Determinants of radiographic progression in early psoriatic arthritis: insights from a real-world cohort.

OBJECTIVE: Persistent articular inflammation in psoriatic arthritis (PsA) is associated with radiographic damage. Despite advances in diagnosis and therapy, radiographic structural damage remains prevalent in PsA. To elucidate this topic, we studied which baseline clinical characteristics determine radiographic progression. METHODS: For this analysis, data were used from DEPAR (Dutch South West Psoriatic Arthritis) Study, a real-world cohort of patients with newly diagnosed PsA. Radiographic changes were assessed using the modified Total Sharp/van der Heijde Score (mTSS) for PsA. Univariable-multivariable mixed-effects negative binomial regression analysis was applied to define baseline predictors for radiographic progression over time. RESULTS: The study included 476 patients with early PsA with 1660 hand and feet radiographs from four different time points (baseline, first, second and third year). The progressive group (n=71) had a higher mTSS compared with the non-progressive group (n=405) at diagnosis (17 (3-36) vs 0 (0-1)). A comparison of the two groups revealed that the progressive group had significantly older (59 (12) vs 49 (13)) and a higher rate of the presence of swollen joints (93% vs 78%) at diagnosis. Multivariable analysis identified age (incidence rate ratio (IRR)=1.10, p=0.000), sex (female) (IRR=0.48, p=0.043) and baseline mTSS (IRR=1.11, p=0.000) as significant determinants of radiographic change over time. For the progressive subset, additionally, the multivariable analysis highlighted baseline Disease Activity in PSoriatic Arthritis (IRR=1.05, p=0.006) and swollen joint count (IRR=1.07, p=0.034) as predictors. CONCLUSIONS: According to this real-world cohort, patients with early PsA exhibit minimal radiographic progression under current treatment protocols. This study indicates that while old age and initial radiographic damage predict progression, female sex confers a protective effect on it. Furthermore, disease activity score and swollen joints emerged as predictors for radiographic changes during the follow-up in progressive patients.

Three-dimensional printed customized versus conventional plaster brace for trapeziometacarpal osteoarthritis: a randomized controlled crossover trial.

We investigated the non-operative management of trapeziometacarpal osteoarthritis with a three-dimensional (3-D) printed patient-customized brace compared with a conventional plaster brace. Fifty-two patients with symptomatic trapeziometacarpal osteoarthritis were enrolled in a 9-week crossover study, which was designed as a randomized controlled trial of two periods of 4-week brace therapies. The primary outcome was patient satisfaction measured with the Dutch version of the Quebec User Evaluation of Satisfaction with Assistive Technology questionnaire survey. Secondary outcomes included pain, patient-reported function, functional hand strength measured by pinch and grip strength, and compliance assessed through a daily log of self-reported brace usage. The 3-D printed patient-customized brace had higher patient satisfaction and compliance than the conventional plaster brace. Patients preferred the 3-D printed customized brace (93%) rather than the conventional plaster brace (7%). This suggests that the 3-D printed patient-customized brace is effective in the non-operative management of trapeziometacarpal osteoarthritis.Level of evidence: I.

Paternal inflammatory arthritis is associated with a higher risk of miscarriage: results of a large multicentre study (iFAME-Fertility).

OBJECTIVES: Paternal preconception health is recognized as an important contributor to pregnancy outcomes. Nonetheless, pregnancy outcomes of partners of men with inflammatory arthritis (IA) have never been studied. Our objective was to describe the pregnancy outcomes of partners of men diagnosed with IA. METHODS: We performed a multicentre cross-sectional retrospective study conducted in the Netherlands. Men with IA who were over 40 years old that reported at least one positive pregnancy test were included. To analyse the impact of IA on pregnancy outcomes, pregnancies were classified into two groups: pregnancies conceived after the diagnosis of IA and before the diagnosis of IA. RESULTS: In total, 408 male participants diagnosed with IA reported 897 singleton pregnancies that resulted in 794 live births. Pregnancies conceived after the diagnosis of IA had higher rate of miscarriage (12.27 vs 7.53%, P = <0.05). This increased risk was still present after adjusting for confounders [OR 2.03 (95% CI 1.12, 3.69) P = 0.015]. CONCLUSIONS: This is the largest study to describe the pregnancy outcomes of partners of men diagnosed with IA and the first to demonstrate that paternal IA is associated with a higher risk of miscarriage. Notwithstanding, the overall rate of miscarriage reported in our study could be comparable to previously reported population estimates.

Impaired fertility in men diagnosed with inflammatory arthritis: results of a large multicentre study (iFAME-Fertility).

OBJECTIVES: The impact of inflammatory arthritis (IA) on male fertility remains unexplored. Our objective was to evaluate the impact of IA on several male fertility outcomes; fertility rate (number of biological children per man), family planning, childlessness and fertility problems. METHODS: We performed a multicentre cross-sectional study (iFAME-Fertility). Men with IA 40 years or older who indicated that their family size was complete were invited to participate. Participants completed a questionnaire that included demographic, medical and fertility-related questions. To analyse the impact of IA on fertility rate, patients were divided into groups according to the age at the time of their diagnosis: ≤30 years (before the peak of reproductive age), between 31 and 40 years (during the peak) and ≥41 years (after the peak). RESULTS: In total 628 participants diagnosed with IA were included. Men diagnosed ≤30 years had a lower mean number of children (1.32 (SD 1.14)) than men diagnosed between 31 and 40 years (1.60 (SD 1.35)) and men diagnosed ≥41 years (1.88 (SD 1.14)).This was statistically significant (p=0.0004).The percentages of men diagnosed ≤30 and 31-40 years who were involuntary childless (12.03% vs 10.34% vs 3.98%, p=0.001) and who reported having received medical evaluations for fertility problems (20.61%, 20.69% and 11.36%, p=0.027) were statistically significant higher than men diagnosed ≥41 years. CONCLUSIONS: This is the first study that shows that IA can impair male fertility. Men diagnosed with IA before and during the peak of reproductive age had a lower fertility rate, higher childlessness rate and more fertility problems. Increased awareness and more research into the causes behind this association are urgently needed.

Thyrotropin secretion in healthy subjects is robust and independent of age and gender, and only weakly dependent on body mass index.

CONTEXT: Studies of the influence of sex, age, and body weight on TSH secretion are not unanimous. Most reports are based on a single TSH measurement; studies using frequent blood sampling are scarce and include a limited number of selected subjects. OBJECTIVE: The goal was to investigate TSH dynamics in 117 healthy adults. METHODS: TSH was measured by a sensitive immunofluorometric assay. Secretion parameters were quantified by automated deconvolution, approximate entropy [ApEn], spikiness, and diurnal properties. RESULTS: Mean age was 43 years (range, 22-77 y). Mean body mass index (BMI) was 26.8 kg/m(2) (range, 18.3-39.4 kg/m(2)). Daily TSH secretion was 45.4 mU/L (range, 8.0-207 mU/L). There were no sex differences in secretion parameters, including pulse frequency; basal, pulsatile, and total secretion; pulse mode; half life; pulse regularity; ApEn; spikiness; and nycthemeral properties. BMI was positively related to basal secretion. Total secretion correlated negatively with free T4 (R = 0.225; P = .018). The onset of the nocturnal surge was delayed by increasing BMI and advanced by increasing age. ApEn and spikiness correlated positively with age, especially in men. The 9 am sample correlated strongly with the total 24-hour secretion, explaining two-thirds of the variability. CONCLUSION: This study shows that the 24-hour TSH secretion in healthy volunteers is stable and robust and not influenced by sex, BMI, and age. ApEn in the elderly, especially men, is increased, pointing to a less tight feedback control. Furthermore, aging is associated with advance shifting of the TSH rhythm, which is a phenomenon also observed in other biological rhythms.

Discovery of a novel activator of 5-lipoxygenase from an anacardic acid derived compound collection.

Lipoxygenases (LOXs) and cyclooxygenases (COXs) metabolize poly-unsaturated fatty acids into inflammatory signaling molecules. Modulation of the activity of these enzymes may provide new approaches for therapy of inflammatory diseases. In this study, we screened novel anacardic acid derivatives as modulators of human 5-LOX and COX-2 activity. Interestingly, a novel salicylate derivative 23a was identified as a surprisingly potent activator of human 5-LOX. This compound showed both non-competitive activation towards the human 5-LOX activator adenosine triphosphate (ATP) and non-essential mixed type activation against the substrate linoleic acid, while having no effect on the conversion of the substrate arachidonic acid. The kinetic analysis demonstrated a non-essential activation of the linoleic acid conversion with a KA of 8.65 µM, αKA of 0.38µM and a ß value of 1.76. It is also of interest that a comparable derivative 23d showed a mixed type inhibition for linoleic acid conversion. These observations indicate the presence of an allosteric binding site in human 5-LOX distinct from the ATP binding site. The activatory and inhibitory behavior of 23a and 23d on the conversion of linoleic compared to arachidonic acid are rationalized by docking studies, which suggest that the activator 23a stabilizes linoleic acid binding, whereas the larger inhibitor 23d blocks the enzyme active site.

A systematic review of the effects of e-health on chronically ill patients.

AIMS AND OBJECTIVES: We aimed to investigate whether e-health is equal to or better than usual face-to-face care with regard to outcomes on health, quality of life, patient satisfaction and costs. Therefore, we systematically reviewed the literature on e-health in chronically ill patients compared with or as an addition to usual care. BACKGROUND: Interactive websites on internet are increasingly used to inform and treat patients. This type of contact between patients and health care providers, which is called e-health, is easily accessible and particularly interesting for chronically ill patients. DESIGN: A systematic review. METHODS: We searched the databases PubMed, CINAHL, the Cochrane Database of systematic reviews, DARE and CENTRAL for articles published between January 2000-July 2009. RESULTS: The search strategy yielded in total 695 possibly relevant references, which resulted in 12 RCTs after application of the in- and exclusion criteria. Most of the studies were well designed according to the Cochrane criteria for RCTs. The studies are divided into e-health vs. usual care and e-health as addition to usual care. e-Health consisted of monitoring, treatment instructions, self-management training and general information and communication between patient and caregiver. Most of the studies showed small to moderate positive effects on health outcomes. Cost-effectiveness, quality of life and patient satisfaction were rarely investigated in the included studies. CONCLUSIONS: e-Health interventions for chronically ill patients, offered instead of usual care or in addition to usual care, lead to small to moderate positive effects on primary health outcomes. However, the evidence was not fully convincing, because of the limited number of studies available and the methodological limitations. Further research is needed to confirm the cost-effectiveness of e-health interventions for patients with chronic diseases. RELEVANCE TO CLINICAL PRACTICE: e-Health is a promising tool for treatment and self-management training of chronically ill patients.

Altered multihormone synchrony in obese patients with polycystic ovary syndrome.

Luteinizing hormone (LH) concentrations and pulsatility are increased in obese women with polycystic ovary syndrome (PCOS). In addition, patients have hyperandrogenemia and insulin resistance. The mechanisms involved in aberrant hormone regulation in PCOS are still unclear. We investigated 15 obese PCOS women with a body mass index between 30 and 54 kg/m(2) and 9 healthy obese controls (body mass index, 31-60 kg/m(2)) with regular menstrual cycles. Subjects underwent 24-hour blood sampling at 10-minute intervals for later measurements of LH, leptin, testosterone, and insulin concentrations. Data were analyzed with a new deconvolution program, approximate entropy (and bivariate approximate entropy), and a cross-correlation network. Patients had increased LH pulse frequency and more than 2-fold greater daily LH secretion, with diminished pattern regularity. Testosterone secretion was increased 2-fold, but pattern regularity was similar to that in controls. In the network construct, insulin was correlated positively with LH, whereas leptin and testosterone were correlated negatively with LH. Bivariate synchrony of LH with insulin was decreased. Short-term caloric restriction paradoxically increased LH secretion by 1.5-fold and pattern irregularity, and reduced interpulse variability. Testosterone secretion and fasting concentrations of estradiol and sex hormone-binding globulin levels remained unchanged. Correlations between LH and insulin, leptin, and calculated free testosterone decreased. This study demonstrates marked alterations in the control of LH secretion in PCOS in the fed and calorie-restricted states. The ensemble results point to abnormal feedback control of not only the GnRH-gonadotrope complex, but also LH's relationships with leptin, insulin, and testosterone.

Cortisol production rate is similarly elevated in obese women with or without the polycystic ovary syndrome.

CONTEXT: The pituitary-adrenal axis in obesity and polycystic ovary syndrome (PCOS) is marked by increased urinary excretion of cortisol and its metabolites. It is not as yet clear whether the increased cortisol production in PCOS is related to obesity per se. INTERVENTION AND METHODS: We investigated 15 obese PCOS women with a body mass index of 30-54 kg/m(2) and 15 healthy obese controls (body mass index 31-60 kg/m(2)) with a regular menstrual cycle. Patients and control women underwent 24-h blood sampling at 20-min intervals. Cortisol concentrations were measured with a sensitive assay. Data were analyzed with a new deconvolution program, approximate entropy, and cosinor regression. OUTCOME: Basal, pulsatile, and total cortisol production expressed per liter distribution volume, per square meter body surface, and as absolute amount per 24 h was similar in PCOS patients and matched healthy control women. In addition, the regularity of cortisol secretion and the diurnal properties were identical. Compared with 10 lean control women, mean cortisol production per liter distribution volume was similar in the three groups, but the total 24-h cortisol production was increased in obese control women and PCOS women. CONCLUSION: This study demonstrates equally increased cortisol production in PCOS women and obese healthy control women.

The digital eczema centre utrecht.

The University Medical Centre Utrecht (UMC Utrecht) has developed an eczema portal that combines e-consulting, monitoring and self-management training by a dermatology nurse online for patients and parents of young children with atopic dermatitis (AD). Patient satisfaction with the portal was high. It could be extended to become a Digital Eczema Centre for multidisciplinary collaboration between health-care providers from different locations and the patient. Before starting the construction of the Digital Eczema Centre, the feasibility was examined by carrying out a business case analysis. The purposes, strength and weaknesses showed that the Digital Eczema Centre offered opportunities to improve care for patients with AD. The financial analysis resulted in a medium/best case scenario with a positive result of euro50-240,000 over a period of five years. We expect that the Digital Eczema Centre will increase the accessibility and quality of care. The web-based patient record and the digital chain-of-care promote the involvement of patients, parents and multidisciplinary teams as well as the continuity and coordination of care.

Sensitivity and specificity of pulse detection using a new deconvolution method.

Quantifying pulsatile secretion from serial hormone concentration measurements (deconvolution analysis) requires automated, objective, and accurate detection of pulse times to ensure valid estimation of secretion and elimination parameters. Lack of validated pulse identification constitutes a major deficiency in the deconvolution field, because individual pulse size and number reflect regulated processes that are critical for the function and response of secretory glands. To evaluate deconvolution pulse detection accuracy, four empirical models of true-positive markers of pituitary (LH) pulses were used. 1) Sprague-Dawley rats had recordings of hypothalamic arcuate nucleus multiunit electrical activity, 2) ovariectomized ewes underwent sampling of hypothalamo-pituitary gonadotropin-releasing hormone (GnRH pulses), 3) healthy young men were infused with trains of biosynthetic LH pulses after GnRH receptor blockade, and 4) computer simulations of pulsatile LH profiles were constructed. Outcomes comprised sensitivity, specificity, and receiver-operating characteristic curves. Sensitivity and specificity were 0.93 and 0.97, respectively, for combined empirical data in the rat, sheep, and human (n = 156 pulses) and 0.94 and 0.92, respectively, for computer simulations (n = 1,632 pulses). For simulated data, pulse-set selection by the Akaike information criterion yielded slightly higher sensitivity than by the Bayesian information criterion, and the reverse was true for specificity. False-positive errors occurred primarily at low-pulse amplitude, and false-negative errors occurred principally with close pulse proximity. Random variability (noise), sparse sampling, and rapid pulse frequency reduced pulse detection sensitivity more than specificity. We conclude that an objective automated pulse detection deconvolution procedure has high sensitivity and specificity, thus offering a platform for quantitative neuroendocrine analyses.

Disordered and increased adrenocorticotropin secretion with diminished adrenocorticotropin potency in obese in premenopausal women.

CONTEXT: The pituitary-adrenal ensemble of obese humans is marked by increased urinary excretion of cortisol and its metabolites in the face of normal circulating cortisol levels. For better understanding of the (patho) physiological meaning of these changes, the mechanistic underpinnings need to be clarified. INTERVENTION AND METHODS: We investigated 17 obese women [body mass index (BMI) 30-39.4 kg/m(2)] and 14 normal women (BMI, 18.3-24.8 kg/m(2)) who underwent 24-h blood sampling at 10-min intervals, and plasma ACTH and cortisol concentrations were measured with sensitive assays. Data were analyzed with a new deconvolution program, approximate entropy (ApEn) analyses, and cosinor regression. OUTCOME: ACTH and cortisol production rates were higher in obese women than in controls and correlated with BMI. Secretion of ACTH correlated with leptin (R = 0.63; P = 0.0001) and insulin (R = 0.67; P = 0.0001). ACTH ApEn and forward ACTH-cortisol cross-ApEn were diminished in obese women. The half-maximal effective concentration (ED(50)) of ACTH pulses vs. cortisol pulses was higher in obese women (38.3 +/- 4.9 vs. 25.1 +/- 3.7 ng/liter; P = 0.03), indicating decreased potency of ACTH. The diurnal properties of ACTH and cortisol secretion were unchanged in obese females. CONCLUSION: Obese women exhibit enhanced ACTH and cortisol 24-h production compared with lean controls. The amplified ACTH drive is accompanied by decreased secretory regularity and diminished forward coupling between ACTH and cortisol. In addition, the potency of ACTH is decreased in obesity.

Fungal disease of the Western hemisphere: a patient with coccidioidomycosis.

We report the case of a 58 year old male patient with nonproductive coughing, fever, vomiting and loss of appetite, beginning at the moment that he returned back home from a 2 week holiday in California. His symptoms were accompanied by increased inflammatory markers in his blood (leucocytosis, high CRP) and pulmonary sequelae, becoming more prominent shortly after admission. Eventually, the final diagnosis of coccidioidomycosis was made by histopathology and confirmed by serology. Coccidioidomycosis is a rare infectious disease. However, the incidence in the endemic areas of this fungal infection is increasing and the population travelling towards its specific endemic regions in the United States and Southern America is considerably growing. Clinicians facing patients with pulmonary infection with the appropriate travel history and persistent pulmonary or systemic infection (with or without eosinophilia) should be alert to the possibility of coccidioidomycosis. Therefore, we present an up to date overview of the epidemiology, microbiology, clinical features, diagnosis and treatment of patients with coccidioidomycosis.

Bromocriptine reduces augmented thyrotropin secretion in obese premenopausal women.

CONTEXT: Diurnal TSH secretion is enhanced in obese premenopausal women. Dopamine inhibits TSH secretion through activation of dopamine D(2) receptors (D(2)R). Dopamine D(2)R availability in the brain is reduced in obese humans in proportion to body adiposity. We hypothesized that deficient dopamine D(2)R signaling is involved in the enhanced TSH secretion associated with obesity. OBJECTIVE: The effect of short-term bromocriptine treatment on spontaneous TSH secretion in obese women was studied while body weight and caloric intake remained constant. DESIGN AND SETTING: We conducted a prospective, fixed-order, crossover study in a Clinical Research Center. PARTICIPANTS: Seventeen obese women (body mass index, 33.2 +/- 0.6 kg/m(2)) were studied twice in the early follicular phase of their menstrual cycle. INTERVENTION: Subjects were treated for 8 d with placebo and bromocriptine. MAIN OUTCOME MEASURE(S): Blood was collected for 24 h at 10-min intervals, and TSH and leptin were analyzed with deconvolution and correlation techniques, approximate entropy, and cosine regression. RESULTS: Bromocriptine reduced 24-h TSH secretion (placebo, 29.8 +/- 4.6 mU/liter . 24 h, vs. bromocriptine, 22.4 +/- 3.7 mU/liter . 24 h; P = 0.001), whereas free T(4) and total T(3) concentrations did not change. Bromocriptine administration reduced the mesor and amplitude of the 24-h rhythm without resetting the phase. The regularity of the subordinate TSH pattern and synchrony between leptin and TSH were unaffected by bromocriptine. CONCLUSION: Activation of dopamine D(2)R by bromocriptine reverses enhanced diurnal TSH secretion in obese women. Thus, reduced dopaminergic neuronal signaling might be involved in the perturbation of the thyrotrope hormonal axis in obese premenopausal women.

Pituitary-hormone secretion by thyrotropinomas.

Hormone secretion by somatotropinomas, corticotropinomas and prolactinomas exhibits increased pulse frequency, basal and pulsatile secretion, accompanied by greater disorderliness. Increased concentrations of growth hormone (GH) or prolactin (PRL) are observed in about 30% of thyrotropinomas leading to acromegaly or disturbed sexual functions beyond thyrotropin (TSH)-induced hyperthyroidism. Regulation of non-TSH pituitary hormones in this context is not well understood. We there therefore evaluated TSH, GH and PRL secretion in 6 patients with up-to-date analytical and mathematical tools by 24-h blood sampling at 10-min intervals in a clinical research laboratory. The profiles were analyzed with a new deconvolution method, approximate entropy, cross-approximate entropy, cross-correlation and cosinor regression. TSH burst frequency and basal and pulsatile secretion were increased in patients compared with controls. TSH secretion patterns in patients were more irregular, but the diurnal rhythm was preserved at a higher mean with a 2.5 h phase delay. Although only one patient had clinical acromegaly, GH secretion and IGF-I levels were increased in two other patients and all three had a significant cross-correlation between the GH and TSH. PRL secretion was increased in one patient, but all patients had a significant cross-correlation with TSH and showed decreased PRL regularity. Cross-ApEn synchrony between TSH and GH did not differ between patients and controls, but TSH and PRL synchrony was reduced in patients. We conclude that TSH secretion by thyrotropinomas shares many characteristics of other pituitary hormone-secreting adenomas. In addition, abnormalities in GH and PRL secretion exist ranging from decreased (joint) regularity to overt hypersecretion, although not always clinically obvious, suggesting tumoral transformation of thyrotrope lineage cells.

Effects of continuous versus intermittent exercise, obesity, and gender on growth hormone secretion.

CONTEXT: Obesity attenuates spontaneous GH secretion and the GH response to exercise. Obese individuals often have low fitness levels, limiting their ability to complete a typical 30-min bout of continuous exercise. An alternative regimen in obese subjects may be shorter bouts of exercise interspersed throughout the day. OBJECTIVE: The objective of the study was to examine whether intermittent and continuous exercise interventions evoke similar patterns of 24-h GH secretion and whether responses are attenuated in obese subjects or affected by gender. DESIGN: This was a repeated-measures design in which each subject served as their own control. SETTING: This study was conducted at the University of Virginia General Clinical Research Center. SUBJECTS: Subjects were healthy nonobese (n = 15) and obese (n = 14) young adults. INTERVENTIONS: Subjects were studied over 24 h at the General Clinical Research Center on three occasions: control, one 30-min bout of exercise, and three 10-min bouts of exercise. MAIN OUTCOME MEASURES: Twenty-four hour GH secretion was measured. RESULTS: Compared with unstimulated 24-h GH secretion, both intermittent and continuous exercise, at constant exercise intensity, resulted in severalfold elevation of 24-h integrated serum GH concentrations in young adults. Basal and pulsatile modes of GH secretion were attenuated both at rest and during exercise in obese subjects. CONCLUSIONS: The present data suggest that continuous and intermittent exercise training should be comparably effective in increasing 24-h GH secretion.

Estrogen supplementation selectively enhances hypothalamo-pituitary sensitivity to ghrelin in postmenopausal women.

CONTEXT: Sex-steroid hormones amplify pulsatile GH secretion by unknown mechanisms. Ghrelin is the most potent natural GH secretagogue discovered to date. A plausible unifying postulate is that estradiol (E(2)) enhances hypothalamo-pituitary sensitivity to ghrelin (a physiological effect). The hypothesis is relevant to understanding the basis of hyposomatotropism in aging and other relatively hypogonadal states. OBJECTIVE: Our objective was to test the hypothesis that E(2) supplementation potentiates ghrelin's stimulation of pulsatile GH secretion. SETTING: The study was conducted at an academic medical center. SUBJECTS: Healthy postmenopausal women (n = 20) were included in the study. INTERVENTIONS: Separate-day iv infusions of saline vs. five graded doses of ghrelin were performed in volunteers prospectively randomly assigned to receive (n = 8) or not receive (n = 12) transdermal E(2) for 21 d were performed. MEASURES: GH secretion was estimated by deconvolution analysis and abdominal visceral fat mass determined by computerized axial tomography were calculated. RESULTS: E(2) supplementation augmented ghrelin's stimulation of basal (nonpulsatile) GH secretion by 3.6-fold (P = 0.022), increased GH responses to low-dose ghrelin by 2.9-fold (P = 0.035), did not alter ghrelin efficacy, and elicited more regular patterns of acylated ghrelin concentrations during saline infusion (P = 0.033). Abdominal visceral fat negatively determined responses to ghrelin (R = -0.346; P < 0.005). CONCLUSIONS: Transdermal E(2) supplementation potentiates GH secretion stimulated by physiological but not pharmacological concentrations of acylated ghrelin, and concomitantly regularizes patterns of bioactive ghrelin secretion in postmenopausal women. Accordingly, the estrogen milieu appears to control sensitivity of the hypothalamopituitary unit to acylated ghrelin.

Short-term treatment with bromocriptine improves impaired circadian growth hormone secretion in obese premenopausal women.

CONTEXT: A profound reduction of spontaneous as well as stimulated GH secretion has been consistently observed in obesity. Dopamine promotes GH release through activation of dopamine D2 receptors (D2Rs). Dopamine D2R availability in the brain is reduced in obese humans in proportion to body adiposity. We hypothesized that impaired dopamine D2R signaling is mechanistically involved in the deficient GH secretion associated with obesity. OBJECTIVE: To test this hypothesis, we studied the effect of short-term bromocriptine (B) (a D2R agonist) treatment on spontaneous 24-h GH secretion in obese women, while body weight and caloric intake remained constant. DESIGN: This was a prospective, fixed order, cross-over study. SETTING: The study was performed in the Clinical Research Center at Leiden University Medical Center. PARTICIPANTS: There were 18 healthy obese women (body mass index 33.2 +/- 0.6 kg/m2) studied twice in the early follicular phase of their menstrual cycle. INTERVENTION(S): Eight days of treatment with B and placebo (Pl) was performed. MAIN OUTCOME MEASURE(S): Blood was collected during 24 h at 10-min intervals for determination of GH concentrations. GH secretion parameters were calculated using deconvolution analysis. RESULTS: Short-term treatment with B significantly enhanced diurnal GH secretion (Pl 121.4 +/- 16.4 vs. B 155.4 +/- 15.2 microg/liter(volume of distribution).24 h; P = 0.01), whereas IGF-I concentrations remained constant (Pl 22.4 +/- 2.4 vs. B 21.8 +/- 1.6 nmol/liter; P = 0.928). CONCLUSIONS: Activation of dopamine D2Rs by B favorably affects impaired nyctohemeral GH secretion in obese women. Reduced dopaminergic neuronal signaling might be involved in the pathogenesis of obesity associated hyposomatotropism.

Increased basal and pulsatile secretion of FSH and LH in young men with 47,XXY or 46,XX karyotypes.

OBJECTIVE: The regulation of normal sexual maturation and reproductive function is dependent on a precise hormonal regulation at hypothalamic, pituitary, and gonadal levels. The aim of this study was to investigate the neuroendocrine integrity of the pituitary-gonadal axis in patients with primary testicular failure due to supernumerary X chromosomes. DESIGN: Cross-sectional study. METHODS: In this study, 7 untreated patients with primary gonadal insufficiency due to SRY-positive 46,XX (n=4) and 46,XXY karyotypes (n=3) aged 18.8 years and 25 age-matched healthy controls participated. Reproductive hormones, testicular size, and overnight LH and FSH serum profiles and overnight urine LH and FSH excretion were determined. RESULTS: Basal LH and FSH secretion was elevated 6.3- and 25.4-fold respectively in the patients and the amount of LH and FSH secreted per burst were 2.0- and 6.6-fold elevated. We found significantly more LH but not FSH peaks per 24 h, as estimated by the Weibull lambda analysis. There was no difference between approximate entropy ratios or Weibull gamma analyses indicating comparable orderliness and regularity of LH and FSH secretion. Overnight urinary LH and FSH excretion was significantly elevated in patients compared with controls and correlated significantly with calculated total overnight LH and FSH secretion respectively, thus validating deconvolution. CONCLUSION: In this group of patients with severe hypergonadotropic hypogonadism due to a supernumerary X chromosome, higher basal, pulsatile, and total LH and FSH secretion were associated with significantly more LH peaks per 24 h in comparison with healthy controls. Thus, our data indicate that in patients with Klinefelter syndrome and XX male karyotypes the entire hypothalamic-pituitary-gonadal axis has undergone functional changes.

The tailored implementation of the nursing programme 'Coping with Itch'.

AIM: The aim of the study was to implement the nursing programme 'Coping with itch'. BACKGROUND: The nursing programme 'Coping with itch' is intended to reduce itch and to help patients to cope with itch. The programme is carried out at a nurse clinic at the dermatology outpatient department. Implementation of this programme was undertaken in five hospitals in the Netherlands using the tailored implementation approach based on the contingency model of van Linge. METHOD: The implementation procedure started with a diagnostic interview to gather data on the characteristics of the dermatology outpatient departments subsumed in four dimensions: structure, human resource practices, culture and politics. These characteristics were then compared with the demands of the programme. Discrepancies between the demands of the new programme and the characteristics of each organization guided the choice of the implementation strategies. Implementation strategies were mostly directed at the structure or human resource dimensions. Then, the results of the implementation were examined according to three criteria: professional adherence, continuation and barriers, using nurses' self-report forms on the consultations and the Barriers and Facilitators questionnaire. RESULTS: Seventy-seven self-report forms were completed by the nurses for first consultations at the itch clinic and 81 for follow-up consultations. Results concerning professional adherence show that nurses are able to carry out the programme 'Coping with itch'. All five hospitals continued the itch clinic after completion of the implementation study. Two barriers to the implementation were frequently mentioned by the nurses: the necessary time investment and the lack of extra financial compensation. CONCLUSION: The use of a tailored implementation approach has led to the reasonably successful implementation of the nursing programme 'Coping with itch'. Relevance to clinical practice. The contingency model is a useful model for the tailored implementation of a nursing programme in daily practice.