A randomized controlled trial of a cognitive-behavioural group intervention versus waiting-list control for women with uterovaginal agenesis (Mayer-Rokitansky-Küster-Hauser syndrome: MRKH).

BACKGROUND: Uterovaginal agenesis (Mayer-Rokitansky-Küster-Hauser syndrome: MRKH) is a congenital abnormality of the female genital tract, characterized by the non-formation of the vagina and uterus. There is a widespread agreement that MRKH has a lasting negative psychological impact on women with this condition, but as yet little is known about how to conceptualize and manage this. We developed a cognitive-behavioural group treatment (CBT) of MRKH. The aim of the present study was to determine whether this intervention, compared to waiting-list control, improves psychosocial outcomes in women with MRKH. METHODS: After stratifying for age and type of MRKH (simple or complex), 39 women with MRKH were randomized to group CBT (n = 19) or waiting list (n = 20). Outcomes were assessed at pre-treatment, post-treatment (7 weeks) and at 3 months follow-up. The main outcome measure was the Symptom Check-List (SCL-90-R). Other outcomes included impact of event, self-esteem and interpersonal functioning. RESULTS: Participants allocated to group CBT showed significantly reduced psychological symptoms on the SCL-90-R and non-significant improvements on all secondary outcomes at the end of treatment and follow-up, whereas those on the waiting list remained unchanged. CONCLUSIONS: A group CBT intervention improves psychological outcomes in MRKH. This treatment may also be applicable to other gynaecological conditions.

Caries prevalence measured with QLF after treatment with fixed orthodontic appliances: influencing factors.

Caries prevalence on the buccal surfaces of teeth in orthodontic patients was determined with QLF and visual examination immediately after removal of fixed appliances. The number of lesions found by QLF far outnumbered that found by visual examination, but the distribution pattern was similar. 97% of all subjects and on average 30% of the buccal surfaces in a person were affected. On average, in males 40% of surfaces and in females 22% showed white spots (p < 0.01). Caries prevalence was lower (p < 0.01) in incisors and cuspids than in molars and premolars. A positive correlation with caries prevalence was found for the bleeding scores 6 weeks after debonding and lactobacillus counts before debonding. Mutans streptococci counts, age, treatment duration, socioeconomic status and dietary habits showed no correlation with caries prevalence.

Multiple use of soluble metallodendritic materials as catalysts and dyes.

Different sizes of core-functionalized metallodendritic wedges were prepared by anchoring sensor-active arylplatinum(II) sites at the focal point of Fréchet-type polyether dendritic wedges of various generations. The strong color of these metallodendrimers in the presence of SO2 was used to assess the permeability of nanofiltration membranes (molecular weight cut-off of 400 dalton) at ambient pressure. A primary result of these studies is that dendrimers do not have to be exceptionally large for successful retention. Hence, nanofiltration, membrane-capped. immersion vials were developed, which operate as sensor devices when loaded with metallodendrimers with good retention properties. Appropriate substitution of the dye site at the focal point of these metallodendritic wedges by a catalytically active group afforded dendritic catalysts that exhibit essentially the same physical properties (shape, retention) as the corresponding dyefunctionalized dendritic wedges. When this homogeneous catalyst is compartmentalized in membrane-capped vials, a unique and convenient method for its retrieval from product solutions is available. Moreover, such immobilized metallodendritic catalysts can be regenerated and stored for months without losing their activity; this provides access for the development of novel sustainable homogeneous catalysts.

Compulsive checking behavior of quinpirole-sensitized rats as an animal model of Obsessive-Compulsive Disorder(OCD): form and control.

BACKGROUND: A previous report showed that the open field behavior of rats sensitized to the dopamine agonist quinpirole satisfies 5 performance criteria for compulsive checking behavior. In an effort to extend the parallel between the drug-induced phenomenon and human obsessive-compulsive disorder (OCD), the present study investigated whether the checking behavior of quinpirole rats is subject to interruption, which is an attribute characteristic of OCD compulsions. For this purpose, the rat's home-cage was placed into the open field at the beginning or the middle of a 2-hr test. RESULTS: Introduction of the home-cage reduced checking behavior, as rats stayed inside the cage. After 40 min, checking resurfaced, as quinpirole rats exited the home-cage often. An unfamiliar cage had no such effects on quinpirole rats or saline controls. CONCLUSIONS: Checking behavior induced by quinpirole is not irrepressible but can be suspended. Results strengthen the quinpirole preparation as an animal model of OCD compulsive checking.

Selective liquid-phase semihydrogenation of functionalized acetylenes and propargylic alcohols with silica-supported bimetallic palladium-copper catalysts.

Silica-supported, bimetallic palladium-copper catalysts were prepared in solution under mild conditions by reacting lithium di(4-tolyl)cuprate with palladium acetate in the presence of silica particles. Small bimetallic palladium-copper particles were deposited on the silica surface as confirmed with TEM-EDAX and EXAFS. The new material has been applied as catalyst in the liquid-phase semihydrogenation of mono- and disubstituted alkynes and showed high selectivity toward the cis-alkenes. The influence of addition of quinoline or potassium hydroxide to the semihydrogenation reaction mixture and the effects of exposure of the catalyst to air before use have been investigated.

The "Dendritic Effect" in Homogeneous Catalysis with Carbosilane-Supported Arylnickel(II) Catalysts: Observation of Active-Site Proximity Effects in Atom-Transfer Radical Addition.

Advantages of homo- and heterogeneous catalysts are united in metallodendritic molecules where nickel-based catalysts are bound to carbosilane dendrimers. The first direct indication of a "dendritic effect" in the redox catalysis behavior is described: variation of the dendrimer support controls the proximity of the Ni(II) centers, which in turn controls catalytic activity. Catalyst deactivation, by means of Ni(III) formation, can be avoided by a larger separation of the Ni(II) centers (see picture).

Vanadium(IV) and -(V) complexes with O,N-chelating aminophenolate and pyridylalkoxide ligands.

Two different monoanionic O,N-chelating ligand systems, i.e., [OC6H2(CH2NMe2)-2-Me2-4,6]- (1) and [OCMe2([2]-Py)]- (2), have been applied in the synthesis of vanadium(V) complexes. The tertiary amine functionality in 1 caused reduction of the vanadium nucleus to the 4+ oxidation state with either [VOCl3], [V(=NR)Cl3], or [V(=NR)(NEt2)3] (R = Ph, (3a, 5a), R = p-Tol (3b, 5b)), and applying 1 as a reducing agent resulted in the synthesis of the vanadium(IV) complexes [VO(OC6H2(CH2NMe2)-2-Me2-4,6)2] (4) and [V(=NPh)(OC6H2(CH2NMe2)-2-Me2-4,6)2] (6). In the case of [V(=N-p-Tol)(NEt2)(OC6H2(CH2NMe2)-2-Me2-4,6)2] (7b), the reduction was sufficiently slow to allow its characterization by 1H NMR and variable-temperature studies showed it to be a five-coordinate species in solution. Although the reaction of 1 with [V(=N-p-Tol)(O-i-Pr)3] (9b) did not result in reduction of the vanadium nucleus, vanadium(V) compounds could not be isolated. Mixtures of the vanadium(V) (mono)phenolate, [V(=N-p-Tol)(O-i-Pr)2(OC6H2(CH2NMe2)-2-Me2-4,6)] (10), and the vanadium(V) (bis)phenolate, [V(=N-p-Tol)(O-i-Pr)(OC6H2(CH2NMe2)-2-Me2-4,6)2] (11), were obtained. With the pyridylalkoxide 2, no reduction was observed and the vanadium(V) compounds [VOCl2(OCMe2([2]-Py))] (12) and [V(=N-p-Tol)Cl2(OCMe2([2]-Py)] (13) were obtained. 51V NMR showed 7b and 12 to be five-coordinate in solution, whereas for 10, 11, and 13 a coordination number of 6 was found. Compounds 12 and 13 showed decreased activity compared to their nonchelated vanadium(V) analogues when applied as catalysts in ethene polymerization. Two polymorphic forms with a difference in the V-N-C angle of 12.5 degrees have been found for 6. Crystal data: 6.Et2O, triclinic, P1, a = 11.1557(6) A, b = 12.5744(12) A, c = 13.1051(14) A, alpha = 64.244(8) degrees, beta = 70.472(7) degrees, gamma = 87.950(6) degrees, V = 1547(3) A3, Z = 2; 6.C6H6, triclinic, P1, a = 8.6034(3) A, b = 13.3614(4) A, c = 15.1044(5) A, alpha = 98.182(3) degrees, beta = 105.618(2) degrees, gamma = 107.130(2) degrees, V = 1551.00(10) A3, Z = 2; 12, orthorhombic, Pbca, a = 11.8576(12) A, b = 12.6710(13) A, c = 14.722(2) A, V = 2211.9(4) A3, Z = 8.

Characterization of excitatory prostanoid receptors in the human umbilical artery in vitro.

1. 5-HT and the prostanoid TP receptor agonists, U46619 and I-BOP, constricted the human umbilical artery with pEC50 values of 7.3+/-0. 2, 6.7+/-0.1, and 7.3+/-0.2, respectively. The selective TP receptor antagonist, GR32191 (0.1 microM), shifted the concentration-effect curves to U46619 and I-BOP to the right, but had no effect on the response to 5-HT. 2. The natural prostaglandins, PGF2alpha and PGE2, caused concentration-dependent contraction with pEC50 values of 5.2+/-0.2 and 4.9+/-0.2, respectively. PGD2 was a partial agonist with a pEC50 of 5.24+/-0.03. GR32191 (0.1 microM) inhibited the responses to all of these compounds suggesting that they produce contraction by acting at TP receptors. 3. Sulprostone failed to elicit contraction in the human umbilical artery at concentrations up to 4.4 microM suggesting the absence of EP1 and EP3 receptors. Despite this, 17-phenyltrinor PGE2 and GR63799 both induced contraction at concentrations above 1 microM, but the effects were sensitive to GR32191 (0.1 microM). 4. Fluprostenol had no effect on the human umbilical artery at concentrations up to 17 microM suggesting the absence of FP receptors. Cloprostenol was ineffective in two tissues, but caused contraction in one tissue at the highest concentration tested (1.7 microM). However, this response was abolished in the presence of GR32191 (0.1 microM). 5. The effects of four TP receptor antagonists were assessed by global non-linear regression analysis. GR32191, SQ29548, SQ30741, and ICI192605 competitively inhibited responses to U46619 with pKb values of 8.0+/-0.1, 7.6+/-0.1, 7.0+/-0. 2 and 8.1+/-0.1, respectively. 6 These results suggest that the human umbilical artery functionally expresses TP receptors, but not EP1, EP2 or FP receptors.

Reversed phase-high performance liquid chromatographic (RP-HPLC) method to measure migration of semi-volatile compound, vanillin, in ipratropium bromide inhalation solution.

Ipratropium bromide, a bronchodilator, is used as an inhalation solution. Commercial ipratropium bromide solution products are packaged in low-density polyethylene (LDPE) vials, through which semivolatile compounds are reported to migrate. In this article, a specific reversed phase-high performance liquid chromatographic method to assay vanillin, a semivolatile compound, in ipratropium bromide solution is described. The method was validated for a concentration range for vanillin from 30 ng/mL to 1,600 ng/mL. Migration of vanillin was assessed in two commercial preparations, ATROVENT (ipratropium bromide) Inhalation Solution packaged in a secondary foil pouch and a generic ipratropium bromide inhalation solution packaged in a carton. Levels of vanillin detected in ATROVENT after 6 months of storage at 40 degrees C and 75% RH were below the limit of detection (11 ng/mL). Significant migration of vanillin was observed after 1 month in the generic product and reached 165 ng/mL to 999 ng/mL in three months under the same storage conditions. It is concluded that this method can be readily used to measure vanillin in commercial preparations of ipratropium bromide inhalation solution. The results strongly indicate that a protective secondary packaging material is critical in preventing migration of semivolatile compounds. This study result is in agreement with the FDA's recommendation to consider even the secondary packaging components as potential sources of contamination and the use of an overwrap (typically aluminum foil) to decrease the overall permeability.

Function of the hypothalamic-pituitary-adrenal axis in patients with fibromyalgia and low back pain.

OBJECTIVE: We suggested fibromyalgia (FM) is a disorder associated with an altered functioning of the stress-response system. This was concluded from hyperreactive pituitary adrenocorticotropic hormone (ACTH) release in response to corticotropin-releasing hormone (CRH) and to insulin induced hypoglycemia in patients with FM. In this study, we tested the validity and specificity of this observation compared to another painful condition, low back pain. METHODS: We recruited 40 patients with primary FM (F:M 36:4), 28 patients (25:3) with chronic noninflammatory low back pain (LBP), and 14 (12:2) healthy, sedentary controls. A standard 100 microg CRH challenge test was performed with measurement of ACTH and cortisol levels at 9 time points. They were also subjected to an overnight dexamethasone suppression test, followed by injection of synthetic ACTH1-24. At 9 AM, the patients divided in 2 groups, received either 0.025 or 0.100 microg ACTH/kg body weight to test for adrenocortical sensitivity. Basal adrenocortical function was assessed mainly by measurement of 24 h urinary excretion of free cortisol. RESULTS: Compared to the controls, the patients with FM displayed a hyperreactive ACTH release in response to CRH challenge (ANOVA interaction effect p = 0.001). The mean ACTH response of the patients with low back pain appeared enhanced also, but to a significantly lesser extent (p = 0.02 at maximum level) than observed in the patients with FM. The cortisol response was the same in the 3 groups. Following dexamethasone intake there were 2 and 4 nonsuppressors in the FM and LBP groups, respectively. The very low and low dose of exogenous ACTH1-24 evoked a dose and time dependent cortisol response, which, however, was not significantly different between the 3 groups. The 24 h urinary free cortisol levels were significantly lower (p = 0.02) than controls in both patient groups; patients with FM also displayed significantly lower (p < 0.05) basal total plasma cortisol than controls. CONCLUSION: The present data validate and substantiate our preliminary evidence for a dysregulation of the HPA axis in patients with FM, marked by mild hypocortisolemia, hyperreactivity of pituitary ACTH release to CRH, and glucocorticoid feedback resistance. Patients with LBP also display hypocortisolemia, but only a tendency toward the disrupted HPA features observed in the patients with FM. We propose that a reduced containment of the stress-response system by corticosteroid hormones is associated with the symptoms of FM.

Glucocorticoid receptors, fibromyalgia and low back pain.

Recently, fibromyalgia (FMS) was shown to be a disorder associated with an altered functioning of the stress response system. FMS patients display a hyperreactive pituitary adrenocorticotropic hormone (ACTH) release in response to corticotropin-releasing hormone (CRH) and to insulin-induced hypoglycemia. We suggested that negative feedback of cortisol could be deranged. Therefore we investigated the properties and function of the glucocorticoid receptors (GR) in FMS patients and compared the results with those of healthy persons and patients with chronic low back pain (LBP a localized pain condition). Forty primary FMS patients (F:M = 36:4), 28 LBP patients (25:3) and 14 (12:2) healthy, sedentary control persons were recruited for the study. Urinary free cortisol excretion in FMS and LBP patients was lower compared to controls. Only FMS patients displayed lower CBG and basal serum cortisol concentrations when compared to controls. However, plasma free cortisol concentrations were similar in the three groups. There was no difference in the number of GR per cell among the three groups (FMS: 6498 +/- 252, LBP: 6625 +/- 284, controls: 6576 +/- 304), but the dissociation constant (Kd) of the FMS (14.5 +/- 0.9 nmol/l) and LBP (14.7 +/- 1.3 nmol/l) subjects was significantly higher than that of the controls (10.9 +/- 0.8 nmol/l) (p < .05). The maximal stimulation of the lymphocytes, as measured by the maximal thymidine incorporation (in the absence of cortisol) in the FMS group was approximately 1.5 times higher (p < .05) than in the control or LBP group. The ED50 (the cortisol concentration giving 50% inhibition of the thymidine incorporation), however, was identical in all three groups. We conclude that FMS patients have a mild hypocortisolemia, increased cortisol feedback resistance in combination probably with a reduced CRH synthesis or release in the hypothalamus. The role of the GR and mineralocorticoid receptor (MR) in the CRH regulation in the FMS patients remains to be solved.

Lack of correlation between the mean tender point score and self-reported pain in fibromyalgia.

OBJECTIVES: To study the validity and nature of self-assessed symptoms among patients with fibromyalgia syndrome (FMS) and to compare our data with findings reported in the US. To determine whether tender point scores correlate with self-reported pain and other symptoms and to study the influence of disease duration. METHODS: Tender point scores were assessed in 113 consecutive patients with FMS. All patients completed 2 self-assessment questionnaires (an extended Campbell list, the Enschede Fibromyalgia Questionnaire, and the Dutch Arthritis Impact Measurement Scales). RESULTS: The self-assessed symptoms of the Dutch FMS patients seem to be valid and are comparable with those of American patients. No association between disease duration and number of self-reported symptoms was found. An association between self-reported pain and mean tender point score was lacking for patients with disease of shorter duration and was weak for patients with disease of longer duration. CONCLUSIONS: The use of a self-report questionnaire for patients with FMS is feasible and appears to be valid. Tender point scores and self-reported pain represent very different aspects of pain in FMS.

Analysis of a large family with the second type of autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder A mutation in at least three different genes can cause the disease. A mutation in the first gene, the PKD1 gene, which has been identified on chromosome 16p13.3, accounts for ADPKD in approximately 86% of the families with this disorder. In the majority of the other ADPKD families the disease is caused by a mutation in a second gene, the PKD2 gene. This gene has been mapped to chromosome 4q21-22, but has not yet been identified. In a few families ADPKD is not caused by a mutation in either the PKD1 or the PKD2 gene. The locus for a possible third gene has not yet been determined. Now that haplotype analysis with polymorphic markers at the ADPKD1 and ADPKD2 loci is possible, we can easily distinguish between both forms of ADPKD. We describe a large Dutch family in which ADPKD is linked to chromosome 4. Compared with ADPKD1 families, the disease in this family tends to run a milder course, as has been described previously for other ADPKD2 families.

A 1-year follow-up study on leakage of four root canal sealers at different thicknesses.

Determination of leakage using a fluid transport model allows measurement of leakage in a longitudinal manner. Leakage of four sealers at three different thicknesses in 225 bovine root sections, after storage in water for 1 year, was measured again using the same methodology. The change in seal over time for each sealer was observed. The results after the second measurement showed that every sealer produced the best seal when the sealer layer was the thinnest. AH26, Ketac-Endo and Tubli-Seal showed a reduction in leakage over time and gave significantly less leakage than Sealapex (P<0.005). Sealapex showed significantly more leakage after storing in water for 1 year (P<0.005). Therefore, the long-lasting seal of sealer may, among other influencing factors, depend on the layer thickness and the solubility of the material.

Pituitary release of growth hormone and prolactin in the primary fibromyalgia syndrome.

OBJECTIVE: Previously, we demonstrated hyperreactive adrenocorticotropic hormone (ACTH) release in patients with primary fibromyalgia syndrome (primary FMS). We investigated the pituitary release of growth hormone (GH) and prolactin (PRL) in search of further disturbances in neuroendocrine reactivity possibly associated with the pathophysiology of primary FMS. METHODS: Ten female patients with primary FMS fulfilling the 1981 Yunus criteria and 10 matched, healthy and sedentary controls were subjected to an insulin induced hypoglycemia test; samples for measurement of glucose, GH and PRL were taken at intervals. RESULTS: Compared to the controls, the patients with primary FMS displayed significantly lower basal GH levels, whereas their basal PRL levels were slightly, though significantly, higher (respectively p = 0.021 and p = 0.041). Following hypoglycemia, there was a marked, statistically highly significant (p = 0.001), hyperreactivity of the GH response in patients with primary FMS. The PRL response showed wide interindividual variation and did not differ between patients and controls. CONCLUSION: Our findings indicate that fibromyalgia, along with ACTH hyperreactivity, also exhibits a distinct disturbance in the GH-somatomedin C axis. With regard to PRL, the variation in individual responses limits conclusions. The hyperreactive response patterns of GH and ACTH previously suggest a common origin, which might be related to a subtle glucocorticoid deficiency.

Chromosome 4 localization of a second gene for autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder. A gene defect located on the short arm of chromosome 16 is responsible for the disease in roughly 86% of affected European families. Using highly polymorphic microsatellite DNA markers, we have assigned a second gene for ADPKD to chromosome 4. In eight families with clear evidence against linkage to chromosome 16 markers, linkage analysis with the markers D4S231 and D4S423, demonstrated a multipoint lod score of 22.42.

Dental cast study of adult patients with untreated unilateral cleft lip or cleft lip and palate in indonesia compared with surgically treated patients in The Netherlands.

To determine differences in maxillary and dentoalveolar relationships between untreated and treated patients having unilateral clefts of the lip and alveolus (UCLA) or lip and palate (UCLP), dental cast assessments were done on 70 untreated adult Indonesian patients (UCLA-I, UCLP-I) and 67 Dutch patients, surgically treated in infancy (UCLA-D, UCLP-D). The Indonesian group consisted of 44 UCLA-I and 26 UCLP-I patients, and the Dutch group of 24 UCLA-D and 43 UCLP-D patients. In the UCLA-I patients, deformities occurred in that part of the dentoalveolar complex that surrounds the cleft. Lip repair in the UCLA-D group more frequently caused deformities in the incisor and buccal areas on the cleft side. In the UCLP-I patients, deformities were present in the incisor and cuspid areas on the cleft side. The buccal segments showed collapse both on the cleft and noncleft sides. Lip and palate repair in the UCLP-D group caused significantly more deformities in the incisor, cuspid, and buccal areas up to the level of the first molars, both on the cleft and noncleft sides. Surgical treatment seems to cause maxillary and dentoalveolar deformities up to the first molars more frequently, but these are not as pronounced as one would expect: following the practiced surgical regimen, the deformities were usually mild. Negative effects of surgical intervention seem to be antagonized by the restored integrity of the lip and palate leading to orientation of maxillary parts and correction of tongue position, which in turn has a molding effect on the maxilla and mandible.

The reappearance of eggs in faeces of horses after treatment with ivermectin.

The reappearance of nematode eggs in faeces after ivermectin treatment was studied in 104 horses on 10 farms during the stabling period. Faecal samples were taken at weekly intervals. Sampling was discontinued when the mean egg output per farm was > 10% of the pre-treatment egg output. This point was reached after 63 days, when the mean output of eggs had decreased to 70.3%. Before treatment, 95.9% of the cultured larvae were of the cyathostome type, the others belonged to Gyalocephalus capitatus, Strongylus vulgaris, S. edentatus, Oesophagodontus/Poteriostomum spp., Triodontophorus spp. and Trichostrongylus axei. After treatment, the cultures nearly always produced 100% cyathostome larvae, although occasionally low numbers (< 1%) of larvae of large strongyles (mainly S. edentatus, rarely S. vulgaris and Oesophagodontus spp.) and T. axei were seen.

Altered reactivity of the hypothalamic-pituitary-adrenal axis in the primary fibromyalgia syndrome.

The reactivity of the hypothalamic-pituitary-adrenal (HPA) axis was investigated in 10 female patients fulfilling the Yunus criteria for the primary fibromyalgia syndrome (PFS) and in 10 matched, healthy and sedentary controls. The 2 groups were subjected to a dexamethasone suppression (DXM) test, a corticotropin-releasing hormone (CRH) test and an insulin induced hypoglycemia (IH) test. In the DXM test there was no escape from suppression in patients or controls. The CRH and the IH tests showed a markedly enhanced, and statistically significant, adrenocorticotropic hormone (ACTH) release in patients with PFS versus controls, while the cortisol response in both groups was not different. Our data suggest that fibromyalgia is related to a neuroendocrine disorder characterized by hyperreactive pituitary ACTH release and a relative adrenal hyporesponsiveness. This HPA response pattern is unique and contrasts to the hypercortisolemic responses observed in affective disorders, e.g., depression, which like PFS, are often thought to be precipitated by chronic stress. Our findings seem to indicate a relative adrenal insufficiency in PFS, which might serve clinically as an explanation for the reduced aerobic capacity and impaired muscle performance these patients display.

Physiological effects of exhaustive physical exercise in primary fibromyalgia syndrome (PFS): is PFS a disorder of neuroendocrine reactivity?

The influence of maximum exercise has been studied in 10 patients with primary fibromyalgia syndrome (PFS) and 10 healthy sedentary control persons. The exercise consisted of a bicycle ergometertest and a steptest, both till exhaustion. In both tests, the mean maximum workload of the PFS patients was lower than that of the controls. Significantly lower values of serum creatinekinase, myoglobin, cortisol, epinephrine and norepinephrine were found in PFS patients. A striking finding was a lower heart rate in PFS patients compared to the controls under the same workload. The lower (nor)epinephrine concentration together with the lower heart rate suggests a disturbance of the sympathetic activity in PFS patients. The preliminary conclusion is that there is a disturbed reactivity of the sympathetic system as well as of the HPA axis in PFS.