Pre-transplant testosterone and outcome of men after allogeneic stem cell transplantation.

Testosterone is an important determinant of endothelial function and vascular health in men. As both factors play a role in mortality after allogeneic stem cell transplantation (alloSCT), we retrospectively evaluated the impact of pre-transplant testosterone levels on outcome in male patients undergoing alloSCT. In the discovery cohort (n=346), an impact on outcome was observed only in the subgroup of patients allografted for acute myeloid leukemia (AML) (n=176, hereafter termed 'training cohort'). In the training cohort, lower pre-transplant testosterone levels were significantly associated with shorter overall survival (OS) [hazard ratio (HR) for a decrease of 100 ng/dL: 1.11, P=0.045]. This was based on a higher hazard of non-relapse mortality (NRM) (cause-specific HR: 1.25, P=0.013), but not relapse (cause-specific HR: 1.06, P=0.277) in the multivariable models. These findings were replicated in a confirmation cohort of 168 male patients allografted for AML in a different center (OS, HR: 1.15, P=0.012 and NRM, cause-specific HR: 1.23; P=0.008). Next, an optimized cut-off point for pre-transplant testosterone was derived from the training set and evaluated in the confirmation cohort. In multivariable models, low pre-transplant testosterone status (<250 ng/dL) was associated with worse OS (hazard ratio 1.95, P=0.021) and increased NRM (cause-specific HR 2.68, P=0.011) but not with relapse (cause-specific HR: 1.28, P=0.551). Our findings may provide a rationale for prospective studies on testosterone/androgen assessment and supplementation in male patients undergoing alloSCT for AML.

[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.

Kyphoplasty in patients with multiple myeloma a retrospective comparative pilot study.

BACKGROUND: This retrospective study of 73 myeloma patients with painful vertebral lesions compares clinical and radiomorphological outcomes up to 2 years after additional kyphoplasty, radiation therapy or systemic treatment only. METHODS: We assessed pain, disability and radiomorphological parameters by visual analogue scale (VAS 0-100), Oswestry Disability Index and by re-evaluating available follow-up X-rays, respectively, in patients that were treated according to a clinical pathway. RESULTS: After 2 years the VAS score was reduced in all groups by 66 ± 8.2 (kyphoplasty), 35 ± 10.5 (radiation therapy) and 38 ± 20.5 (systemic therapy only). Only after kyphoplasty we observed a significantly reduced Oswestry Disability Index after 1 year (P < 0.001). Vertebral height remained stable after kyphoplasty (P = 0.283), in contrast to a progressive height loss in the other groups (P = 0.013 and P = 0.015 for radiation and systemic therapy only, respectively). Two years after kyphoplasty and radiotherapy the overall vertebral fracture incidence was significantly decreased as compared to the group after systemic therapy only (9.7% of all thoracic and lumbar vertebrae had new vertebral fractures after systemic therapy only, 2% after kyphoplasty (P < 0.001), 4.8% after radiation (P = 0.032)). CONCLUSION: Additional kyphoplasty was more effective than additional radiation or systemic therapy in terms of pain relief, reduction of pain associated disability and reduction of fracture incidence of the entire lumbar and thoracic spine.

Osteoplastic procedures for the treatment of vertebral complications in multiple myeloma patients.

Pain induced by vertebral fracture in multiple myeloma can be treated by an osteoplastic procedure. The magnitude of the pain reduction by the procedure depends on the presence of additional causes for pain as spondylosis deformans, osteochondrosis, stenosis of the spinal canal, or intervertebral nerve compression. To identify additional reasons for pain apart from a vertebral fracture-induced pain, a detailed preoperative analysis of the patients complaints is crucial for the outcome after an osteoplastic procedure. In addition, the technical aspects for performing the procedure and potential complications have to be considered as well as the stability of the cortical bone of the respective vertebral body. A complete collapse of the vertebra (vertebra plana) is an unfavorable situation for any osteoplastic procedure. In case of inflammatory or infectious vertebral lesions (e.g. spondylodiscitis) osteoplastic procedures are contraindicated. An interdisciplinary discussion of the individual case among oncologists, radiotherapists, trauma/spien surgeons, radiologists, and osteologists/endocrinologists is a prerequisite for the identification of patients who will truly benefit from an osteoplastic procedure and to avoid overtreatment of the patient and economical exploitation of healthcare providers.

Concerted action of androgens and mechanical strain shifts bone metabolism from high turnover into an osteoanabolic mode.

Adhesion of bone cells to the extracellular matrix is a crucial requirement for osteoblastic development and function. Adhesion receptors connect the extracellular matrix with the cyto-skeleton and convey matrix deformation into the cell. We tested the hypothesis that sex hormones modulate mechanoperception of human osteoblastic cells (HOB) by affecting expression of adhesion molecules like fibronectin and the fibronectin receptor. Only dihydrotestosterone (DHT), but not 17beta-estradiol, stimulated fibronectin (137%) and fibronectin receptor (252%) protein expression. The effects of deformation strain on HOB metabolism were investigated in a FlexerCell strain unit. Cyclically applied strain (2.5% elongation) increased DNA synthesis (125%) and interleukin-6 (IL-6) production (170%) without significantly affecting alkaline phosphatase (AP) activity, type I collagen (PICP), or osteoprotegerin (OPG) secretion. 10 nM DHT pretreatment abolished the mitogenic response of HOB to strain and increased AP activity (119%), PICP (163%), and OPG production (204%). In conclusion, mechanical strain stimulates bone remodeling by increasing HOB mitosis and IL-6 production. DHT enhances the osteoanabolic impact of deformation strain by increasing bone formation via increased AP activity and PICP production. At the same time, bone resorption is inhibited by decreased IL-6 and increased OPG secretion into the bone microenvironment.

Three-year outcomes after kyphoplasty in patients with osteoporosis with painful vertebral fractures.

PURPOSE: Kyphoplasty immediately improves pain and mobility in patients with painful osteoporotic vertebral fractures, but long-term clinical outcomes are still unclear. This controlled trial evaluates pain, mobility and fracture incidence 3 years after kyphoplasty. MATERIALS AND METHODS: Kyphoplasty was performed in 40 patients with painful osteoporotic vertebral fractures; 20 patients who were selected for kyphoplasty but chose not to undergo the procedure served as controls. All patients received pharmacologic antiosteoporosis treatment, pain medication, and physiotherapy. Pain (visual analog scale of 0-100), mobility (European Vertebral Osteoporosis Study questionnaire score of 0-100), and incident vertebral fractures were assessed at baseline, postprocedurally, and after 12 and 36 months. RESULTS: Pain score improved after kyphoplasty from 73.8 to 55.9 (immediately after kyphoplasty), 55.6 (12 months), and 54.0 (36 months; P < .001). Pain score in the control group changed from 66.4 to 65.7 at 12 months and 64.0 at 36 months (P = .521). The pain score of the kyphoplasty group was significantly improved versus controls after 36 months (P = .023). Mobility score improved after kyphoplasty from 43.8 to 54.2 (immediately after kyphoplasty), 54.5 (12 months), and 54.8 (36 months; P = .0008) and remained increased (P = .308) compared with controls (39.8 immediately after kyphoplasty, 44.3 at 12 months, and 43.6 at 36 months). The incidence of new vertebral fractures after kyphoplasty was significantly reduced versus controls after 3 years (P = .0341). CONCLUSIONS: Kyphoplasty reduces pain and improves mobility as long as 3 years after the procedure. The long-term risk of new vertebral fractures after kyphoplasty of chronically painful vertebral fractures is reduced versus controls.

Lower plasma cholesterol, LDL-cholesterol and LDL-lipoprotein subclasses in adult phenylketonuria (PKU) patients compared to healthy controls: results of NMR metabolomics investigation.

BACKGROUND: Phenylketonuria (PKU; OMIM#261600) is a rare metabolic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene resulting in high phenylalanine (Phe) in blood and brain. If not treated early this results in intellectual disability, behavioral and psychiatric problems, microcephaly, motor deficits, eczematous rash, autism, seizures, and developmental problems. There is a controversial discussion of whether patients with PKU have an additional risk for atherosclerosis due to interference of Phe with cholesterol synthesis and LDL-cholesterol regulation. Since cholesterol also plays a role in membrane structure and myelination, better insight into the clinical significance of the impact of Phe on lipoprotein metabolism is desirable. In 22 treated PKU patients (mean age 38.7 years) and 14 healthy controls (mean age 35.2 years), we investigated plasma with NMR spectroscopy and quantified 105 lipoprotein parameters (including lipoprotein subclasses) and 24 low molecular weight parameters. Analysis was performed on a 600 MHz Bruker AVANCE IVDr spectrometer as previously described. RESULTS: Concurrent plasma Phe in PKU patients showed a wide range with a mean of 899 µmol/L (50-1318 µmol/L). Total cholesterol and LDL-cholesterol were significantly lower in PKU patients versus controls: 179.4 versus 200.9 mg/dL (p < 0.02) and 79.5 versus 104.1 mg/dL (p < 0.0038), respectively. PKU patients also had lower levels of 22 LDL subclasses with the greatest differences in LDL2 Apo-B, LDL2 Particle Number, LDL2-phospholipids, and LDL2-cholesterol (p < 0.0001). There was a slight negative correlation of total cholesterol and LDL-cholesterol with concurrent Phe level. VLDL5-free cholesterol, VLDL5-cholesterol, VLDL5-phospholipids, and VLDL4-free cholesterol showed a significant (p < 0.05) negative correlation with concurrent Phe level. There was no difference in HDL and their subclasses between PKU patients and controls. Tyrosine, glutamine, and creatinine were significantly lower in PKU patients compared to controls, while citric and glutamic acids were significantly higher. CONCLUSIONS: Using NMR spectroscopy, a unique lipoprotein profile in PKU patients can be demonstrated which mimics a non-atherogenic profile as seen in patients treated by statins.

Empagliflozin Effectively Lowers Liver Fat Content in Well-Controlled Type 2 Diabetes: A Randomized, Double-Blind, Phase 4, Placebo-Controlled Trial.

OBJECTIVE: To evaluate whether the sodium-glucose cotransporter 2 inhibitor empagliflozin (EMPA) reduces liver fat content (LFC) in recent-onset and metabolically well-controlled type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: Patients with T2D (n = 84) (HbA1c 6.6 ± 0.5% [49 ± 10 mmol/mol], known disease duration 39 ± 27 months) were randomly assigned to 24 weeks of treatment with 25 mg daily EMPA or placebo. The primary end point was the difference of the change in LFC as measured with magnetic resonance methods from 0 (baseline) to 24 weeks between groups. Tissue-specific insulin sensitivity (secondary outcome) was assessed by two-step clamps using an isotope dilution technique. Exploratory analysis comprised circulating surrogate markers of insulin sensitivity and liver function. Statistical comparison was done by ANCOVA adjusted for respective baseline values, age, sex, and BMI. RESULTS: EMPA treatment resulted in a placebo-corrected absolute change of -1.8% (95% CI -3.4, -0.2; P = 0.02) and relative change in LFC of -22% (-36, -7; P = 0.009) from baseline to end of treatment, corresponding to a 2.3-fold greater reduction. Weight loss occurred only with EMPA (placebo-corrected change -2.5 kg [-3.7, -1.4]; P < 0.001), while no placebo-corrected change in tissue-specific insulin sensitivity was observed. EMPA treatment also led to placebo-corrected changes in uric acid (-74 mol/L [-108, -42]; P < 0.001) and high-molecular-weight adiponectin (36% [16, 60]; P < 0.001) levels from 0 to 24 weeks. CONCLUSIONS: EMPA effectively reduces hepatic fat in patients with T2D with excellent glycemic control and short known disease duration. Interestingly, EMPA also decreases circulating uric acid and raises adiponectin levels despite unchanged insulin sensitivity. EMPA could therefore contribute to the early treatment of nonalcoholic fatty liver disease in T2D.

Direct effects of osteoprotegerin on human bone cell metabolism.

PURPOSE: Osteoprotegerin (OPG) affects bone metabolism by intercepting the RANK-RANKL interaction which prevents osteoclastic differentiation and consequently reduces bone resorption. Different bone phenotypes of mice overexpressing OPG and of mice with knockdown of receptor activator of NF-kappaB (RANK) or RANK-ligand (RANKL) suggest that the mechanism of action of the OPG-RANKL-RANK system in regulating bone remodeling is not completely understood. Furthermore, OPG increases bone mass and density independently from reduced osteoclastogenesis which is consistent with the possibility that OPG may directly affect bone metabolism beyond its known role as decoy receptor for RANKL. METHODS: We treated primary human osteoblastic cells with OPG and inhibitory anti-RANKL antibodies and measured cellular ALP activity, in vitro mineralization, vitronectin receptor protein expression and ERK phosphorylation. We also analyzed the mRNA co-expression of ALP and OPG ex vivo in bone biopsies from acute and old stable vertebral fractures. RESULTS: OPG directly increased ALP activity and in vitro mineralization of HOC, enhanced expression of the vitronectin receptor thereby increasing adherence of HOC to vitronectin and stimulated ERK phosphorylation. All OPG-mediated effects could be prevented by RANKL antibodies or RANKL-siRNA transfection and MAPK inhibitor PD98059 reduced the stimulatory effect of OPG on integrin alphav expression. In acutely fractured vertebrae OPG and ALP mRNA expression was significantly increased compared to stable vertebral fractures. In conclusion, OPG exerts direct osteoanabolic effects on HOC metabolism via RANKL in addition to its well described role as decoy receptor for RANKL.

Prevalence, Risk Factors and Course of Osteoporosis in Patients with Crohn's Disease at a Tertiary Referral Center.

BACKGROUND: Patients with Crohn's disease are at increased risk for fractures due to low bone mineral density (BMD). Real-world data are necessary to optimize surveillance and treatment strategies. METHODS: Patients with Crohn's disease who underwent at least one dual-energy X-ray absorptiometry (DXA) scans were recruited. The primary study endpoints were (1) prevalence of osteoporosis, and (2) factors influencing changes of BMD. To identify potential risk factors for reduced BMD, Mann-Whitney U-test was used for ordinal and continuous variables and x²-tests for categorical variables. Results with p < 0.05 were included in a multivariable analysis. To identify potential factors influencing changes in BMD, a generalized linear mixed model was applied. RESULTS: 39.9% of the patients were diagnosed with normal BMD, 40.2% with osteopenia, and 19.8% with osteoporosis. The main risk factors for osteoporosis were low body mass index (BMI), previous bowel resections and male sex. The main risk factors for reduced BMD during further along the disease course were steroid use, history of immunomodulator treatment, female sex and decreased BMI. CONCLUSION: Low BMI, previous bowel resections and male sex were the main risk factors for the development of osteoporosis. Steroid use reduced BMD even under anti-inflammatory therapy, underlining that they should be used with great care in that patient group.

Mindful Sensation Seeking: An Examination of the Protective Influence of Selected Personality Traits on Risk Sport-Specific Stress.

Stress often has a negative influence on sports performance. Stress-induced decreases in performance can be especially disastrous for risk sports athletes, who often put their life at risk when practicing their sport. Therefore, it is of great importance to identify protective factors in stressful situations in risk sports. On average, risk sports athletes score extremely high on the personality trait sensation seeking. At the same time, theoretical considerations about dispositional mindfulness suggest that mindful athletes can handle stress more effectively. The main goal of this experiment is to examine the influence of sensation seeking and mindfulness on the stress response to a risk sport-specific stressor. To induce stress, 88 male students completed the Heidelberg Risk Sport-Specific Stress Test (HRSST) which utilizes fear of falling as the stressful event during a climbing exercise. Psychological (anxiety) and physiological (cortisol) responses were measured at multiple time points before and after the HRSST to determine the severity of the stress response. In reaction to the stressor, a significant increase in self-reported state anxiety, but no significant increase in cortisol were observed. The mindfulness subscale external observation correlated positively with anxiety in the climbing wall, sensation seeking and the anxiety scales after the jump correlated negatively and sensation seeking predicted anxiety subscales after the jump in hierarchical regression analyses. However, mindfulness did not predict anxiety measures. Neither sensation seeking nor mindfulness correlated significantly with cortisol levels. The results suggest that high sensation seekers perceive a risk sport-specific stressor as less stressful. The missing physiological response might be explained by the Cross-Stressor-Adaptation-Hypothesis and particularities of the sample. Good internal observers might be especially aware of their need of stimulation and new experiences, which in turn might explain the higher experience-seeking scores. Future studies should further examine the role of mindfulness in stressful situations and the interaction of its subscales with sensation seeking. The current experiment offers new possibilities for adjoining research fields at the interface between sports sciences, psychology and medicine: The findings can be transferred to high risk professions such as police officers, firefighters and military forces (e.g., for selection processes or for interventions).

Heidelberg Risk Sport-Specific Stress Test: A Paradigm to Investigate the Risk Sport-Specific Psycho-Physiological Arousal.

In risk sports with medium to high risks of injury (e.g., surfing, free solo climbing, wingsuit flying), athletes frequently find themselves in unexpected and threatening situations. Elevated psycho-physiological stress responses to these situations might have tremendous consequences for their performance as well as for their long-term health. To gain a better understanding of the psycho-physiological response to such events, innovative, externally valid and standardized stress induction protocols are needed. Therefore, the aim of this paper is to introduce and evaluate a risk sport-specific stress protocol, i.e., the Heidelberg Risk Sport-Specific Stress Test (HRSST), which utilizes fear of falling as the stressful event. Climbing novices were asked to climb up a 12 m high wall. Then, participants were requested to "jump into the rope", leading to a secured fall of about 3 m. This imposed physical danger assumed to elicit psycho-physiological responses. Self-reported state anxiety, salivary cortisol, and heart rate/heart rate variability were measured before, during, and after the HRSST. Results of four independent studies that investigated the psycho-physiological response to the HRSST in 214 participants were analyzed, leading to conclusions about the stressor's effectiveness. Results showed that self-reported state anxiety consistently increased after the HRSST in all four experiments (moderate to large effects). The results of the physiological indicators were inconclusive. Salivary cortisol significantly increased after the HRSST in one of four experiments (small effect sizes). Although heart rate significantly increased during the "jump in the rope" in experiment 1, heart rate variability significantly decreased after the HRSST in only one of three experiments (small effect sizes). Findings suggest that the HRSST is a valid method to induce risk sport-specific emotional stress, but effects on physiological stress markers were rather minor. To sum up, in case of appropriate sports climbing facilities, the HRSST appears to be a cost-efficient and promising stress induction protocol: It offers the possibility to investigate risk sport-specific stress responses and their underlying mechanisms in climbing novices. These findings may also find application in professions in which individuals are exposed to risky situations, such as police officers, medical first responders, firefighters and military personnel.

Effects of Coping-Related Traits and Psychophysiological Stress Responses on Police Recruits' Shooting Behavior in Reality-Based Scenarios.

Police officers are often required to perform under high-stress circumstances, in which optimal task performance is crucial for their and the bystanders' physical integrity. However, stress responses, particularly anxiety and increased cortisol levels, shift attention from goal-directed to stimulus-driven control, leaving police officers with poor shooting performance under stress. Cardiac vagal activity and coping-related traits (i.e., self-control, sensation seeking) might help individuals to maintain performance under stress. So far, only few studies have integrated coping-related traits, psychophysiological stress markers and occupationally meaningful measures of behavior to investigate police officers' work performance under stress. Therefore, the present study investigated 19 police recruits (M age = 22.84, SD = 3.30) undergoing a reality-based shooting scenario in two experimental conditions in a within-design: low stress (LS) against a non-threatening mannequin, and high stress (HS), involving physical threat by an opponent. Psychological (i.e., anxiety, mental effort) and physiological stress responses (i.e., salivary cortisol, alpha-amylase, cardiac vagal activity) as well as shooting accuracy were repeatedly assessed. It was hypothesized that under stress, police recruits would demonstrate elevated psychophysiological stress responses and impaired shooting performance. Elevated psychophysiological stress responses would negatively influence shooting performance, whereas self-control, sensation seeking and cardiac vagal activity would positively influence shooting performance. While recruits reported significantly higher anxiety and mental effort in the HS scenario, both scenarios elicited comparable physiological responses. Overall, shooting accuracy was low and did not significantly decrease in the HS scenario. Shooting performance was predicted by self-control in the LS scenario and by post-task cardiac vagal activity in the HS scenario. While increased anxiety hints at a successful stress manipulation, physiological responses suggest similar stress levels for both scenarios, diminishing potential behavioral differences between the scenarios. Performance efficiency decreased under stress, as indicated by increasing mental effort. Findings on self-control suggest that suppressing negative stress responses might lead to impaired goal-directed attention, resulting in performance decrements. For police research and training, high-realism scenarios afford an opportunity to investigate and experience psychophysiological stress responses.

Multiple prevalent fractures in relation to macroscopic bone architecture in patients with cystic fibrosis.

BACKGROUND: The relative risk for bone fractures in patients with cystic fibrosis (CF) and its relationship to macroscopic bone architecture assessed by pQCT and DXA are incompletely defined. METHODS: In a cross-sectional study of 43 CF patients (age, 17.8±6.2years), rate and location of fractures, bone mass, density, geometry, and strength of the radius as well as forearm muscle size were investigated. RESULTS: The fracture rate in CF was 9.2-fold higher compared to an age-matched German control population. The probability of remaining free of any fracture in CF patients at 25years was reduced to 39.8% compared to 84.6% in controls (P<0.001). Assessment of macroscopic bone architecture by DXA and pQCT allowed the differentiation of patients with multiple prevalent fractures with a high sensitivity (up to 100%) and specificity (up to 94.3%). CONCLUSIONS: Bone densitometry is a useful tool for noninvasive assessment of fracture risk in CF patients.

Diabetes Mellitus and Bone Metabolism.

Diabetes mellitus and bone metabolism affect mesenchymal tissues and have numerous epidemiological and pathophysiological associations in common. Diabetes mellitus affects bone metabolism and increases fracture risk. The pathophysiological mechanims how type 1 and type 2 diabetes impair bone metabolism and bone strength may differ which is outlined in this review. Direct metabolic effects in additon to centrally controlled endocrine loops exert suppressive effects on bone formation and may also stimulate bone Resorption. Decreased bone formation in combination with increased bone resorption strongly increases fracture risk.

Prenatal stress changes courtship vocalizations and bone mineral density in mice.

Stress during the prenatal period has various effects on social and sexual behavior in both human and animal offspring. The present study examines the effects of chronic restraint stress in the second vs third trimester in pregnancy and glucocorticoid receptor (GR) heterozygous mutation on C57BL/6N male offspring's vocal courtship behavior in adulthood by applying a novel analyzing method. Finally, corticosterone and testosterone levels as well as bone mineral density were measured. Prenatal stress in the third, but not in the second trimester caused a significant qualitative change in males' courtship vocalizations, independent of their GR genotype. Bone mineral density was decreased also by prenatal stress exclusively in the third trimester in GR mutant and wildtype mice and - in contrast to corticosterone and testosterone - highly correlated with courtship vocalizations. In Gr+/- males corticosterone serum levels were significantly increased in animals that had experienced prenatal stress in the third trimester. Testosterone serum levels were overall increased in Gr+/- males in comparison to wildtypes as a tendency - whereas prenatal stress had no influence. Prenatal stress alters adult males' courtship vocalizations exclusively when applied in the third trimester, with closely related changes in bone mineral density. Bone mineral density seems to reflect best the complex neuroendocrine mechanisms underlying the production of courtship vocalizations. Besides, we demonstrated for the first time elevated basal corticosterone levels in Gr+/- males after prenatal stress which suggests that the Gr+/- mouse model of depression might also serve as a model of prenatal stress in male offspring.

Osteointegration and Resorption of Intravertebral and Extravertebral Calcium Phosphate Cement.

STUDY DESIGN: Eleven patients with painful osteoporotic vertebral fractures who underwent kyphoplasty using calcium phosphate (CaP) cement were followed up for 1 week, 1, 2, and 3 years in a monocentric, nonrandomized, noncontrolled retrospective trial. OBJECTIVE: This study investigates long-term radiomorphologic features of intraosseous CaP cement implants and of extraosseous CaP cement leakages for up to 3 years after implantation by kyphoplasty. SUMMARY OF BACKGROUND DATA: Kyphoplasty is frequently used for the treatment of painful osteoporotic fractures. Of the materials available, CaP is frequently used as a filling material. Resorption of this material is frequently observed, although clinical outcome is comparable with other cements. METHODS: Kyphoplasty utilizing CaP cement was performed in 11 patients with painful osteoporotic vertebral fractures. All patients received a pharmacological antiosteoporosis treatment consisting of calcium, vitamin D, and a standard dose of oral bisphosphonates. Radiomorphologic measurements, pain, and mobility were assessed. RESULTS: Intraosseous and extraosseous CaP cement volumes decreased significantly over 3 years. However, vertebral stability as determined by a constant vertebral body height and the sagittal index was not impaired. Pain improved significantly 2 years after implantation and the mobility scores 1 year after kyphoplasty at least until the third year. CONCLUSIONS: Intravertebral CaP cement implants are resorbed slowly over time without jeopardizing stability and clinical outcomes most likely because of a slowly progressing osseous replacement. Extraosseous CaP cement material because of leakages during the kyphoplasty procedure is almost completely resorbed as early as 2 years after the leakage occurred. Therefore, CaP cement is an important alternative to PMMA-based cement materials utilized for kyphoplasty of osteoporotic vertebral fractures.

[Therapeutic management of acromegaly]. / Therapeutisches Management bei der Akromegalie.

BACKGROUND: Only 60% of the patients with acromegaly are biochemically cured (growth hormone [GH] nadir < 1.0 microg/l after an oral glucose load, normalized age- and gender-matched insulin-like growth factor-1 [IGF-1] levels) after transsphenoidal surgery of the pituitary gland. In the absence of a remission there are effective pharmacological treatment regimens available which are able to lower GH and IGF-1 serum levels. THERAPEUTIC STRATEGIES: Somatostatin analogs, a GH receptor antagonist and dopamine agonists have been shown to alleviate the comorbid features and to normalize GH and IGF-1 levels. CASE REPORTS: In this overview six case reports are presented to highlight the current pharmacological treatment options and to propose an algorithm for the clinical routine in patients with persisting acromegaly. CONCLUSION: Transsphenoidal surgery is the treatment of choice for the initial management of acromegaly. In the absence of a remission there are effective pharmacological treatment regimens available among which somatostatin analogs are recommended as the first-line treatment.

Treatment of painful vertebral fractures by kyphoplasty in patients with primary osteoporosis: a prospective nonrandomized controlled study.

UNLABELLED: This study investigates the effects of kyphoplasty on pain and mobility in patients with osteoporosis and painful vertebral fractures compared with conventional medical management. INTRODUCTION: Pharmacological treatment of patients with primary osteoporosis does not prevent pain and impaired activity of patients with painful vertebral fractures. Therefore, we evaluated the clinical outcome after kyphoplasty in patients with vertebral fractures and associated chronic pain for >12 months. MATERIALS AND METHODS: Sixty patients with primary osteoporosis and painful vertebral fractures presenting for >12 months were included in this prospective, nonrandomized controlled study. Twenty-four hours before performing kyphoplasty, the patients self-determined their inclusion into the kyphoplasty or control group so that 40 patients were treated with kyphoplasty, whereas 20 served as controls. This study assessed changes in radiomorphology, pain visual analog scale (VAS) score, daily activities (European Vertebral Osteoporosis Study [EVOS] score), number of new vertebral fractures, and health care use. Outcomes were assessed before treatment and at 3 and 6 months of follow-up. All patients received standard medical treatment (1g calcium, 1000 IE vitamin D(3), standard dose of oral aminobisphosphonate, pain medication, physical therapy). RESULTS: Kyphoplasty increased midline vertebral height of the treated vertebral bodies by 12.1%, whereas in the control group, vertebral height decreased by 8.2% (p = 0.001). Augmentation and internal stabilization by kyphoplasty resulted in a reduction of back pain. VAS pain scores improved in the kyphoplasty group from 26.2 +/- 2 to 44.2 +/- 3.3 (SD; p = 0.007) and in the control group from 33.6 +/- 4.1 to 35.6 +/- 4.1 (not significant), whereas the EVOS score increased in the kyphoplasty group from 43.8 +/- 2.4 to 54.5 +/- 2.7 (p = 0.031) and in the control group from 39.8 +/- 4.5 to 43.8 +/- 4.6 (not significant). The number of back pain-related doctor visits within the 6-month follow-up period decreased significantly after kyphoplasty compared with controls: mean of 3.3 visits/patient in the kyphoplasty group and a mean of 8.6 visits/patient in the control group (p = 0.0147). CONCLUSIONS: The results of this study show significantly increased vertebral height, reduced pain, and improved mobility in patients after kyphoplasty. Kyphoplasty performed in appropriately selected osteoporotic patients with painful vertebral fractures is a promising addition to current medical treatment.

Elevated plasma endothelin-1 levels in diabetes mellitus.

BACKGROUND: This study compares plasma endothelin-1 (ET-1) levels in patients with diabetes mellitus or hypertension with healthy controls, and investigates whether ET-1 levels are correlated with glycemic control, metabolic parameters, and vascular complications. METHODS: The study population consisted of 103 patients with type 1 diabetes, 124 patients with type 2 diabetes, 35 hypertensive patients without diabetes mellitus, and 99 controls. RESULTS: Plasma ET-1 concentrations were significantly higher in patients with type 1 diabetes (0.28 +/- 0.34 fmol/mL, P =.001), type 2 diabetes (0.31 +/- 0.32 fmol/mL, P <.0001), and hypertension (0.35 +/- 0.26 fmol/mL, P <.0001) compared to controls (0.08 +/- 0.13 fmol/mL). Diabetic patients taking angiotensin converting enzyme (ACE) inhibitors had significantly lower plasma ET-1 levels than patients without (0.22 +/- 0.20 fmol/mL v 0.38 +/- 0.39 fmol/mL, P =.029). There were significant associations between ET-1 levels and age (r = 0.38, P <.05) and systolic blood pressure (BP) (r = 0.27, P <.05) in healthy controls. In diabetes we found only nonsignificant associations between ET-1 levels and age or vascular complications and a weak association between plasma ET-1 levels and glycemic control. CONCLUSIONS: Patients with diabetes or hypertension have elevated ET-1 levels, but do not exhibit positive correlations between ET-1 levels and BP, which was observed in healthy controls. Increased ET-1 levels do not induce hypertension in diabetes, but were lower in diabetic patients taking ACE inhibitors compared to those without ACE inhibitors. There is no significant association between ET-1 levels and vascular complications. These findings suggest that the plasma ET-1 level is not a marker of endothelial dysfunction but changes in plasma ET-1 levels may precede vascular complications associated with hypertension and diabetes.