Understanding the mechanisms underlying cognitive control in psychosis.

BACKGROUND: Cognitive control (CC) involves a top-down mechanism to flexibly respond to complex stimuli and is impaired in schizophrenia. METHODS: This study investigated the impact of increasing complexity of CC processing in 140 subjects with psychosis and 39 healthy adults, with assessments of behavioral performance, neural regions of interest and symptom severity. RESULTS: The lowest level of CC (Stroop task) was impaired in all patients; the intermediate level of CC (Faces task) with explicit emotional information was most impaired in patients with first episode psychosis. Patients showed activation of distinct neural CC and reward networks, but iterative learning based on the higher-order of CC during the trust game, was most impaired in chronic schizophrenia. Subjects with first episode psychosis, and patients with lower symptom load, demonstrate flexibility of the CC network to facilitate learning, which appeared compromised in the more chronic stages of schizophrenia. CONCLUSION: These data suggest optimal windows for opportunities to introduce therapeutic interventions to improve CC.

Sustained release of locally delivered celecoxib provides pain relief for osteoarthritis: a proof of concept in dog patients.

OBJECTIVE: Drug delivery platforms that allow for gradual drug release after intra-articular administration have become of much interest as a treatment strategy for osteoarthritis (OA). The aim of this study was to investigate the safety and efficacy of an intra-articular sustained release formulation containing celecoxib (CXB), a cyclooxygenase-2 (COX-2) selective inhibitor. METHODS: Amino acid-based polyesteramide microspheres (PEAMs), a biodegradable and non-toxic platform, were loaded with CXB and employed in two in vivo models of arthritis: an acute inflammatory arthritis model in rats (n = 12), and a randomized controlled study in chronic OA dog patients (n = 30). In parallel, the bioactivity of sustained release of CXB was evaluated in monolayer cultures of primary dog chondrocytes under inflammatory conditions. RESULTS: Sustained release of CXB did not alleviate acute arthritis signs in the rat arthritis model, based on pain measurements and synovitis severity. However, in OA dog patients, sustained release of CXB improved limb function as objective parameter of pain and quality of life based on gait analysis and owner questionnaires. It also decreased pain medication dependency over a 2-month period and caused no adverse effects. Prostaglandin E2 levels, a marker for inflammation, were lower in the synovial fluid of CXB-treated dog OA patients and in CXB-treated cultured dog chondrocytes. CONCLUSION: These results show that local sustained release of CXB is less suitable to treat acute inflammation in arthritic joints, while safe and effective in treating pain in chronic OA in dogs.

A new semi-orthotopic bone defect model for cell and biomaterial testing in regenerative medicine.

In recent decades, an increasing number of tissue engineered bone grafts have been developed. However, expensive and laborious screenings in vivo are necessary to assess the safety and efficacy of their formulations. Rodents are the first choice for initial in vivo screens but their size limits the dimensions and number of the bone grafts that can be tested in orthotopic locations. Here, we report the development of a refined murine subcutaneous model for semi-orthotopic bone formation that allows the testing of up to four grafts per mouse one order of magnitude greater in volume than currently possible in mice. Crucially, these defects are also "critical size" and unable to heal within the timeframe of the study without intervention. The model is based on four bovine bone implants, ring-shaped, where the bone healing potential of distinct grafts can be evaluated in vivo. In this study we demonstrate that promotion and prevention of ossification can be assessed in our model. For this, we used a semi-automatic algorithm for longitudinal micro-CT image registration followed by histological analyses. Taken together, our data supports that this model is suitable as a platform for the real-time screening of bone formation, and provides the possibility to study bone resorption, osseointegration and vascularisation.

No added value for Computer-Assisted surgery to improve femoral component positioning and Patient Reported Outcomes in Hip Resurfacing Arthroplasty; a multi-center randomized controlled trial.

BACKGROUND: Computer Assisted Surgery (CAS) has proven to improve the accuracy in several orthopedic procedures. Therefore we used this technique to evaluate femoral component positioning in Hip Resurfacing Arthroplasty (HRA). The aim of this study was to evaluate imageless CAS compared to manually implanted femoral components and subsequently evaluates Patient Related Outcome Measures (PROMs). We hypothesized that the use of CAS optimizes the position of the femoral component and improves PROMs. METHODS: This is a multicenter, single-blinded, randomized, controlled trial of two groups. In the CAS group guiding of the femoral component was done with imageless navigation. In the Conventional (control) group the femoral component was placed manually according to the preplanned position. The primary outcome measure consists of a maximum of 3 degrees difference between the postoperative Stem Shaft Angle (SSA) and preplanned SSA. Secondary outcome measures consist of the Hip disability and Osteoarthritis Outcome Scale (HOOS), the Harris Hip Score (HHS) and Visual Analogue Scale (VAS) pain score. RESULTS: A total of 122 patients were randomized, 61 in the CAS group and 61 in the conventional group. There was no significant differences in accuracy of femoral implant position. The mean difference between the postoperative- and preplanned SSA was - 2.26 and - 1.75 degrees (more varus) respectively in the CAS and Conventional group. After surgery both groups show significant improvement in all PROMs compared to the baseline measurements, with no significant differences between the groups. CONCLUSION: Our cohort indicates no benefit for the use of CAS in accuracy of placement of the femoral component in HRA compared to manual implantation. There are no clinical differences in PROMs after 1 year follow up. This study showed no added value and no justification for the use of CAS in femoral component positioning in HRA. TRIAL REGISTRATION: This trial is registered at ClinicalTrails.gov ( https://clinicaltrials.gov/ ) on the 25th of October 2006: NCT00391937. LEVEL OF INCIDENCE: Level IIb, multicenter randomized controlled trial.

Strategies for managing multi-patient 3D mass spectrometry imaging data.

Mass spectrometry imaging (MSI) has emerged as a powerful tool in biomedical research to reveal the localization of a broad scale of compounds ranging from metabolites to proteins in diseased tissues, such as malignant tumors. MSI is most commonly used for the two-dimensional imaging of tissues from multiple patients or for the three-dimensional (3D) imaging of tissue from a single patient. These applications are potentially introducing a sampling bias on a sample or patient level, respectively. The aim of this study is therefore to investigate the consequences of sampling bias on sample representativeness and on the precision of biomarker discovery for histological grading of human bladder cancers by MSI. We therefore submitted formalin-fixed paraffin-embedded tissues from 14 bladder cancer patients with varying histological grades to 3D analysis by matrix-assisted laser desorption/ionization (MALDI) MSI. We found that, after removing 20% of the data based on novel outlier detection routines for 3D-MSI data based on the evaluation of digestion efficacy and z-directed regression, on average 33% of a sample has to be measured in order to obtain sufficient coverage of the existing biological variance within a tissue sample. SIGNIFICANCE: In this study, 3D MALDI-MSI is applied for the first time on a cohort of bladder cancer patients using formalin-fixed paraffin-embedded (FFPE) tissue of bladder cancer resections. This work portrays the reproducibility that can be achieved when employing an optimized sample preparation and subsequent data evaluation approach. Our data shows the influence of sampling bias on the variability of the results, especially for a small patient cohort. Furthermore, the presented data analysis workflow can be used by others as a 3D FFPE data-analysis pipeline working on multi-patient 3D-MSI studies.

Intradiscal delivery of celecoxib-loaded microspheres restores intervertebral disc integrity in a preclinical canine model.

Low back pain, related to degeneration of the intervertebral disc (IVD), affects millions of people worldwide. Clinical studies using oral cyclooxygenase-2 (COX-2) inhibitors have shown beneficial effects, although side-effects were reported. Therefore, intradiscal delivery of nonsteroidal anti-inflammatory drugs can be an alternative treatment strategy to halt degeneration and address IVD-related pain. In the present study, the controlled release and biologic potency of celecoxib, a selective COX-2 inhibitor, from polyesteramide microspheres was investigated in vitro. In addition, safety and efficacy of injection of celecoxib-loaded microspheres were evaluated in vivo in a canine IVD degeneration model. In vitro, a sustained release of celecoxib was noted for over 28 days resulting in sustained inhibition of inflammation, as indicated by decreased prostaglandin E2 (PGE2) production, and anti-catabolic effects in nucleus pulposus (NP) cells from degenerated IVDs on qPCR. In vivo, there was no evidence of adverse effects on computed tomography and magnetic resonance imaging or macroscopic evaluation of IVDs. Local and sustained delivery of celecoxib prevented progression of IVD degeneration corroborated by MRI, histology, and measurement of NP proteoglycan content. Furthermore, it seemed to harness inflammation as indicated by decreased PGE2 tissue levels and decreased neuronal growth factor immunopositivity, providing indirect evidence that local delivery of a COX-2 inhibitor could also address pain related to IVD degeneration. In conclusion, intradiscal controlled release of celecoxib from polyesteramide microspheres prevented progression of IVD degeneration both in vitro and in vivo. Follow-up studies are warranted to determine the clinical efficacy of celecoxib-loaded PEAMs in chronic back pain.

Controlled release of celecoxib inhibits inflammation, bone cysts and osteophyte formation in a preclinical model of osteoarthritis.

Major hallmarks of osteoarthritis (OA) are cartilage degeneration, inflammation and osteophyte formation. COX-2 inhibitors counteract inflammation-related pain, but their prolonged oral use entails the risk for side effects. Local and prolonged administration in biocompatible and degradable drug delivery biomaterials could offer an efficient and safe treatment for the long-term management of OA symptoms. Therefore, we evaluated the disease-modifying effects and the optimal dose of polyesteramide microspheres delivering the COX-2 inhibitor celecoxib in a rat OA model. Four weeks after OA induction by anterior cruciate ligament transection and partial medial meniscectomy, 8-week-old female rats (n = 6/group) were injected intra-articular with celecoxib-loaded microspheres at three dosages (0.03, 0.23 or 0.39 mg). Unloaded microspheres served as control. During the 16-week follow-up, static weight bearing and plasma celecoxib concentrations were monitored. Post-mortem, micro-computed tomography and knee joint histology determined progression of synovitis, osteophyte formation, subchondral bone changes, and cartilage integrity. Systemic celecoxib levels were below the detection limit 6 days upon delivery. Systemic and local adverse effects were absent. Local delivery of celecoxib reduced the formation of osteophytes, subchondral sclerosis, bone cysts and calcified loose bodies, and reduced synovial inflammation, while cartilage histology was unaffected. Even though the effects on pain could not be evualated directly in the current model, our results suggest the application of celecoxib-loaded microspheres holds promise as novel, safe and effective treatment for inflammation and pain in OA.

Value of Quantitative Collateral Scoring on CT Angiography in Patients with Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Many studies have emphasized the relevance of collateral flow in patients presenting with acute ischemic stroke. Our aim was to evaluate the relationship of the quantitative collateral score on baseline CTA with the outcome of patients with acute ischemic stroke and test whether the timing of the CTA acquisition influences this relationship. MATERIALS AND METHODS: From the Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) data base, all baseline thin-slice CTA images of patients with acute ischemic stroke with intracranial large-vessel occlusion were retrospectively collected. The quantitative collateral score was calculated as the ratio of the vascular appearance of both hemispheres and was compared with the visual collateral score. Primary outcomes were 90-day mRS score and follow-up infarct volume. The relation with outcome and the association with treatment effect were estimated. The influence of the CTA acquisition phase on the relation of collateral scores with outcome was determined. RESULTS: A total of 442 patients were included. The quantitative collateral score strongly correlated with the visual collateral score (ρ = 0.75) and was an independent predictor of mRS (adjusted odds ratio = 0.81; 95% CI, .77-.86) and follow-up infarct volume (exponent ß = 0.88; P < .001) per 10% increase. The quantitative collateral score showed areas under the curve of 0.71 and 0.69 for predicting functional independence (mRS 0-2) and follow-up infarct volume of >90 mL, respectively. We found significant interaction of the quantitative collateral score with the endovascular therapy effect in unadjusted analysis on the full ordinal mRS scale (P = .048) and on functional independence (P = .049). Modification of the quantitative collateral score by acquisition phase on outcome was significant (mRS: P = .004; follow-up infarct volume: P < .001) in adjusted analysis. CONCLUSIONS: Automated quantitative collateral scoring in patients with acute ischemic stroke is a reliable and user-independent measure of the collateral capacity on baseline CTA and has the potential to augment the triage of patients with acute stroke for endovascular therapy.

[Fatal intoxication with nicotine for e-cigarette]. / Fatale intoxicatie met nicotine voor e-sigaret.

BACKGROUND: Since the introduction of the electronic e-cigarette a few years ago, its use has greatly increased. The liquid formulations used in these e-cigarettes contain nicotine in high concentrations; ingestion of these liquids can be fatal. CASE DESCRIPTION: A 42-year-old male was admitted to the Intensive Care ward due to cardiac arrest. The patient had ingested highly concentrated liquid nicotine, originating from a vial with liquid for e-cigarettes. When the ambulance personnel found the patient he did not have a pulse; following CPR and administration of adrenaline his pulse returned. Upon admission, the plasma nicotine level was high at 3.0 mg/l (reference values for a smoker are 0.01-0.05 mg/l) and the patient's neurological function was poor. The patient was treated symptomatically, but eventually died of a postanoxic encephalopathy. CONCLUSION: Nicotine e-liquids are highly concentrated. Intentional ingestion can lead to toxic levels of nicotine which are associated with cardiac arrhythmias or arrest. Because even a few millilitres can be lethal, nicotine intoxication due to e-liquid ingestion should be considered potentially life-threatening.

Comparison of CTA- and DSA-Based Collateral Flow Assessment in Patients with Anterior Circulation Stroke.

BACKGROUND AND PURPOSE: Collateral flow is associated with clinical outcome after acute ischemic stroke and may serve as a parameter for patient selection for intra-arterial therapy. In clinical trials, DSA and CTA are 2 imaging modalities commonly used to assess collateral flow. We aimed to determine the agreement between collateral flow assessment on CTA and DSA and their respective associations with clinical outcome. MATERIALS AND METHODS: Patients randomized in MR CLEAN with middle cerebral artery occlusion and both baseline CTA images and complete DSA runs were included. Collateral flow on CTA and DSA was graded 0 (absent) to 3 (good). Quadratic weighted κ statistics determined agreement between both methods. The association of both modalities with mRS at 90 days was assessed. Also, association between the dichotomized collateral score and mRS 0-2 (functional independence) was ascertained. RESULTS: Of 45 patients with evaluable imaging data, collateral flow was graded on CTA as 0, 1, 2, 3 for 3, 10, 20, and 12 patients, respectively, and on DSA for 12, 17, 10, and 6 patients, respectively. The κ-value was 0.24 (95% CI, 0.16-0.32). The overall proportion of agreement was 24% (95% CI, 0.12-0.38). The adjusted odds ratio for favorable outcome on mRS was 2.27 and 1.29 for CTA and DSA, respectively. The relationship between the dichotomized collateral score and mRS 0-2 was significant for CTA (P = .01), but not for DSA (P = .77). CONCLUSIONS: Commonly applied collateral flow assessment on CTA and DSA showed large differences, indicating that these techniques are not interchangeable. CTA was significantly associated with mRS at 90 days, whereas DSA was not.

Generalized versus patient-specific inflow boundary conditions in computational fluid dynamics simulations of cerebral aneurysmal hemodynamics.

BACKGROUND AND PURPOSE: Attempts have been made to associate intracranial aneurysmal hemodynamics with aneurysm growth and rupture status. Hemodynamics in aneurysms is traditionally determined with computational fluid dynamics by using generalized inflow boundary conditions in a parent artery. Recently, patient-specific inflow boundary conditions are being implemented more frequently. Our purpose was to compare intracranial aneurysm hemodynamics based on generalized versus patient-specific inflow boundary conditions. MATERIALS AND METHODS: For 36 patients, geometric models of aneurysms were determined by using 3D rotational angiography. 2D phase-contrast MR imaging velocity measurements of the parent artery were performed. Computational fluid dynamics simulations were performed twice: once by using patient-specific phase-contrast MR imaging velocity profiles and once by using generalized Womersley profiles as inflow boundary conditions. Resulting mean and maximum wall shear stress and oscillatory shear index values were analyzed, and hemodynamic characteristics were qualitatively compared. RESULTS: Quantitative analysis showed statistically significant differences for mean and maximum wall shear stress values between both inflow boundary conditions (P < .001). Qualitative assessment of hemodynamic characteristics showed differences in 21 cases: high wall shear stress location (n = 8), deflection location (n = 3), lobulation wall shear stress (n = 12), and/or vortex and inflow jet stability (n = 9). The latter showed more instability for the generalized inflow boundary conditions in 7 of 9 patients. CONCLUSIONS: Using generalized and patient-specific inflow boundary conditions for computational fluid dynamics results in different wall shear stress magnitudes and hemodynamic characteristics. Generalized inflow boundary conditions result in more vortices and inflow jet instabilities. This study emphasizes the necessity of patient-specific inflow boundary conditions for calculation of hemodynamics in cerebral aneurysms by using computational fluid dynamics techniques.

Markers of bone turnover in Gaucher disease: modeling the evolution of bone disease.

CONTEXT: Gaucher disease (GD) is a lysosomal storage disorder characterized by abundant presence of macrophages. Bone complications and low bone density are believed to arise from enhanced bone resorption mediated through macrophage-derived factors. OBJECTIVE: The objective of the study was to investigate the relationship between bone turnover and bone complications in GD. DESIGN: This was a retrospective cohort study and review of the literature. PATIENTS: Forty adult type I GD patients were included in the study. OUTCOME MEASURES: Levels of the bone-resorption marker, type 1 collagen C-terminal telopeptide, and two bone-formation markers, N-terminal propeptide of type 1 procollagen and osteocalcin, were investigated in relation to clinical bone disease, measures of overall disease severity, and imaging data representing bone marrow infiltration. RESULTS: Osteocalcin was decreased in 50% of our patients (median 0.35 nmol/liter, normal 0.4-4.0), indicating a decrease of bone formation. Type 1 collagen C-terminal telopeptide and N-terminal propeptide of type 1 procollagen were within the normal range for most patients. Osteocalcin concentration was negatively correlated to measures of overall disease severity and positively correlated with imaging data (correlation coefficient 0.423; P = 0.025), suggesting a relation with disease severity. A review of the literature revealed variable outcomes on bone resorption markers but more consistent abnormalities in bone formation markers. Two of three reports conclude that bone-formation parameters increase in response to enzyme therapy, but none describes an effect on bone-resorption markers. CONCLUSIONS: In contrast to earlier hypotheses, we propose that in GD patients, primarily a decrease in bone formation causes an imbalance in bone remodeling.

Pseudocyst formation in retroperitoneal fibrosis relapse.

We describe a 45-year-old male patient with recurrent retroperitoneal fibrosis (RPF), in whom a pseudocyst in the peri-aortic fibrotic mantle was diagnosed. Without any intervention other than oral treatment with tamoxifen, the pseudocyst showed significant regression. Although rare, pseudocyst formation may sometimes appear in RPF and may mimic other benign and malignant conditions. This is the first paper to describe pseudocyst formation in an RPF relapse.

(18)F-fluorodeoxyglucose position emission tomography (FDG-PET) for monitoring disease activity and treatment response in idiopathic retroperitoneal fibrosis.

OBJECTIVE: To evaluate the value of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in monitoring disease activity and predicting treatment response in idiopathic retroperitoneal fibrosis (iRPF). PATIENTS AND METHODS: This prospective study was approved by the institutional review board. Informed consent was obtained from all patients. Twenty-six patients with iRPF receiving tamoxifen monotherapy underwent repeated FDG-PET (baseline and, if positive, at 3 months) and computed tomographic (CT) scanning (baseline, 4 and 8 months). Maximal RPF mass thickness in 3 different view directions was measured on each CT scan; FDG-uptake was semi-quantified using a visual 4-point scale. Initial and follow-up PET scan results were correlated with clinical, laboratory and CT scan follow-up data. Treatment outcome was the aggregate measure of clinical, laboratory and CT-documented response to tamoxifen. RESULTS: FDG-PET was positive in 20 patients. Patients with positive PET scan result had higher C-reactive protein level (P=0.02) and larger mass size (P=0.01) compared with patients with negative PET scan result. Visual PET score correlated with C-reactive protein level (P=0.002) and CT-documented mass thickness (P=0.04). Visual PET score decreased following treatment (P<0.01). This decrease correlated with decrease in ESR (P<0.001) but not with CT-documented mass regression. Positive predicting value (PPV) of initial positive PET scan result was 0.63; PPV of negative follow-up PET scan result in patients with initial positive PET scan result was 0.66. CONCLUSION: FDG-PET is valuable in detecting (recurrent) disease activity. Short-term follow-up with FDG-PET cannot be routinely recommended for the therapeutic evaluation of RPF disease in tamoxifen-treated patients.

Type II and VI collagen in nasal and articular cartilage and the effect of IL-1alpha on the distribution of these collagens.

The distribution of type II and VI collagen was immunocytochemically investigated in bovine articular and nasal cartilage. Cartilage explants were used either fresh or cultured for up to 4 weeks with or without interleukin 1alpha (IL-1alpha). Sections of the explants were incubated with antibodies for both types of collagen. Microscopic analyses revealed that type II collagen was preferentially localized in the interchondron matrix whereas type VI collagen was primarily found in the direct vicinity of the chondrocytes. Treatment of the sections with hyaluronidase greatly enhanced the signal for both types of collagen. Also in sections of explants cultured with IL-1alpha a higher level of labeling of the collagens was found. This was apparent without any pre-treatment with hyaluronidase. Under the influence of IL-1alpha the area positive for type VI collagen that surrounded the chondrocytes broadened. Although the two collagens in both types of cartilage were distributed similarly, a remarkable difference was the higher degree of staining of type VI collagen in articular cartilage. Concomitantly we noted that digestion of this type of cartilage hardly occurred in the presence of IL-1alpha whereas nasal cartilage was almost completely degraded within 18 days of culture. Since type VI collagen is known to be relatively resistant to proteolysis we speculate that the higher level of type VI collagen in articular cartilage is important in protecting cartilage from digestion.

Idiopathic retroperitoneal fibrosis: prospective evaluation of incidence and clinicoradiologic presentation.

Retroperitoneal fibrosis (RPF) is a rare disorder of unknown etiology. Its incidence is unknown, and the insidious and nonspecific nature of symptoms may contribute to considerable diagnostic delay. We conducted the current study to assess the incidence and clinicoradiologic characteristics of idiopathic RPF. For this, we evaluated prospectively 53 consecutive patients with a diagnosis of idiopathic RPF at our tertiary care referral center from April 1998 through January 2008.Calculated annual incidence of RPF was 1.3/100,000 inhabitants. Mean age was 64 +/- 11.1 (SD) yr; male-female ratio was 3.3:1.0. Median duration of symptoms was 6.0 mo (IQR 3.0-12.0). Abdominal, flank, and/or back pain and discomfort were the major symptoms, with visual analogue scale scores of 49 +/- 27.2 mm and 43 +/- 29.4 mm for pain and discomfort, respectively. Female patients had higher erythrocyte sedimentation rate (ESR), higher white blood cell count, and lower hemoglobin content than male patients at presentation. Computed tomography-documented maximal mass thickness amounted to 35 +/- 16.6 mm; craniocaudal length amounted to 137 +/- 48.8 mm. RPF mass extension up to or above the level of the renal vessels was noted in 3 patients (6%). Six patients (11%) presented with atypical RPF localization and/or bulky mass. Localized lymphadenopathy adjacent to the RPF mass was observed frequently (25%). Patients with hydronephrosis (56%) presented earlier than patients without hydronephrosis, with higher creatinine and greater mass thickness but similar pain severity. Patients were typically at high cardiovascular risk with increased-often aneurysmal-infrarenal aortic diameter (25.0 mm, IQR 22.0-30.0). RPF mass distribution was similar in patients with or without aneurysmal dilation. Occupational asbestos exposure (20%) and asbestos-related pleural changes (17%) were frequent among males. Previous or concurrent chronic inflammatory disease and/or autoimmune disease was noted in 8 patients (15%). Multivariate analysis revealed an independent association of ESR values with severity of pain and discomfort. Smoking was independently associated with infrarenal aortic diameter.In summary, annual RPF incidence is higher than previously assumed. Age at diagnosis and male-female ratio seem to have changed over time. RPF typically affects patients at high cardiovascular risk, including increased aortic diameter. Clinical presentation is influenced by sex, severity of inflammation and presence of hydronephrosis. Prolonged asbestos exposure and asbestos-related pleural changes were frequent among males. Localized lymphadenopathy adjacent to the RPF mass occurs frequently and should not confuse RPF diagnosis.

High prevalence of hypogonadotropic hypogonadism in men referred for obesity treatment.

BACKGROUND: Obesity can be associated with biochemical evidence of isolated hypogonadotropic hypogonadism (IHH) in men. Prevalence and severity of IHH in obese men are not exactly known. OBJECTIVE: To assess the prevalence of IHH in obese men. DESIGN AND SUBJECTS: Cross-sectional study of 160 obese men, BMI >30 kg/m2, who applied for medical or surgical treatment of obesity in a general teaching hospital. MAIN OUTCOME MEASURES: Total and calculated free testosterone (TT and FT) in relation to body mass index (BMI). RESULTS: Mean age of the study population was 43.3 +/- 0.8 years (mean +/- SEM), BMI ranged from 30.0 to 65.7 kg/m2. TT and FT levels were inversely related to BMI (-0.48, p<0.0001). Total testosterone was subnormal in 57.5% and free testosterone in 35.6% of the subjects. The group of men with IHH was more obese, had higher Hba IC levels and had a 2.6 higher risk for cardiovascular disease. Decreased libido and erectile dysfunction were 7.1 and 6.7 times as common in IHH than in eugonadal obese men. CONCLUSION: Reduced T levels, well into the hypogonadal range, are common in male obesity. Assessment of its clinical implications, and a search for the best mode of treatment are warranted.

Decision making in childbirth: the influence of traditional structures in a Ghanaian village.

BACKGROUND: The regional health administration of the Brong-Ahafo Region in Ghana identified that although informed about the advantages of both aspects of care, pregnant women made use of antenatal services but not of the supervised delivery. Quantitative studies have identified economic factors that influence the decisions of pregnant women. AIM: To describe and understand the traditional structures of childbirth in Kwame Danso/Ghana and to explore why the pregnant women do not make use of supervised deliveries in the modern institutions. METHODS: A mini-ethnographic study, using participant observation and ethnographic interviews. FINDINGS: Cultural and social factors have a significant influence on the decisions related to childbirth. One of the most important factors identified was that the responsible persons for decisions related to a delivery were the older female relatives, rather than the mothers themselves. Older females used rational judgements to weigh up the possibilities of risks, interests and advantages related to their cultural, spiritual and social system. Other factors were staff behaviour that was characterized as unfriendly and lacking for respect as to the living conditions and thinking of the pregnant women in the village. CONCLUSIONS: Ethnographic research provided an understanding of traditional structures that have an influence on the decisions and behaviour of the community related to childbirth. Appreciation of these structures enabled health promotion and structured health services to be delivered in a more culturally appropriate way.

Tuberculin skin test: estimation of positive and negative predictive values from routine data.

OBJECTIVE: To estimate, using routinely available data, the predictive values of tuberculin testing with 2TU RT23 for detection of latent tuberculosis infection (LTBI) in the Dutch population as a basis for recommendations on cut-off values at various levels of infection prevalence. DESIGN: Smoothed distributions of TST reactions among 312 tuberculosis patients and 2848 healthy non-BCG-vaccinated persons were used to estimate the sensitivity and specificity at various cut-off values. RESULTS: Sensitivity was 98.9% at 5 mm, 95.4% at 10 mm and 79.8% at 15 mm cut-off. Specificity with the corresponding cut-offs was 95.3%, 96.3% and 97.1% before and 98.0%, 98.8% and 99.6% after adjustment for presumed LTBI. At 10 mm, the positive predictive value (PPV) was > 75% if the infection prevalence in the tested population was at least 10%, but strongly declined with lower prevalences. For lower prevalences a cut-off of 15 mm was proposed, as this results in a higher PPV without greatly affecting the negative predictive value. CONCLUSION: Estimation of the predictive values of the TST from routine data can be useful for establishing cut-off values for detection of LTBI in different populations with different tuberculin preparations.