Exercise increases myocardial free fatty acid oxidation in subjects with metabolic dysfunction-associated fatty liver disease.

BACKGROUND AND AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) is associated with dyslipidemia and may promote cardiac lipotoxicity. Myocardial free fatty acids (FFA) oxidation (MOFFA) is normal in pre-diabetes, but reduced in heart failure. We hypothesized that during exercise MOFFA, very low-density lipoprotein triglycerides (VLDL-TG) secretion, hepatic FFA utilization, and lactate production differ among obese subjects with and without MAFLD. METHODS: Nine obese subjects with MAFLD and 8 matched subjects without MAFLD (Control) without a history of heart failure and cardiovascular disease were compared before and after 90-min exercise at 50% Peak oxygen consumption. Basal and exercise induced cardiac and hepatic FFA oxidation, uptake and re-esterification and VLDL-TG secretion were measured using [11C]palmitate positron-emission tomography and [1-14C]VLDL-TG. RESULTS: In the heart, increased MOFFA was observed after exercise in MAFLD, whereas MOFFA decreased in Control (basal vs exercise, MAFLD: 4.1 (0.8) vs 4.8 (0.8) µmol·100 ml-1 min-1; Control: 4.9 (1.8) vs 4.0 (1.1); µmol·100 ml-1 min-1, mean (SD), p < 0.048). Hepatic FFA fluxes were significantly lower in MAFLD than Control and increased ≈ two-fold in both groups. VLDL-TG secretion was 50% greater in MAFLD at rest and similarly suppressed during exercise. Plasma lactate increased significantly less in MAFLD than Control during exercise. CONCLUSIONS: Using robust tracer-techniques we found that obese subjects with MAFLD do not downregulate MOFFA during exercise compared to Control, possibly due to diminished lactate supply. Hepatic FFA fluxes are significantly lower in MAFLD than Control, but increase similarly with exercise. VLDL-TG export remains greater in MAFLD compared to Control. Basal and post-exercise myocardial and hepatic FFA, VLDL-TG and lactate metabolism is abnormal in subjects with MAFLD compared to Control.

Prevalence and risk factors related to haloperidol use for delirium in adult intensive care patients: the multinational AID-ICU inception cohort study.

PURPOSE: We assessed the prevalence and variables associated with haloperidol use for delirium in ICU patients and explored any associations of haloperidol use with 90-day mortality. METHODS: All acutely admitted, adult ICU patients were screened during a 2-week inception period. We followed the patient throughout their ICU stay and assessed 90-day mortality. We assessed patients and their variables in the first 24 and 72 h in ICU and studied their association together with that of ICU characteristics with haloperidol use. RESULTS: We included 1260 patients from 99 ICUs in 13 countries. Delirium occurred in 314/1260 patients [25% (95% confidence interval 23-27)] of whom 145 received haloperidol [46% (41-52)]. Other interventions for delirium were benzodiazepines in 36% (31-42), dexmedetomidine in 21% (17-26), quetiapine in 19% (14-23) and olanzapine in 9% (6-12) of the patients with delirium. In the first 24 h in the ICU, all subtypes of delirium [hyperactive, adjusted odds ratio (aOR) 29.7 (12.9-74.5); mixed 10.0 (5.0-20.2); hypoactive 3.0 (1.2-6.7)] and circulatory support 2.7 (1.7-4.3) were associated with haloperidol use. At 72 h after ICU admission, circulatory support remained associated with subsequent use of haloperidol, aOR 2.6 (1.1-6.9). Haloperidol use within 0-24 h and within 0-72 h of ICU admission was not associated with 90-day mortality [aOR 1.2 (0.5-2.5); p = 0.66] and [aOR 1.9 (1.0-3.9); p = 0.07], respectively. CONCLUSIONS: In our study, haloperidol was the main pharmacological agent used for delirium in adult patients regardless of delirium subtype. Benzodiazepines, other anti-psychotics and dexmedetomidine were other frequently used agents. Haloperidol use was not statistically significantly associated with increased 90-day mortality.

Novel method for evaluation of eye movements in patients with narcolepsy.

BACKGROUND: Narcolepsy causes abnormalities in the control of wake-sleep, non-rapid-eye-movement (non-REM) sleep and REM sleep, which includes specific eye movements (EMs). In this study, we aim to evaluate EM characteristics in narcolepsy as compared to controls using an automated detector. METHODS: We developed a data-driven method to detect EMs during sleep based on two EOG signals recorded as part of a polysomnography (PSG). The method was optimized using the manually scored hypnograms from 36 control subjects. The detector was applied on a clinical sample with subjects suspected for central hypersomnias. Based on PSG, multiple sleep latency test and cerebrospinal fluid hypocretin-1 measures, they were divided into clinical controls (N = 20), narcolepsy type 2 (NT2, N = 19), and narcolepsy type 1 (NT1, N = 28). We investigated the distribution of EMs across sleep stages and cycles. RESULTS: NT1 patients had significantly less EMs during wake, N1, and N2 sleep and more EMs during REM sleep compared to clinical controls, and significantly less EMs during wake and N1 sleep compared to NT2 patients. Furthermore, NT1 patients showed less EMs during NREM sleep in the first sleep cycle and more EMs during NREM sleep in the second sleep cycle compared to clinical controls and NT2 patients. CONCLUSIONS: NT1 patients show an altered distribution of EMs across sleep stages and cycles compared to NT2 patients and clinical controls, suggesting that EMs are directly or indirectly controlled by the hypocretinergic system. A data-driven EM detector may contribute to the evaluation of narcolepsy and other disorders involving the control of EMs.

Parents' experience of a follow-up meeting after a child's death in the Paediatric Intensive Care Unit.

OBJECTIVE: 'To identify parents' experience of a follow up meeting and to explore whether the conversation was adequate to meet the needs of parents for a follow-up after their child's death in the Paediatric Intensive Care Unit (PICU). DESIGN AND SETTING: Qualitative method utilising semi-structured interviews with six pairs of parents 2-12 weeks after the follow-up conversation. The interviews were held in the parents' homes at their request. Data were analysed using a qualitative, descriptive approach and thematic analysis. FINDINGS: Four main themes emerged: (i) the way back to the PICU; (ii) framework; (iii) relations and (iv) closure. CONCLUSION: The parents expressed nervousness before the meeting, but were all pleased to have participated in these follow-up meetings. The parents found it meaningful that the follow-up meeting was interdisciplinary, since the parents could have answers to their questions both about treatment and care. It was important that the staff involved in the follow-up meeting were those who had been present through the hospitalisation and at the time of the child's death. Parents experienced the follow-up meeting as being a closure of the course in the PICU, regardless the length of the hospitalisation.

Implementation of the Danish return-to-work program: process evaluation of a trial in 21 Danish municipalities.

OBJECTIVES: The aim of this study was to evaluate the implementation of the Danish national return-to-work (RTW) program in 21 Danish municipalities. METHODS: We conducted a structured process evaluation on (i) reach and recruitment, (ii) fidelity, (iii) dose-delivered, (iv) dose-received, and (v) context by formulating 29 implementation criteria and analyzing qualitative and quantitative data from administrative records, interviews, field notes, and questionnaires. RESULTS: All municipalities integrated the basic features of the RTW program into the existing framework of the sickness benefit management system to an acceptable degree, ie, establishment of RTW teams, participation of RTW team members in the training courses, and following the general procedures of the program. However, the level of implementation varied considerably between the municipalities, particularly with respect to fidelity (defined as implementation consistent with the principles of the interdisciplinary RTW process). Five municipalities had high and eight had low fidelity scores. Similar large differences were found with regard to dose-delivered, particularly in the quality of cooperation with beneficiaries, employers, and general practitioners. Only 50% of the first consultations with the RTW coordinator were conducted in time. Among participants who were employed when their sickness absence period started, only 9% had at least one meeting with their workplace. CONCLUSION: It was feasible to implement the basic features of the Danish RTW program, however, large variations existed between municipalities. Establishment of well-functioning interdisciplinary RTW teams might require more time and resources, while ensuring early assessment and more frequent cooperation with employers might need more general adjustments in the Danish sickness benefit system.

Lower versus higher hemoglobin threshold for transfusion in septic shock.

BACKGROUND: Blood transfusions are frequently given to patients with septic shock. However, the benefits and harms of different hemoglobin thresholds for transfusion have not been established. METHODS: In this multicenter, parallel-group trial, we randomly assigned patients in the intensive care unit (ICU) who had septic shock and a hemoglobin concentration of 9 g per deciliter or less to receive 1 unit of leukoreduced red cells when the hemoglobin level was 7 g per deciliter or less (lower threshold) or when the level was 9 g per deciliter or less (higher threshold) during the ICU stay. The primary outcome measure was death by 90 days after randomization. RESULTS: We analyzed data from 998 of 1005 patients (99.3%) who underwent randomization. The two intervention groups had similar baseline characteristics. In the ICU, the lower-threshold group received a median of 1 unit of blood (interquartile range, 0 to 3) and the higher-threshold group received a median of 4 units (interquartile range, 2 to 7). At 90 days after randomization, 216 of 502 patients (43.0%) assigned to the lower-threshold group, as compared with 223 of 496 (45.0%) assigned to the higher-threshold group, had died (relative risk, 0.94; 95% confidence interval, 0.78 to 1.09; P=0.44). The results were similar in analyses adjusted for risk factors at baseline and in analyses of the per-protocol populations. The numbers of patients who had ischemic events, who had severe adverse reactions, and who required life support were similar in the two intervention groups. CONCLUSIONS: Among patients with septic shock, mortality at 90 days and rates of ischemic events and use of life support were similar among those assigned to blood transfusion at a higher hemoglobin threshold and those assigned to blood transfusion at a lower threshold; the latter group received fewer transfusions. (Funded by the Danish Strategic Research Council and others; TRISS ClinicalTrials.gov number, NCT01485315.).

Decreased sleep spindle density in patients with idiopathic REM sleep behavior disorder and patients with Parkinson's disease.

OBJECTIVE: To determine whether sleep spindles (SS) are potentially a biomarker for Parkinson's disease (PD). METHODS: Fifteen PD patients with REM sleep behavior disorder (PD+RBD), 15 PD patients without RBD (PD-RBD), 15 idiopathic RBD (iRBD) patients and 15 age-matched controls underwent polysomnography (PSG). SS were scored in an extract of data from control subjects. An automatic SS detector using a Matching Pursuit (MP) algorithm and a Support Vector Machine (SVM) was developed and applied to the PSG recordings. The SS densities in N1, N2, N3, all NREM combined and REM sleep were obtained and evaluated across the groups. RESULTS: The SS detector achieved a sensitivity of 84.7% and a specificity of 84.5%. At a significance level of α=1%, the iRBD and PD+RBD patients had a significantly lower SS density than the control group in N2, N3 and all NREM stages combined. At a significance level of α=5%, PD-RBD had a significantly lower SS density in N2 and all NREM stages combined. CONCLUSIONS: The lower SS density suggests involvement in pre-thalamic fibers involved in SS generation. SS density is a potential early PD biomarker. SIGNIFICANCE: It is likely that an automatic SS detector could be a supportive diagnostic tool in the evaluation of iRBD and PD patients.

Respiratory hazards of metal smelting.

PURPOSE OF REVIEW: The metal smelting industry is an important industry in the majority of countries in the world and employs millions of workers. In most of the production types, a variety of pollutants are emitted into the workplace atmosphere. Some of these pollutants have sensitizing properties, whereas other act as irritants in the respiratory tract. This review will explore the recent studies (2010-2012) which address the impact of exposure to pollutants in the smelting industry on nonmalignant respiratory disorders. RECENT FINDINGS: The association between different respiratory symptoms as well as pulmonary function and the level of exposure to different agents has been investigated. Likewise, the effect of primary prevention (exposure reduction) and secondary prevention (relocation) has been studied. Finally, the association between the incidence of community-acquired pneumonia and exposure to pollutants encountered at work in the smelting industry and the results from mortality studies are reported. SUMMARY: It appears that exposure to emissions of pollutants in the smelting industry is associated with respiratory symptoms, including asthma, lung function decline and chronic obstructive pulmonary disease, depending on the type of production. Moreover, it is possible that these exposures may enhance the risk of infectious pneumonia.

The Danish national return-to-work program--aims, content, and design of the process and effect evaluation.

The Danish national return-to-work (RTW) program aims to improve the management of municipal sickness benefit in Denmark. A study is currently ongoing to evaluate the RTW program. The purpose of this article is to describe the study protocol. The program includes 21 municipalities encompassing approximately 19 500 working-age adults on long-term sickness absence, regardless of reason for sickness absence or employment status. It consists of three core elements: (i) establishment of multidisciplinary RTW teams, (ii) introduction of standardized workability assessments and sickness absence management procedures, and (iii) a comprehensive training course for the RTW teams. The effect evaluation is based on a parallel group randomized trial and a stratified cluster controlled trial and focuses on register-based primary outcomes - duration of sickness absence and RTW - and questionnaire-based secondary outcomes such as health and workability. The process evaluation utilizes questionnaires, interviews, and municipal data. The effect evaluation tests whether participants in the intervention have a (i) shorter duration of full-time sickness absence, (ii) longer time until recurrent long-term sickness absence, (iii) faster full RTW, (iv) more positive development in health, workability, pain, and sleep; it also tests whether the program is cost-effective. The process evaluation investigates: (i) whether the expected target population is reached; (ii) if the program is implemented as intended; (iii) how the beneficiaries, the RTW teams, and the external stakeholders experience the program; and (iv) whether contextual factors influenced the implementation. The program has the potential to contribute markedly to lowering human and economic costs and increasing labor force supply. First results will be available in 2013. The trial registrations are ISRCTN43004323, and ISRCTN51445682.

Initial, successful implementation of sepsis guidelines in an emergency department.

INTRODUCTION: Early screening and treatment of sepsis can reduce mortality. Region Zealand established guidelines for the diagnosis and treatment of sepsis. We assess an interdisciplinary intervention for implementation of these guidelines at the Department of Emergency Medicine at Nykøbing Falster Hospital from July 2009 to August 2010. MATERIAL AND METHODS: Structured training was imparted to personnel during the first 18 weeks. Electronically accessible guidelines, posters with diagnostic and treatment algorithms, pocket references and checklists were made available to encourage adherence to the guidelines. Key nurses and doctors encouraged compliance. Journal audits (at baseline, 18 weeks and one year) were undertaken to measure adherence to six elements of the sepsis guidelines: lactate measurement, oxygen and fluid treatment, timely antibiotic treatment, blood culture and planning of treatment monitoring. RESULTS: A total of 27 (baseline), 29 (18 weeks) and 48 (one year) patients were included for analysis. Adherence to 3-5 of the elements of the sepsis guidelines' six elements increased from 37% to 65% from baseline to the first follow-up at 18 weeks (p = 0.03). Adherence to 3-5 of the elements decreased from the first to the second follow-up at one year. Lactate measurement, blood culture and antibiotic administration increased from baseline to the one-year follow-up. CONCLUSION: The intervention had a positive effect on the implementation of guidelines. This effect was reduced one year after the baseline audit, possibly due to a decline in the focus on the intervention and/or personnel turnover in the department.

Validation of a novel automatic sleep spindle detector with high performance during sleep in middle aged subjects.

Many of the automatic sleep spindle detectors currently used to analyze sleep EEG are either validated on young subjects or not validated thoroughly. The purpose of this study is to develop and validate a fast and reliable sleep spindle detector with high performance in middle aged subjects. An automatic sleep spindle detector using a bandpass filtering approach and a time varying threshold was developed. The validation was done on sleep epochs from EEG recordings with manually scored sleep spindles from 13 healthy subjects with a mean age of 57.9 ± 9.7 years. The sleep spindle detector reached a mean sensitivity of 84.6 % and a mean specificity of 95.3 %. The sleep spindle detector can be used to obtain measures of spindle count and density together with quantitative measures such as the mean spindle frequency, mean spindle amplitude, and mean spindle duration.

Can we always trust rhinomanometry?

OBJECTIVES: Rhinomanometry before and after decongestion distinguishes a nasal airway organic stenosis from congestion of nasal mucosa in patients with nasal stuffiness. Together with rhinoscopy and patient history, it is used to decide if nasal surgery would benefit the patient. Rhinomanometry measurements should thus be reliable and reproducible. MATERIALS AND METHODS: We performed repetitive active anterior rhinomanometry in 9 persons during 5 months to test reproducibility of nasal airway resistance (NAR) over time. We also did test-retest measurements in several participants. Xylometazoline hydrochloride was applied in each nasal cavity to minimize effects of mucosal variation and the nasal cavity was examined with rhinoscopy. The participants evaluated subjective nasal stuffiness on a visual analogue scale (VAS). RESULTS: The long term mean coefficient of variation (CV) of NAR over time was 27% for the whole group while the short term CV was 7 - 17% for test-retest within an hour. Mean NAR reduction after decongestion was 33%, but 13% of NAR values were not reduced after decongestion. Participants had difficulties estimating stuffiness on a VAS in 15% of the assessments, but there was no correlation between the VAS estimates and NAR. CONCLUSION: We found a high NAR variation over a period of five months. This implies low long-term rhinomanometry reproducibility and we suggest future research on standardised decongestion to increase the reproducibility.

Automatic sleep scoring in normals and in individuals with neurodegenerative disorders according to new international sleep scoring criteria.

The aim of this study was to develop a fully automatic sleep scoring algorithm on the basis of a reproduction of new international sleep scoring criteria from the American Academy of Sleep Medicine. A biomedical signal processing algorithm was developed, allowing for automatic sleep depth quantification of routine polysomnographic recordings through feature extraction, supervised probabilistic Bayesian classification, and heuristic rule-based smoothing. The performance of the algorithm was tested using 28 manually classified day-night polysomnograms from 18 normal subjects and 10 patients with Parkinson disease or multiple system atrophy. This led to quantification of automatic versus manual epoch-by-epoch agreement rates for both normals and abnormals. Resulting average agreement rates were 87.7% (Cohen's Kappa: 0.79) and 68.2% (Cohen's Kappa: 0.26) in the normal and abnormal group, respectively. Based on an observed reliability of the manual scorer of 92.5% (Cohen's Kappa: 0.87) in the normal group and 85.3% (Cohen's Kappa: 0.73) in the abnormal group, this study concluded that although the developed algorithm was capable of scoring normal sleep with an accuracy around the manual interscorer reliability, it failed in accurately scoring abnormal sleep as encountered for the Parkinson disease/multiple system atrophy patients.

Evaluation of aspirin response by Multiplate whole blood aggregometry and light transmission aggregometry.

Several studies indicate that a biochemically reduced response to aspirin increases the risk of cardiovascular events. This study was designed to investigate the performance of Multiplate whole blood aggregometry as regards assessment of platelet function prior to and after aspirin treatment, and to compare it with light transmission aggregometry (LTA). We included 21 healthy individuals and 43 patients with documented coronary artery disease (CAD). Platelet aggregation induced by arachidonic acid 0.5 mM was measured in duplicate by Multiplate aggregometry and LTA in healthy individuals before aspirin treatment and in all participants on four consecutive days during treatment with 75 mg aspirin daily. Optimal compliance was confirmed by complete suppression of serum thromboxane B(2) in all participants. Employing the Multiplate, the coefficient of variation (CV) was lower at baseline (CV = 8%) than during aspirin treatment in both healthy individuals (CV = 46%) and patients (CV = 46%). During aspirin treatment, the repeatability of LTA was superior to Multiplate measurements. However, the Multiplate was superior to LTA as regards the ability to discriminate platelet response before and after aspirin treatment. In conclusion, the repeatability of Multiplate aggregometry was good before aspirin treatment, whereas the CV was quite high during aspirin treatment in both healthy individuals and patients. However, the Multiplate device was fully capable of assessing platelet function prior to and after treatment with aspirin. Clinical studies are needed to investigate whether a high platelet aggregation level measured by Multiplate whole blood aggregometry during aspirin treatment is associated with a poor clinical outcome.

What happens to patients with nasal stuffiness and pathological rhinomanometry left without surgery?

In this study we explored long term outcomes of patients with nasal stuffiness and high nasal airway resistance (NAR) that did not undergo nasal surgery. The same investigation was repeated on average 8 years after a baseline investigation with an ENT-examination, a rhinomanometric survey and a rhinomanometry. We did follow-up investigations in 44 out of 59 non-operated patients with a pathological NAR on at least one side. At follow-up 2 persons (4%) had no complaints, 14 (32%) had reduced, 22 (50%) unchanged, and 6 (14%) increased complaints of nasal stuffiness. Rhinomanometry showed that NAR values decreased significantly between baseline and follow-up on both wider and narrower sides after decongestion. There was no correlation between subjective nasal complaints and NAR-values. In logistic regression models increasing age and allergy prevalence at baseline were significantly associated with having no, or reduced nasal stuffiness at follow-up. The results show that both NAR and subjective nasal stuffiness decreased with age. Consequently, we suggest that NAR normal values should be age adjusted. Also, a wait and see policy towards nasal stuffiness seems relevant since 36% of our patients had no or reduced nasal stuffiness while their NAR-values were reduced after 8 years.

T-cell receptor excision circles (TREC) in CD4+ and CD8+ T-cell subpopulations in atopic dermatitis and psoriasis show major differences in the emission of recent thymic emigrants.

We used T-cell receptor excision circles (TREC) to evaluate thymic function in adult patients with atopic dermatitis and psoriasis. We observed that men, but not women, with atopic dermatitis had a significantly faster decline in TREC content with increasing age compared with healthy men. In contrast, both men and women with psoriasis had significantly reduced TREC levels, which were, on average, only 30% of that of healthy persons. In atopic dermatitis the levels of TREC declined with increasing levels of IgE, disease intensity and extent of eczema. Furthermore, patients with atopic dermatitis showed signs of altered thymus function, as they had a significantly greater variation in TREC content measured over time than healthy controls, especially within the CD8+ T-cell subpopulation. Because both atopic dermatitis and psoriasis patients have an increased number of T-cells, this indicates that atopic dermatitis patients can have compensatory emissions of thymic emigrants, whereas psoriatic patients do not, thus supporting different thymic function in these two diseases.

Aspirin response evaluated by the VerifyNow Aspirin System and light transmission aggregometry.

INTRODUCTION: Patients with inadequate platelet inhibition by aspirin, referred to as aspirin resistance, might have an increased risk of suffering cardiovascular events. Therefore, identification of these patients by measuring platelet function is of great interest. Our objectives were to evaluate performance parameters of VerifyNow and to determine the agreement between VerifyNow and light transmission aggregometry (LTA) ad modum Born. MATERIALS AND METHODS: We included 21 healthy volunteers and 40 patients with stable coronary artery disease. Duplicate measurements of platelet aggregation were performed using VerifyNow and LTA (arachidonic acid 1.0 mM) in healthy volunteers before aspirin and in all participants on four consecutive days during treatment with non-enteric-coated aspirin 75 mg daily. VerifyNow test results were expressed in Aspirin Reaction Units (ARU) and LTA test results in percent of maximal aggregation. The cut-off for determination of aspirin resistance was > or =550 ARU and > or =20%, respectively. RESULTS: All participants were compliant, confirmed by complete suppression of serum-thromboxane B(2). VerifyNow was highly repeatable with a coefficient of variance of 0.5% at baseline and 3.0% during aspirin treatment. No individuals were identified as aspirin resistant with VerifyNow, whereas seven (12%) individuals were identified with LTA. ROC analysis using LTA as the gold standard showed poor sensitivity and good specificity with a cut-off at 550 ARU. CONCLUSION: VerifyNow was highly repeatable, but further studies are needed to investigate the relevance of the cut-off level at 550 ARU for detecting aspirin resistance.

Risk factors for invasive squamous cell carcinoma of the vulva and vagina--population-based case-control study in Denmark.

The etiology of vulvar and vaginal squamous cell carcinoma (VV-SCC) has received little attention. A total of 182 women with invasive VV-SCC (116 with VV-SCC(vulva), 66 with VV-SCC(vagina)), 164 uterine corpus cancer controls and 518 population controls were interviewed in a population-based case-control study in Denmark, and 87 (48%) of the VV-SCC cases had tissue samples examined for human papillomavirus (HPV) DNA using the GP5+/6+ PCR-EIA assay and subsequent reverse line blotting for HPV typing. Logistic regression-derived odds ratios with 95% confidence intervals served as relative risks. Cervical cancer-associated high-risk HPVs (hrHPVs) were detectable in most (89%) examined cases of VV-SCC(vagina) and in half (50%) of cases of VV-SCC(vulva) (p < 0.001). In site-specific multivariate logistic regression analyses, statistically significant risk factors for both VV-SCC(vulva) and VV-SCC(vagina) included measures of hrHPV exposure (anogenital warts for VV-SCC(vulva); cervical neoplasia and poor genital hygiene for VV-SCC(vagina)), tobacco smoking and alcohol consumption. Furthermore, socioeconomic variables (marital status and years at school) were associated with risk of VV-SCC(vulva). Comparing hrHPV-positive and hrHPV-negative VV-SCCs in polytomous logistic regression analysis revealed that tobacco smoking and cervical neoplasia were significant risk factors only for hrHPV-positive VV-SCCs. Our study shows that VV-SCC(vulva) and VV-SCC(vagina) share measures of prior hrHPV exposure, tobacco smoking and alcohol consumption as statistically significant risk factors. HPV vaccination programs aimed at reducing the burden of cervical cancers are likely to also provide considerable protection against VV-SCCs.

ProCNP and CNP are expressed primarily in male genital organs.

Lack of knowledge about the cellular origin of C-type natriuretic peptides (CNP) in the body has hampered the understanding of their biology. We examined the tissue specific expression of proCNP and CNP in the pig. The concentration of the CNP precursor, proCNP, was measured in extracts of 32 different tissues using a newly developed RIA. In 22 tissue extracts, we also measured CNP using a commercial RIA. In selected tissues, CNP mRNA was quantified by PCR, and the cellular CNP and proCNP localization was visualized by immunocytochemistry. Extracts from selected tissues were examined by gel chromatography. The highest peptide concentrations were found in extracts from the epididymis, seminal vesicles and prostate. CNP mRNA in the seminal vesicles and epididymis was 125-fold higher than in the other tissues examined. Gel chromatography showed that a CNP-53-like peptide is the dominant CNP tissue-form. Immunocytochemistry confirmed the pattern of peptide expression measured by RIA. In conclusion most proCNP-derived peptides are synthesized in epithelial cells in the epididymis, the prostate gland and in the seminal vesicles. The expression in male genital organs suggests a role of CNP in reproduction.

Metastasizing malignant pleomorphic adenoma in a young man.

We present the case of a younger man with metastasizing carcinoma of unknown primary site, where autopsy revealed a malignant pleomorphic adenoma (MPA) of the submandibular gland. MPA is very rare in young persons.