarcoidosis. METHODS: We measured hair steroid levels using liquid chromatography-tandem mass spectrometry in glucocorticoid naïve sarcoidosis patients. Patients completed the Perceived Stress Scale, Fatigue Assessment Scale, Hospital Anxiety and Depression Scale and Short Form 36 (SF-36). Hair steroid levels from 293 participants of the population-based Lifelines cohort study served as controls. RESULTS: Thirty-two patients (14 males) were included. Hair cortisol, but not testosterone, concentrations were significantly higher in patients with sarcoidosis than in general population controls (mean 6.6 versus 2.7 pg/mg, p<0.001). No differences were found in hair cortisol and testosterone levels between fatigued and non-fatigued patients with sarcoidosis. Hair cortisol of sarcoidosis patients correlated significantly with anxiety (r = 0.47, p = 0.01), depression (r = 0.46, p = 0.01), and SF-36 mental domain (r = -0.38, p = 0.03), but not with fatigue. CONCLUSIONS: Patients with sarcoidosis have chronically higher levels of the stress hormone cortisol than the normal population, while testosterone levels in hair did not differ. Hair cortisol levels were positively related to subjective measures of psychological distress, but not to fatigue. Our study shows that hair cortisol is a promising non-invasive biomarker for psychological distress in patients with sarcoidosis. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03108547. Registered 31 March 2017, retrospectively registered.

Validation of deuterium and oxygen18 in urine and saliva samples from children using on-line continuous-flow isotope ratio mass spectrometry.

The doubly labelled water method is valuable for measuring energy expenditure in humans. It usually involves blood or urine sampling, which might be difficult in neonates and children with cerebral palsy or other disabilities. We therefore aimed to validate a method making use of saliva samples analyzed by automated thermal conversion elemental analyzer in combination with isotope ratio mass spectrometry (TC-EA/IRMS). The subjects received labelled water orally and urine and saliva samples were collected and analyzed. Deuterium as well as oxygen18 was measured in one single run using a peak jump method. Excellent linearity was found for measurement of enrichments of deuterium (R2 = 0.9999) and oxygen18 (R2 = 0.9999). The intra-assay precision and the inter-assay precision of the measurement of two standards were good for both deuterium and oxygen18. The variation between urine and saliva samples was small (4.83% for deuterium and 2.33% for oxygen18 n = 40). Saliva sampling is to be preferred, therefore, as it can be easily collected and is non-invasive. Moreover, its time of production is almost exactly known. The TC-EA/IRMS method is a good alternative to the more laborious off-line IRMS measurements.

Imaging of glutamate release from the goldfish retinal slice.

A fluorometric procedure to image release of the neurotransmitter glutamate from living retinal slices is described. Patterns of endogenous glutamate efflux were imaged with a cooled CCD camera in goldfish retinal slices as NADH fluorescence produced by a cycling glutamate dehydrogenase (GDH). Basal and potassium evoked glutamate effluxes were strongly localized to the outer and inner plexiform layers, supporting the model that photoreceptors and bipolar cells release glutamate as their prime fast neurotransmitter.

Conditioning of drug-induced immunomodulation in human volunteers: a European collaborative study.

Although several studies on conditioning of the immune system in animals have been published, no comparable data on human research have been available in the past. The present paper presents results of conditioning studies in volunteers performed in two research centres, namely the University of Trier (Germany) and the University of Utrecht (The Netherlands). After administration of a neutral stimulus (conditioned stimulus: CS), subjects were injected with epinephrine (unconditioned stimulus) for three or four days (depending on study). Subcutaneous injection of epinephrine caused a rapid enhancement of the activity of natural killer cells (NKCA) in venous blood, which was chosen as the unconditioned response. On the test trial, when saline instead of epinephrine was injected, the Trier group found a conditional enhancement of NKCA. No changes in NKCA were found in the control subjects, who received saline injections on all days along with the CS. The Utrecht group tried to replicate these results using a slightly different design. After obtaining non-confirmative results, the Utrecht experimenters tried to parallel the experimental settings of the Trier group as closely as possible. However, once again they failed to replicate the results of the Trier group. Possible reasons for the different results obtained in the two research groups are discussed.

Nocturnal hypertension in renal failure, haemodialysis and after renal transplantation.

Diurnal blood pressure variations in 20 patients with advanced renal failure, 20 patients on chronic haemodialysis, and 21 renal transplant recipients were compared with those of matched control groups without renal disease, using 24-h ambulatory blood pressure monitoring. Whereas the blood pressure during the day (from 8 a.m. to 8 p.m.) was roughly the same in the patients compared with their respective control groups, during the night (from 8 p.m. to 8 a.m.) it was substantially higher in all patient groups. The differences between the mean daytime and night-time values were significantly lower in the patients (P less than 0.05 to P less than 0.001). The nocturnal blood pressure decrease may be attenuated or even reversed in renal failure, in haemodialysis and after renal transplantation. In a proportion of these patients, 24-h ambulatory blood pressure monitoring showed an elevated nocturnal blood pressure, which may require some modification of treatment.

[Medical and psychosocial effects of methadone substitution in HIV infected substance-dependent patients]. / Medizinische und psychosoziale Effekte der Methadon-Substitution HIV-infizierter Drogenabhängiger.

After an average observation time of 12 months we can confirm that methadone substitution on an outpatient basis has proved significantly useful for a majority of chronically intravenously opiate-dependent HIV-infected patients of the stages CDC IV or WR 3-6 if methadone is given under controlled conditions, the improvement consisting in an amelioration of certain medical and psychosocial parameters. In 25 out of 30 patients methadone substitution resulted in termination of the previously existing intravenous heroin addiction. In the further course of treatment one of these 25 patients could then be induced to undergo a methadone withdrawal course followed by long-term withdrawal therapy. Since the patients were no longer dependent on heroin, they were no longer compelled to procure it under all circumstances, so that crime and prostitution connected with the pressure to obtain heroin by all means were now superfluous. This provided the most important prerequisites for medical and social care for the patients. The decisive factors determining the effectivity of substitution and hence a successful stabilisation are the integration of the patient in a network of care including the family doctor, outpatient HIV care by a relevant clinic, drug advice centre of AIDS help, and a Public Health Office. This also guarantees that the patients act responsibly in respect of their AIDS infection. In very few patients the permanent success of the treatment was at high risk due to unsatisfactory social care, lack of social security measures, progression of the underlying disease, a too low methadone dosage level, and partnership conflicts.

[Late metastasis of an extragonadal Leydig cell tumor]. / Spät-Metastasierung eines extragonadalen Leydig-Zelltumors.

The case of a 36-year-old patient who underwent extirpation of a Leydig cell tumor of the epididymis is presented. Five years later a retroperitoneal mass was removed, which was found to be a metastatic Leydig cell carcinoma. The literature conrains reports of only 32 cases of metastatic Leydig cell tumors, all of which had originated in the testis and not extragonadally. The symptoms, treatment and prognosis are discussed with reference to the literature.

Can secondary hypertension be identified by twenty-four-hour ambulatory pressure monitoring?

Circadian blood pressure rhythms were examined in subjects exhibiting various forms of secondary and essential hypertension and in normotensive subjects with and without renal disease. Indirect ambulatory blood pressure recordings were performed in 284 subjects for 24 h. In contrast to patients with essential hypertension and to normotensive healthy subjects, the circadian fluctuations of blood pressure were reduced in secondary hypertensives and in normotensive renal patients. In renal hypertensives, these alterations in the diurnal blood pressure variations were dependent on the degree of renal failure. Calculations based on comparisons of the mean sleeping and mean daytime blood pressures identified 89.8% of the essential hypertensives and 72.5% of the patients with secondary hypertension. A large proportion of the patients with secondary hypertension had very high blood pressure levels during sleep, in many cases even exceeding the daytime levels. Thus, 24-h ambulatory blood pressure curves from patients with secondary and essential hypertension can be distinguished from each other. In secondary hypertension, blood pressure monitoring during both day and night is particularly useful for evaluating frequently severe nocturnal hypertension, which may require particular treatment.

Twenty-four-hour blood pressure is not dependent on endogenous circadian rhythm.

The effects of shifted working and sleeping phases on the diurnal blood pressure rhythm were investigated in 15 physically working industrial shift workers at a slowly rotated three-shift system. Ambulatory 24-h blood pressure monitoring was performed during the morning and night shifts. In the two shifts the mean 24-h blood pressure was identical. There were no differences in the blood pressure levels in the sleeping phases or in the working periods between the two 24-h cycles. Diurnal blood pressure fluctuations had equal amplitudes. Corresponding to the lag between the working period there was a phase difference of 8 h between the 24-h blood pressure curves. At this lag, there was a high correlation between the mean hourly blood pressure values (r = 0.683). Twenty-four-hour blood pressure curves during the first and last day of a night shift were nearly equal. Thus the effects of shift rotation on the 24-h blood pressure profile were fully expressed within the first 24 hours. The immediate and complete adaptation of the 24-h blood pressure curve to shifted activity and sleeping phases indicates that activity determines the diurnal blood pressure profile. The blood pressure is largely independent of internal circadian rhythm.

Long-term effects of a complex behavioral treatment of essential hypertension.

A multidimensional behavioral program was developed for the treatment of essential hypertension. Over a course of 6 weeks, 108 patients of a rehabilitation center were treated with this program consisting of health education, self-monitoring of blood pressure, relaxation techniques, and a social skill training in addition to standard medical treatment alone. Blood pressure and other cardiovascular risk factors were monitored for a period of 12 months. Blood pressure levels became normotensive in both groups at the end of the 6-week training program. However, the blood pressure reduction in the behavioral treatment group was achieved with fewer patients taking antihypertensive medication than in the control group. The number of patients taking antihypertensive drugs in the treatment group was 60.2% prior to treatment and 44.4% after treatment; figures for the control group were 68% and 73.8%, respectively (p less than or equal to 0.01). Almost identical data were obtained at the 6- and 23-month follow-up examinations. No consistent changes were observed in weight, smoking, or blood lipids. These results demonstrate beneficial and long-lasting effects of a combined medical and psychologic treatment of essential hypertension as compared to medical treatment alone.

Intracellular calcium in hypertension: effect of treatment with beta-adrenoreceptor blockers.

In 41 essential hypertensive patients, the intraerythrocytic free calcium (aiCa2+) was determined before and after oral treatment with beta-adrenoreceptor blockers (atenolol, metipranolol, and pindolol). The measurements were performed by means of an ion-selective electrode. During the 4 weeks of treatment, the aiCa2+ decreased from 7.4 +/- 2.3 (mean +/- SD) to 4.1 +/- 1.7 mumol/l (p less than 0.001) in the total group of 41 patients. In the patients treated with atenolol (n,15), the aiCa2+ decreased from 7.1 +/- 1.8 to 4.4 +/- 1.7 mumol/l (p less than 0.001); in those treated with metipranolol (n,13), aiCa2+ decreased from 7.4 +/- 2.7 to 4.3 +/- 2.0 mumol/l (p less than 0.001); and in those treated with pindolol (n,13), aiCa2+ decreased from 7.6 +/- 2.4 to 3.8 +/- 1.5 mumol/l (p less than 0.001). In the total group, the mean reduction of the mean blood pressure was 12 mm Hg. In the atenolol subgroup, the blood pressure was reduced by 11 mm Hg, in the metipranolol subgroup by 15 mm Hg, and in the pindolol subgroup by 18 mm Hg. Thus, the reduction of the blood pressure during beta-adrenoreceptor blockade is accompanied by a reduction of the free calcium of the red cells. The calcium lowering effect as the antihypertensive potency is roughly equal among the different beta-adrenoreceptor blockers.

Compliance with salt restriction as a limiting factor in the primary prevention of hypertension.

It is an important but still unresolved question whether reduction of salt intake in the offspring of hypertensives (a high risk group) prevents the development of the disease. Therefore, 178 offspring (14-26 years old) of hypertensives were enrolled in a 2-year pilot trial aimed mainly at a reduction in salt consumption. For the intervention group (n = 99) a behavioural approach was chosen with extensive counselling by experienced dietitians. The controls (n = 79) received no continuous dietary advice. Both groups showed a small decline in sodium intake over time, but the differences between the two groups were not significant. Division into subgroups with and without sodium reduction revealed no differences in blood pressure. We conclude that the inherent resistance to any change of lifestyle among healthy subjects may require new and more comprehensive motivational approaches.

Intracellular sodium and calcium in essential hypertension.

Intracellular sodium and calcium activities were measured by ion-selective electrodes in red blood cells of primary hypertensives and of normotensives with and without a familial disposition to hypertension. Intraerythrocytic sodium activity was markedly elevated in patients and normotensives with a familial disposition to hypertension (15.16 +/- 2.35 mmol/l in hypertensives and 9.74 +/- 1.43 mmol/l in normotensives, respectively, mean value +/- SD) as compared to the corresponding group without such a history (8.35 +/- 2.08 mmol/l in hypertensives and 7.00 +/- 1.38 mmol/l in normotensives). Mean intraerythrocytic calcium activity showed the highest values in patients with hypertension (32.8 +/- 32.5 mumol/l in patients with and 25.3 +/- 19.0 mumol/l in those without a familial disposition to hypertension), whereas in normotensives mean calcium activity was much lower (9.6 +/- 9.7 and 4.8 +/- 4.5 mumol/l, respectively). Our results document that a disturbed intraerythrocytic sodium metabolism is limited to patients with essential hypertension and a familial disposition to hypertension and, to a lesser extent, to normotensives showing a familial disposition to hypertension. Thus, a genetically determined alteration in intracellular sodium can be assumed. Furthermore, the observation of an enhanced intraerythrocytic calcium in some essential hypertensives with and without a familial disposition suggests additional factors, other than sodium, responsible for the disturbed intracellular calcium balance in these patients.

[Factors determining compliance in hypertensive patients]. / Compliance-bestimmende Faktoren bei Hypertonikern.

The influence of various demographic, disease-related and therapeutic factors on compliance has been investigated in 110 patients with hypertension, heart failure or edema. While demographic factors such as age, sex, socioeconomic status, marital status and smoking habits, scarcely influenced drug adherence, duration of therapy showed the greatest compliance-lowering effect. In the 27 hospitalized patients compliance decreased in 3.2 weeks from 92.6% to 75% and in 83 outpatients from 83% to 56% in 17.8 weeks. Totally mean compliance of hospitalized patients was higher (86.9%) than in outpatients (79.7%). The percentage of fully compliant patients was also greater (74%) in hospitalized patients than in outpatients (54.2%). Patients with symptomatic diagnoses complied better than asymptomatic patients: Mean compliance rate was 87% (n = 17) in outpatients with heart failure or edema and 77.3% (n = 66) in hypertensive outpatients. Hypertensives with symptoms due to other diseases also showed a higher compliance (80%) than those with asymptomatic diagnoses (71.1%). New symptoms during therapy and side effects of the antihypertensive treatment decreased the percentage of compliers to 64% and 59% respectively. On the other hand, the severity of hypertension had no effect on drug adherence. Patients with systolic blood pressure values between 140 and less than 180 mm Hg showed an identical compliance (79.8%; n = 47) to those with systolic values greater than 180 mm Hg (79.9% n = 60).