[Failure of a study in forensic psychiatric hospitals : Clinical trial to investigate the additive effect of triptorelin on the efficacy of psychotherapy]. / Vom Scheitern einer Studie in Maßregelvollzugskrankenhäusern : Klinische Prüfung zum additiven Effekt von Triptorelin auf die Wirksamkeit von Psychotherapie.

BACKGROUND: A testosterone-lowering medication is relatively commonly used as a form of treatment for sexual offenders with severe paraphilic disorders in German forensic psychiatric hospitals; however, a double-blind, controlled and randomized study, which investigates the efficacy of this medication, is still lacking. AIM: This article describes the process from the planning to the rejection of a clinical trial over the period from 2009 to 2015. METHODS AND RESULTS: Despite the careful planning with an interdisciplinary team and giving special consideration to the complex legal situation, the Federal Institute for Drugs and Medical Devices (BfArM) rejected the proposed trial in a brief formal letter with reference to the German Drug Law (§ 40 para. 1 p. 3 nr. 4 AMG). The ethics committee of the Hamburg Medical Association considered that clinical research is basically not possible with patients detained in a forensic psychiatric hospital. DISCUSSION: In the opinion of the authors, the described facts illustrate how legal regulations that should protect vulnerable groups in medical research, in a specific case can lead to the fact that a therapy form relevant to the corresponding patient group cannot be scientifically investigated.

FADD is upregulated in relapsing remitting multiple sclerosis.

OBJECTIVE: To elucidate the role of tumor necrosis factor (TNF) receptor signal transduction in multiple sclerosis (MS). METHODS: We performed a cross-sectional analysis of the gene expression of TNF receptor-associated death domain protein (TRADD) and Fas-associated death domain protein (FADD) in peripheral blood leukocytes of 23 relapsing remitting (RR), 19 secondary progressive (SP) and 12 primary progressive (PP) MS patients, as well as of 29 healthy controls by quantitative RT-PCR. Additionally, we monitored a subgroup of 15 RR MS patients longitudinally every 3 months over the time period of 9 months. RESULTS: FADD expression was significantly elevated in RR MS patients compared to the other disease courses (p < 0.048). The median of FADD expression was elevated in the RR MS patient groups compared to the healthy group, but this was not significant (p < 0.053). The median of TRADD expression was elevated in the patient groups compared to the healthy group, but this was not significant (p < 0.14). Neither variable changed significantly over the time course of 9 months. CONCLUSION: FADD elevation in leukocytes might be interpreted as the molecular equivalent of an elevated general inflammatory activity in RR MS patients compared to other disease courses. FADD elevation in RR MS reinforces the concept that different pathophysiological and immunological processes sustain RR MS and SP or PP MS.

Estimation of legal age using calcification stages of third molars in living individuals.

The increased number of adolescents and young adults with unknown or inaccurately given date of birth is a current issue in justice and legal medicine. The objective of this study was to determine the extent to which third molar calcification stages assessed on panoramic X-rays could be useful as additional criteria for forensic age estimation in living individuals, focusing on the legally important ages 17 and 18. In a retrospective multi-center study, the developmental stage of each individual's third molar was analyzed using Demirjian's scale in 2360 cases. Additionally, sex, age and ancestry were assessed. Individuals with the lowest calcification stage of all present molars in stage H were ≥18 years with a likelihood of ≥99.05% in the female (n=388), and ≥99.24% in the male (n=482) population. The lowest calcification stage of all present third molars proved to be useful as an additional reliable criterion for the determination of an age ≥18 years.

TRAF2 is upregulated in relapsing-remitting multiple sclerosis.

OBJECTIVE: To elucidate the role of tumor necrosis factor (TNF) receptor signal transduction in multiple sclerosis (MS). METHODS: We performed a cross-sectional analysis of the gene expression of TRAF2 (TNF receptor-associated factor 2) and RIP (receptor-interacting protein) in peripheral blood leukocytes of 23 relapsing-remitting (RR), 19 secondary progressive (SP) and 12 primary progressive (PP) MS patients as well as of 29 healthy controls by quantitative RT-PCR. Additionally, we monitored a subgroup of 15 RRMS patients longitudinally every 3 months over a 9-month time period. RESULTS: TRAF2 expression was significantly elevated in RRMS patients compared to the other disease courses (p<0.005, respectively) and the control group (p<0.009). RIP expression was significantly elevated in the patient groups compared to the healthy group (phealthy-RR<0.002; phealthy-PP<0.003; phealthy-SP<0.06). Neither variable changed over the 9-month time course. CONCLUSION: TRAF2 and RIP1 elevation in leukocytes might be interpreted as the molecular equivalent of an elevated general inflammatory activity in MS patients compared to healthy control persons. TRAF2 elevation in RRMS reinforces the concept that different pathophysiological and immunological processes sustain RRMS and SPMS or PPMS.

Hemodynamic actions of corticotropin-releasing hormone and proopiomelanocortin derivatives in septic patients.

Proopiomelanocortin (POMC) derivatives and mRNA of POMC have been detected in cardiomyocytes and vascular smooth muscle cells. Increased plasma levels of POMC derivatives have been found in septic patients during cardiovascular deregulation; therefore, we evaluated whether corticotroph-type (ACTH, ß-endorphin, ß-lipotropin) or melanotroph-type (α-melanocyte-stimulating hormone and N-acetyl-ß-END) POMC derivatives have influences on patients' hemodynamics during sepsis. Seventeen septic patients were monitored by pulmonary artery catheter and corticotropin-releasing hormone (CRH) tests were performed by intravenous administration of 100 µg CRH. Before, 15, 30, 45, and 60 minutes after CRH administration, hemodynamic variables were measured, and plasma concentrations of POMC derivatives were determined. After CRH administration, heart rate, cardiac index, and stroke index increased, and the systemic vascular resistance index decreased; moreover, a correlation between ACTH concentration and stroke index as well as an inverse correlation between (α-melanocyte-stimulating hormone concentration and systemic vascular resistance index was observed. CRH and ACTH may have opposite effects on the blood pressure (mean arterial pressure). Immediately after CRH injection mean arterial pressure decreased. ACTH (in contrast to ß-endorphin or ß-lipotropin), released into the cardiovascular compartment 15 minutes after CRH injection, might have raised mean arterial pressure as compatible with the correlation between ACTH levels and stroke index. (α-melanocyte-stimulating hormone appears to have a vasodilative effect during sepsis.

Impact of maintenance immunosuppressive regimens--balance between graft protective suppression of immune functions and a near physiological immune response.

The Symphony study showed superior 1-year kidney graft outcome in patients on immunosuppression with tacrolimus/mycophenolate mofetil (Tacr/MMF). To analyze whether differences in clinical outcome between maintenance regimens may be explained by their impact on clinically relevant immune parameters, we assessed CD4 helper activity, immunoglobulin-secreting cell (ISC) formation, neopterin, sCD30, and intracellular cytokine production in a prospective study in 77 renal transplant recipients treated with cyclosporine A/azathioprine (CsA/Aza), CsA/MMF, Tacr/Aza or Tacr/MMF at 2 years post-transplant. Tacr- compared with CsA-based immunosuppression was independently associated with increased IL-2 (P<0.0001, CD4 cells; P=0.014, CD8 cells) and CD4 cell IL-4 responses (P=0.046; stepwise logistic regression) resulting in physiological responses in Tacr/Aza patients as compared with 25 healthy controls. MMF versus Aza treatment was proven to be an independent variable associated with suppression of CD4 cell IL-10 responses (P=0.008), B-cell IL-6R expression (P<0.0001) and ISC formation [P=0.020, staphylococcus cowan strain I (SAC I); P=0.021, pokeweed mitogen (PWM)]. Our data suggest that Tacr/MMF had the most effective impact on graft protective Th2 responses (enhanced CD4 cell IL-4 by Tacr, decreased CD4 cell IL-10 responses by MMF) and suppression of B-cell functions (MMF), whereas Tacr/Aza was associated with physiological IL-2 and IL-4 and stronger humoral responses which may reduce the risk of infectious disease complications.

Impact of Parallel Topical Treatment with Nadifloxacin and Adapalene on Acne Vulgaris Severity and Quality of Life: A Prospective, Uncontrolled, Multicentric, Noninterventional Study.

INTRODUCTION: Daily parallel application of adapalene and nadifloxacin has been determined to be effective and well tolerated in patients with acne vulgaris in randomized, controlled clinical studies. Here, the authors report the results from a large, prospective, uncontrolled, multicentric, noninterventional study under real-life conditions in Germany. The effect of treatment on acne severity, safety, and, for the first time, health-related quality of life (HRQoL) was investigated. METHODS: Of the 292 patients (safety collective: 231 adults, 61 adolescents) who had at least grade 4 acne vulgaris on the face as per the Leeds Revised Acne Grading (LRAG), 273 (efficacy collective: 213 adults, 60 adolescents) were treated with adapalene 0.1% cream or gel and nadifloxacin 1% cream for the defined minimum of 28 days. Patients were evaluated for acne severity, acne-related facial symptoms, HRQoL, overall assessment of therapy, and safety. RESULTS: After the median treatment duration of 37 and 38 days (adults and adolescents, respectively), 93.4% and 85.0% of adults and adolescents, respectively, exhibited a sustained decrease in acne severity. The LRAG decreased by at least 3 scores in 29.1% and 24.6% of female and male adults, respectively. HRQoL improved in 67.9% and 63.5% of adults and adolescents, respectively (median improvement in the Dermatology Life Quality Index scores per patient of 3.0 [female adults], 1.0 [male adults], and 2.0 for all adolescents in the Children's Dermatology Life Quality Index). Female adults were more impaired in terms of HRQoL compared to male adults. The 2 best overall efficacy ratings were provided by physicians in 79.3% and 69.5% and by patients in 68.5% and 58.3% of adult and adolescent cases, respectively. The treatment was well tolerated, as reflected in the low number of 9 mild adverse events (AEs), all of which resolved without treatment. However, 4 patients terminated the study prematurely due to AEs. CONCLUSION: In this study, the parallel use of adapalene and nadifloxacin for at least 5 weeks resulted in a rapid improvement in acne severity, an increase in HRQoL, and a good safety profile. Therefore, it represents a promising treatment option that offers the possibility of flexible therapy adjustment.

Dose escalation improves therapeutic outcome: post hoc analysis of data from a 12-week, multicentre, double-blind, parallel-group trial of trospium chloride in patients with urinary urge incontinence.

BACKGROUND: Flexible dosing of anticholinergics used for overactive bladder (OAB) treatment is a useful strategy in clinical practice for achieving a maximum effective and maximum tolerated level of therapeutic benefit. In this post hoc analysis we evaluated the efficacy and tolerability of trospium chloride treatment for urinary urge incontinence (UUI) with focus on flexible dosing. METHODS: The data came from a 12-week, randomised, double-blind, phase IIIb study in which 1658 patients with urinary frequency plus urge incontinence received trospium chloride 15 mg TID (n = 828) or 2.5 mg oxybutynin hydrochloride TID (n = 830). After four weeks, daily doses were doubled and not readjusted in 29.2% (242/828) of patients in the trospium group, and in 23.3% (193/830) in the oxybuytnin group, until the end of treatment. We assessed the absolute reduction in weekly UUI episodes and the change in intensity of dry mouth, recorded in patients' micturition diaries. Adverse events were also evaluated. Statistics were descriptive. RESULTS: Dose escalation of either trospium or oxybutynin increased reduction in UUI episodes in the population studied. At study end, there were no relevant differences between the "dose adjustment" subgroups and the respective "no dose adjustment" subgroups (trospium: P = 0.249; oxybutynin: P = 0.349). After dose escalation, worsening of dry mouth was higher in both dose adjusted subgroups compared to the respective "no dose adjustment" subgroups (P < 0.001). Worsening of dry mouth was lower in the trospium groups than in the oxybutynin groups (P < 0.001). Adverse events were increased in the dose adjusted subgroups. CONCLUSIONS: Flexible dosing of trospium was proven to be as effective, but better tolerated as the officially approved adjusted dose of oxybutynin. TRIAL REGISTRATION (PARENT STUDY): The study was registered with the German Federal Institute for Drugs and Medical Devices (BfArM, Berlin, Germany), registration number 4022383, as required at the time point of planning this study.

Safety and efficacy of sertaconazole nitrate cream 2% in the treatment of tinea pedis interdigitalis: a subgroup analysis.

Sertaconazole nitrate is a broad-spectrum antifungal agent indicated in the United States for the treatment of tinea pedis interdigitalis. The objective of this subgroup analysis was to evaluate the safety and efficacy of sertaconazole nitrate cream 2%, specifically in participants with tinea pedis interdigitalis (ie, fungal skin disease of the toe web) of dermatophyte origin. A total of 92 participants were included in this analysis. The primary end points were eradication of the pathogen (confirmed by fungal culture results) and reduction in total clinical score (TCS) of at least 2 points. Secondary end points included reducing signs and symptoms and reporting adverse events (AEs). After 4 weeks of treatment, 88.8% (79/89) of evaluable participants achieved success on the primary end points. Most participants also demonstrated substantial improvement in signs and symptoms after 4 weeks of treatment: 63.7% (58/91) were free of erythema, 33.0% (30/91) were free of desquamation, and 91.2% (83/91) were free of itch. The rate of reported AEs was low (8.7% [8/92]), and none were considered serious. These findings indicate that sertaconazole nitrate cream 2% is highly safe and effective in the treatment of tinea pedis interdigitalis.

Comparative study of 2% sertaconazole solution and cream formulations in patients with tinea corporis, tinea pedis interdigitalis, or a corresponding candidosis.

BACKGROUND: Based on the results of numerous preclinical and clinical studies, sertaconazole can be considered a safe and effective drug for the treatment of fungal skin infections. OBJECTIVE: The objective of the study was to compare the efficacy of a solution containing 2% sertaconazole with the well established 2% sertaconazole cream formulation in patients with tinea corporis, tinea pedis interdigitalis, or a corresponding candidosis. METHODS: This was a prospective, open-label, randomized, controlled, parallel-group, multicenter, noninferiority therapy study. Patients received either sertaconazole solution or cream twice daily for 28 days. The full analysis set comprised 160 patients in the solution group and 153 patients in the cream group. The primary efficacy parameter was a combination of culture test result and total clinical score. Efficacy was defined by eradication of the pathogen and reduction of the total clinical score between pretreatment and the final visit. RESULTS: Efficacy was documented in 90.6% of patients using the solution and 88.9% of those using the cream (full analysis set). No adverse events occurred. CONCLUSION: Solution and cream formulations of 2% sertaconazole applied for 28 days were associated with comparable efficacy and safety in the treatment of fungal skin infections.

Preoperative concentration of beta-lipotropin immunoreactive material in cerebrospinal fluid: a predictor of postoperative pain?

Levels of beta-endorphin immunoreactive material (IRM) in cerebrospinal fluid (CSF) have been reported to correlate inversely with postoperative morphine requirement. Considering proopiomelanocortin (POMC) derivatives as predictors for sensitivity to postoperative pain, we determined authentic beta-endorphin (beta-endorphin(1-31)), beta-lipotropin IRM, N-acetyl-beta-endorphin IRM and ACTH in CSF of 17 patients undergoing hip or knee arthroplasty, before surgery (t(A)), immediately after termination of propofol infusion and still under spinal anesthesia (t(B)), under postoperative pain (t(C)) and one day after surgery (t(D)); patients rated their severity of pain on a visual analogue scale (VAS) at those four times. In all patients CSF concentrations of N-acetyl-beta-endorphin IRM and beta-lipotropin IRM were found to be increased after terminating the propofol infusion with spinal anesthesia still effective at t(B). Patients did not feel pain at times t(A), t(B) or t(D); however, they reported moderate to considerable pain at t(C). There were no correlations of postoperative pain severity at t(C) with ACTH, beta-endorphin(1-31) or N-acetyl-beta-endorphin IRM concentrations in CSF. In contrast, we observed significant inverse correlations (Spearman's rank correlation coefficients between -0.83 and -0.85, p<0.01) for postoperative pain severity with beta-lipotropin IRM concentrations in CSF at t(C), and, in addition, at t(A), t(B) and t(D); thus, postoperative pain severity appeared to be dependent on a central system controlling sensitivity to pain, linked to a POMC system releasing beta-lipotropin IRM into CSF and already active at times t(A) and t(B). We conclude that beta-lipotropin IRM in CSF might be considered to serve as a predictor of sensitivity to postoperative pain.

Persistent high activity of the fetal adrenal cortex in preterm infants: is there a clinical significance?

BACKGROUND: In preterm infants, the activity of the fetal adrenal cortex continues until term. Dehydroepiandrosterone sulphate can block the synthesis of surfactant in vitro. The incidence of pulmonary disease is higher in male than in female preterm infants. OBJECTIVE: To investigate the relationship between urinary excretion of fetal zone steroids (3beta-OH-5-ene-steroids) and the severity of lung disease in preterm infants with respect to gender. PATIENTS AND METHODS: 3beta-OH-5-ene-steroids were profiled by gas chromatography-mass spectrometry in 24-h urinary samples in 61 preterm infants of less than 30 weeks gestational age. RESULTS: The incidence of respiratory distress syndrome treated with surfactant in females (n = 30) was 47% and in males (n = 31) 71%, p = 0.07. Medians of total excretion rates of fetal zone steroids (microg/kg/d) in female (male) preterm infants were at day 1: 1,317 (895); day 2: 3,154 (7,723), p = 0.03; day 3: 5,502 (9,494), p = 0.08; day 5: 7,140 (10,407); week 2: 8,731 (9,720); week 3: 8,571 (10,079); week 4: 7,620 (7,825). Regression analysis did not reveal a significant influence of maximum excretion rates of fetal zone steroids or gender on the incidence of respiratory distress syndrome treated with surfactant. CONCLUSIONS: Excretion rates of fetal zone steroids were 4-fold higher than previously reported indicating a persistent high activity of the fetal adrenal zone in preterm infants. Excretion rates of fetal zone steroids were significantly higher in male preterm infants compared to females at day 2 (trend at day 3) but did not have a significant influence on the incidence of respiratory distress syndrome.

Cortisol production rates in preterm infants in relation to growth and illness: a noninvasive prospective study using gas chromatography-mass spectrometry.

CONTEXT: Whereas intrauterine growth and maturation depend on low cortisol levels, an adrenal stress response postnatally is thought to be mandatory in preterm infants. OBJECTIVE: The goal of this study was to determine cortisol production rates (CPRs) in preterm infants during early life with extreme illness and, thereafter, during extrauterine growth and maturation. DESIGN: We describe a longitudinal observational study. SETTING: The study was conducted at a university neonatal intensive care unit. PATIENTS AND METHODS: Seventeen well (27.9 +/- 1.8 wk) and 44 ill (27.3 +/- 1.6 wk) preterm infants were classified by the Score for Neonatal Acute Physiology. Glucocorticoid metabolites were profiled by gas chromatography-mass spectrometry in 24-h urinary samples. Urine was collected noninvasively using cellulose nappies and extracted by hydraulic press. RESULTS: Medians of CPRs (microg kg(-1) d(-1) mg creatinine) in ill (well) preterm infants were as follows: at d 1, 35 (40); d 2, 35 (40); d 3, 48 (53); d 5, 47 (41); wk 2, 72 (48); wk 3, 73 (37); wk 4, 54 (26). Regression analysis revealed a significant inverse influence of gestational age (P < 0.005) on the maximum of CPRs but not of severity of illness (Score for Neonatal Acute Physiology; P = 0.72). A mature adrenal response was found in only 12 of 44 (27%) ill preterm infants, who had CPRs higher than the 3-fold median of CPRs of well infants. This mature adrenal response was associated with a significantly higher incidence of cerebral bleeding: 9 of 12 (75%) vs. 8 of 32 (25%) without such a response (P = 0.003). During growth, CPRs of ill (well) preterm infants decreased: at month 2, 30 (18); month 3, 18 (22); correlation between weight gain and decrease of CPRs in ill infants between wk 4 and month 3, r = -0.48 (P = 0.027). CONCLUSIONS: Severity of illness did not have a significant influence on CPRs in preterm infants. However, the highest CPRs were associated with a significantly higher incidence of cerebral bleeding. During growth, CPRs decreased significantly, suggesting that preterm infants have the ability to regulate cortisol production. CPRs in ill preterm infants might reflect inadequate stress reaction, but this could also reveal persistence of fetal protective mechanisms against high catabolic cortisol concentrations.

Sperm function and assisted reproduction technology.

The evaluation of different functional sperm parameters has become a tool in andrological diagnosis. These assays determine the sperm's capability to fertilize an oocyte. It also appears that sperm functions and semen parameters are interrelated and interdependent. Therefore, the question arose whether a given laboratory test or a battery of tests can predict the outcome in in vitro fertilization (IVF). One-hundred and sixty-one patients who underwent an IVF treatment were selected from a database of 4178 patients who had been examined for male infertility 3 months before or after IVF. Sperm concentration, motility, acrosin activity, acrosome reaction, sperm morphology, maternal age, number of transferred embryos, embryo score, fertilization rate and pregnancy rate were determined. In addition, logistic regression models to describe fertilization rate and pregnancy were developed. All the parameters in the models were dichotomized and intra- and interindividual variability of the parameters were assessed. Although the sperm parameters showed good correlations with IVF when correlated separately, the only essential parameter in the multivariate model was morphology. The enormous intra- and interindividual variability of the values was striking. In conclusion, our data indicate that the andrological status at the end of the respective treatment does not necessarily represent the status at the time of IVF. Despite a relatively low correlation coefficient in the logistic regression model, it appears that among the parameters tested, the most reliable parameter to predict fertilization is normal sperm morphology. (Reprod Med Biol 2005; 4: 7-30).

Rupatadine in Established Treatment Schemes Improves Chronic Spontaneous Urticaria Symptoms and Patients' Quality of Life: a Prospective, Non-interventional Trial.

INTRODUCTION: Chronic spontaneous urticaria (CSU) is a common and hard to treat condition associated with a substantial negative impact on patients' quality of life (QoL). Clinical studies have shown that rupatadine is effective and safe in the treatment of CSU, but data from routine clinical care are scarce. Therefore, we assessed the effectiveness and tolerability of rupatadine in established dosages on CSU activity and patients' QoL in a routine daily practice setting. METHODS: This was an open, prospective, non-interventional study performed in 146 dermatological practices in Germany. CSU patients for whom treatment with rupatadine was indicated were eligible to participate. Key symptoms of urticaria activity and their impact on patients' QoL were assessed at the beginning and the end of treatment. Adverse events (AEs) and withdrawals, as well as the dosage regimens chosen, were documented. Patients and physicians were requested to rate effectiveness and tolerability of therapy at the final visit. All statistical analyses were descriptive. RESULTS: The majority of the 660 patients screened to be treated (median age 44 years, IQR = 31-59 years, n = 654) received rupatadine 10 mg tablets once (477 patients) or twice (105 patients) daily for a median time of 28 days. After treatment, 93.2% of the patients (606/650) reported a clear overall improvement of symptoms. Rupatadine significantly reduced the urticaria activity score (UAS7) as well as the frequency and severity of existing angioedema episodes. Similarly all domains of the urticaria-specific QoL questionnaire (CU-Q2oL) were markedly improved. The majority of physicians and patients rated rupatadine treatment as effective and well tolerated. There were 39 (5.9%) early treatment withdrawals, and 21 patients (3.2%) experienced AEs. CONCLUSION: Rupatadine when given according to the routine treating schemes improves symptoms and CU-Q2oL of CSU patients; the drug is also safe and well tolerated. FUNDING: Dr. R. Pfleger GmbH.

Treatment of locoregional metastases of malignant melanomas with radiotherapy and intralesional beta-interferon injection.

Intralesional injection of beta-interferon can lead to remission of metastatic melanomas. Simultaneous radiotherapy may augment the effect of these injections. The effect of intralesional beta-interferon injections combined with radiotherapy was examined in patients with metastatic malignant melanoma. A total of 20 patients with inoperable, incapacitating and disfiguring malignant melanoma metastases were treated with simultaneous external beam radiotherapy (electrons and/or photons) and intralesional injection of beta-interferon. The total radiation dosage ranged from 40-50 Gy, fractionated as 1.8 Gy five times per week. beta-Interferon (Fiblaferon) 3-5 million units per injection was administered three times weekly until symptoms disappeared or until termination of therapy. One patient was treated with beta-interferon alone; the area harbouring the tumour had been previously irradiated. Five patients treated in this way showed partial remission after combined therapy and 12 showed complete remission, with permanent regression of metastases. The latter group included five patients with lengthy survival times, including one patient who has been free of symptoms for 7 years following treatment. Injected metastases showed complete regression in the patient who was treated exclusively with beta-interferon post-irradiation. In conclusion, combined treatment with radiotherapy and intratumoral injection of beta-interferon controlled local tumour growth in inoperable metastatic malignant melanomas.

Major cardiac surgery induces an increase in sex steroids in prepubertal children.

While the neuroprotective benefits of estrogen and progesterone in critical illness are well established, the data regarding the effects of androgens are conflicting. Surgical repair of congenital heart disease is associated with significant morbidity and mortality, but there are scant data regarding the postoperative metabolism of sex steroids in this setting. The objective of this prospective observational study was to compare the postoperative sex steroid patterns in pediatric patients undergoing major cardiac surgery (MCS) versus those undergoing less intensive non-cardiac surgery. Urinary excretion rates of estrogen, progesterone, and androgen metabolites (µg/mmol creatinine/m(2) body surface area) were determined in 24-h urine samples before and after surgery using gas chromatography-mass spectrometry in 29 children undergoing scheduled MCS and in 17 control children undergoing conventional non-cardiac surgery. Eight of the MCS patients had Down's syndrome. There were no significant differences in age, weight, or sex between the groups. Seven patients from the MCS group showed multi-organ dysfunction after surgery. Before surgery, the median concentrations of 17ß-estradiol, pregnanediol, 5α-dihydrotestosterone (DHT), and dehydroepiandrosterone (DHEA) were (control/MCS) 0.1/0.1 (NS), 12.4/11.3 (NS), 4.7/4.4 (NS), and 2.9/1.1 (p=0.02). Postoperatively, the median delta 17ß-estradiol, delta pregnanediol, delta DHT, and delta DHEA were (control/MCS) 0.2/6.4 (p=0.0002), -3.2/23.4 (p=0.013), -0.6/3.7 (p=0.0004), and 0.5/4.2 (p=0.004). Postoperative changes did not differ according to sex. We conclude that MCS, but not less intensive non-cardiac surgery, induced a distinct postoperative increase in sex steroid levels. These findings suggest that sex steroids have a role in postoperative metabolism following MCS in prepubertal children.

Effects of corticotropin-releasing hormone on proopiomelanocortin derivatives and monocytic HLA-DR expression in patients with septic shock.

Little is known about interactions between immune and neuro-endocrine systems in patients with septic shock. We therefore evaluated whether the corticotropin-releasing hormone (CRH) and/or proopiomelanocortin (POMC) derivatives [ACTH, ß-endorphin (ß-END), ß-lipotropin (ß-LPH), α-melanocyte stimulating hormone (α-MSH) or N-acetyl-ß-END (Nac-ß-END)] have any influences on monocyte deactivation as a major factor of immunosuppression under septic shock conditions. Sixteen patients with septic shock were enrolled in a double-blind, cross-over and placebo controlled clinical study; 0.5µg/(kgbodyweighth) CRH (or placebo) were intravenously administered for 24h. Using flow cytometry we investigated the immunosuppression in patients as far as related to the loss of leukocyte surface antigen-DR expression on circulating monocytes (mHLA-DR). ACTH, ß-END immunoreacive material (IRM), ß-LPH IRM, α-MSH and Nac-ß-END IRM as well as TNF-α and mHLA-DR expression were determined before, during and after treatment with CRH (or placebo). A significant correlation between plasma concentration of α-MSH and mHLA-DR expression and an inverse correlation between mHLA-DR expression and TNF-α plasma level were found. Additionally, a significant increase of mHLA-DR expression was observed 16h after starting the CRH infusion; 8h later, the mHLA-DR expression had decreased again. Our results indicate that the up-regulation of mHLA-DR expression after CRH infusion is not dependent on the release of POMC derivatives. From the correlation between plasma concentration of α-MSH and mHLA-DR expression, we conclude that in patients with septic shock the down-regulation of mHAL-DR expression is accompanied by the loss of monocytic release of α-MSH into the cardiovascular compartment.

Coronary stenting before coronary artery bypass graft surgery in diabetic patients does not increase the perioperative risk of surgery.

OBJECTIVE: A negative relationship between coronary stenting before coronary artery bypass graft (CABG) surgery and the perioperative mortality and morbidity has been shown in diabetic patients. We tried to assess this relationship in a 2-institution database. METHODS: In the years 2005 and 2006, 1125 of 3311 patients undergoing CABG surgery had diabetes mellitus (33.9%), and 185 (16.4%) of the diabetic patients had at least 1 previous stent. There was no evidence of any clinically significant difference in the preoperative and intraoperative parameters between diabetics with or without previous stents. RESULTS: Thirty-day mortality (no-stent group, 3.86%; stent group, 1.62%) and postoperative major adverse cardiovascular and cerebrovascular events (MACCEs; mortality, stroke, myocardial infarction, renal failure) (no-stent group, 12.2%; stent group, 5.9%) occurred more often in diabetic patients without coronary stents. Logistic regression for 30-day mortality using possible confounders including preoperative stent showed a significant positive effect of preoperative coronary stenting (OR, 0.157; 95% CI limits, 0.033-0.737). Taking percutaneous coronary intervention out of the calculation model, this positive effect was no longer significant (OR, 0.344; CI, 0.091-1.298). Logistic regression for perioperative MACCE, with as well as without percutaneous coronary intervention as a confounder, also showed a significant positive effect of preoperative coronary stenting (OR, 0.231; 95% CI, 0.091-0.590). CONCLUSIONS: Coronary stenting before CAGB in diabetic patients does not predispose to a higher perioperative risk regarding mortality and morbidity after CABG surgery.

Maturation of adrenal function determined by urinary glucocorticoid steroid excretion rates in preterm infants of more than 30 weeks of gestational age.

BACKGROUND: Data on the adrenal stress response of preterm infants between 30 and 36 weeks are inconsistent. OBJECTIVE: To test the hypothesis that there is a positive association between illness severity and cortisol production rates (CPR) in preterm infants >30 weeks. PATIENTS AND METHODS: In a prospective longitudinal observational study, glucocorticoid metabolites were profiled by gas chromatography-mass spectrometry in 24-hour urinary samples. Excretion rates of glucocorticoid metabolites were summed to calculate CPR in 61 well (mean +/- SD: 33.6 +/- 1.7 weeks) and 20 ill (33.2 +/- 1.6 weeks) preterm infants. Illness severity was measured by the score for neonatal acute physiology (SNAP). RESULTS: During the first week of life, SNAP were higher in the group of ill compared to well infants. Medians of CPR (microg/kg/d per mg creatinine) in ill (well) infants were: 1st day, 31 (28); 2nd day, 24 (28); 3rd day, 27 (26); 5th day, 28 (17); 2nd week, 20 (19); 3rd week, 17 (19); 4th week, 16 (16); and 2nd month, 17 (23). There was a significant association between the maximum of SNAP and the maximum of CPR (OR 3.7; 95% CI: 1.2-11.5; p = 0.02) in a logistic regression model which comprised gestational age, mode of delivery, gender and the administration of prenatal steroids as covariables. CONCLUSION: There was a positive association between severity of illness and CPR in preterm infants >30 weeks, indicating a maturation of the adrenal stress response.