Middle aged wasps mate through most of the year, without regard to body size, ovarian development and nestmateship: a laboratory study of the primitively eusocial wasp Ropalidia marginata

We studied the mating behaviour of the primi-tively eusocial wasp Ropalidia marginata and the factors that may influence sperm transfer. By introducing a male and a female R. marginata into ventilated transparent plastic boxes, we were able to observe mating behaviour, and it involved mounting and short or long conjugation of the wasps. Dissection of female wasps after the observation indicated that long conjugation is a good behavioural predictor of sperm transfer. This finding makes it possible to obtain mated females without dissecting them every time. We tested the effect of age, season, relatedness, body size and female's ovarian status on mating. Under laboratory conditions, mating success declined rapidly below and above the ages 5-20 days. Within this age range mating success was significantly low in December compared to other months tested. There was no nestmate discrimination, and there was no influence of male and female body size or of the ovarian state of the female on the probability of sperm transfer.

Men´s health behaviour, health beliefs and need for health counselling : A study amongst 40-year-old males from one Helsinki City region

Tavoitteena oli tutkia 40-vuotiaiden miesten terveyskäyttäytymistä, terveysuskomuksia ja miesten saamaa terveysneuvontaa Helsingissä. 273 miestä vastasi kyselyyn ja osallistui terveystutkimuksiin. Terveydentilan perusteella miehet arvioitiin matalan (n=145) ja korkean (n=128) riskin ryhmiin. Khin neliö-testillä tutkittiin elämäntapa- ja riskitekijöitä koetun terveyden (hyvä, keskinkertainen/huono) luokissa ja verrattiin matalan ja korkean riskin ryhmiä em. tekijöiden osalta. Askeltavalla logistisella regressiomallilla analysoitiin tulosmuuttujia taustatekijöiden, terveyskäyttäytymisen, terveysuskomusten ja kliinisten riskitekijöiden avulla sekä arvioitiin oireiden ja vaivojen suhdetta koettuun terveydentilaan. Korkeassa riskissä olevien terveyttä seurattiin vuosina 2001–2004 analysoimalla mini-intervention vaikutusta terveysriskeihin ja elintapoihin varianssianalyysin avulla (ANOVA) (n=46). Matalasta vastausprosentista johtuen (39.6%), ei-vastanneiden aineistoa kerättiin käyttämällä syvähaastattelua (n=28) sekä puhelinkyselyä (n=40). Lopullinen aineisto koostui 341 miehestä. Tulokset osoittivat, että miehillä oli sydän- ja verisuonitautiriskejä. Kaksi kolmesta osallistuneista oli ylipainoisia tai lihavia, yli kolmanneksella vyötärönympärys oli ≥100 cm, ja yli 40%:llä oli diastolinen verenpaine ≥90 mmHg. Yli puolet tupakoi päivittäin ja 40% käytti alkoholia runsaasti. Ristiriitaisuutta ilmensi se, että huolimatta riskitekijöistä noin puolet miehistä koki terveydentilansa hyväksi. Sairauden tai vamman puute, hyvä suun terveydentila ja normaali vyötärönympärys olivat yhteydessä hyväksi koettuun terveydentilaan. Suora yhteys voitiin havaita omaisten tarjoaman neuvonnan ja vähäisen alkoholin käytön välillä. Masennus ja unettomuus olivat voimakkaasti yhteydessä loppuun palamiseen. Miehillä oli erilaisia fyysisiä ja psyykkisiä oireita, jotka korreloivat voimakkaasti masennuksen kanssa. Pieni määrä miehistä koki saaneensa terveysneuvontaa hoitohenkilökunnalta verrattuna perheenjäseniltä saatuun ohjaukseen. Korkeariskisten miesten (n=46) arvot parantuivat merkitsevästi lyhyellä aikavälillä. Kolesteroliarvoja lukuunottamatta ne palautuivat kolmen vuoden kuluttua alkumittausarvoja kohti. Laadullinen tutkimus osoitti, että “ei-vastanneet“ eivät osallistuneet projektiin, sillä he olivat oireettomia tai kiireisiä. Heillä todettiin samoja terveysriskejä kuin projektiin osallistuneilla. Syvähaastattelussa miehet toivat esille kokemuksiaan huolista, vihan tunteista, peloista ja yksinäisyydestä. Hoidonantajien on tärkeää ymmärtää ristiriidat miesten subjektiivisen ja objektiivisen terveydentilan välillä, mikä auttaa havaitsemaan esteitä terveyskäyttäytymiselle. Yhä enemmän tarvitaan yhteistyötä yksityisen ja julkisen terveydenhuollon välillä varmistamaan terveystottumusten jatkuminen miesten keskuudessa.

Impact of hysterectomy or levonorgestrel-releasing intrauterine system on ovarian function, bone, and sexual functioning in menorrhagic patients

The `VuoKKo` trial consisted of 236 women referred and randomised due to menorrhagia in the five university hospitals of Finland between November 1994 and November 1997. Of these women, 117 were randomised to hysterectomy and 119 to use levonorgestrel-releasing intrauterine system (LNG-IUS) to treat this complaint. Their follow-up visits took place six and twelve months after the treatment and five years after the randomisation. The first aim in the primary trial was quality-of-life and monetary aspects, and secondly in the present study to compare ovarian function, bone mineral density (BMD) and sexual functioning after these two treatment options. Ovarian function seemed to decrease after hysterectomy, demonstrated by increased hot flashes and serum follicle-stimulating hormone concentrations twelve months after the operation. Such an increase was not seen among LNG-IUS users. The pulsatility index of intraovarian arteries measured by two-dimensional ultrasound decreased in the hysterectomy group, but not in the LNG-IUS group. The decrease in serum inhibin B concentrations was similar in both groups, while ovarian artery circulation remained unchanged. BMD of the women measured by dual x-ray absorptiometry (DXA) at the lumbar spine and femoral neck at baseline and at five years after treatment showed BMD decrease at the lumbar spine among hysterectomised women, but not among LNG-IUS users. In both groups, BMD at the femoral neck had decreased. Differences between the groups were not, however, significant. Sexual functioning assessed by McCoy s sexual scale showed that sexual satisfaction as well as intercourse frequency had increased and sexual problems decreased among hysterectomised women six months after treatment. Among LNG-IUS users, sexual satisfaction and sexual problems remained unchanged. Although, the two groups did not differ in terms of sexual satisfaction or sexual problems at one-year and five-year follow-ups, LNG-IUS users were less satisfied with their partners than hysterectomised women.

Cutaneous porphyrias : Clinical and histopathological study

The prevalence of variegate porphyria (VP) (2.1:100 000, in 2006 n=108) was higher in Finland than elsewhere in European countries due to a founder effect (R152C). The incidence of VP was estimated at 0.2:1 000 000 based on the number of new symptomatic patients yearly. The prevalence of porphyria cutanea tarda (PCT) was 1.2:100 000 (in 2006 n=63), which is only one fourth of the numbers reported from other European countries. The estimated incidence of PCT was 0.5:1 000 000. Based on measurements of the uroporphyrinogen decarboxylase activity in erythrocytes, the proportion of familial PCT was 49% of the cases. The prevalence of erythropoietic protoporphyria (EPP) was at 0.8:100 000 (in 2006 n=39) including asymptomatic carriers of a mutation in the ferrochelatase (FECH) gene. The incidence of EPP was estimated at 0.1:1 000 000. After 1980 the penetrance was 37% among patients with VP. Of the mutation carriers (n=57) 30% manifested with skin symptoms. Frequency of skin symptom as only clinical sign was stable before or after 1980 (22% vs. 21%), but acute attacks became infrequent (29% vs. 7%). Of the symptomatic patients 30% had both acute attacks and skin symptoms and 80% had skin symptoms. Fragility (95%) and blistering (46%) of the skin in the backs of the hands were the most common skin symptoms. Transient correction of porphyrin metabolism using eight haem arginate infusions within five weeks had no effect on the skin symptoms in three of four patients with VP. In one case skin symptoms disappeared transiently. One patient with homozygous VP had severe photosensitivity since birth. Sensory polyneuropathy, glaucoma and renal failure developed during the 25-year follow-up without the presence of acute attacks. The I12T mutation was detected in both of his alleles in the protoporphyrinogen oxidase gene. Lack of skin symptoms and infrequency of acute attacks (1/9) in the patients with I12T mutation at the heterozygous stage indicate a mild phenotype (the penetrance 11%). Four mutations (751delGAGAA, 1122delT, C286T, C343T) in the FECH gene were characterised in four of 15 families with EPP. Burning pain (96%) and swelling (92%) of the sun-exposed skin were the major skin symptoms. Hepatopathy appeared in one of 25 symptomatic patients (4%). Clinical manifestations and associated factors of PCT were similar in the sporadic and familial types of PCT. The majority of the patients with PCT had one to three precipitating factors: alcohol intake (78%), mutations in hemochromatosis associated gene (50%), use of oestrogen (25% of women) and hepatitis B or C infections (25 %). Fatty liver disease (67%) and siderosis (67%) were commonly found in their liver biopsies. The major histopathological change of the sun-exposed skin in the patients with VP (n=20), EPP (n=8) and PCT (n=5) was thickening of the vessel walls of the upper dermis suggesting that the vessel wall is the primary site of the phototoxic reaction in each type of porphyria. The fine structure of the vessel walls was similar in VP, EPP and PCT consisting of the multilayered basement membrane and excess of finely granular substance between the layers which were surrounded by the band of homogenous material. EPP was characterised by amorphous perivascular deposits extending also to the extravascular space. In direct immunofluorescence study homogenous IgG deposits in the vessel walls of the upper dermis of the sun-exposed skin were demonstrated in each type of porphyria. In EPP the excess material around vessel walls consisted of other proteins such as serum amyloid protein, and kappa and lambda light chains in addition to the basement membrane constituents such as collagen IV and laminin. These results suggest that the alterations of the vessel walls are a consequence of the repeated damage and the repairing process in the vessel wall. The microscopic alterations could be demonstrated even in the normal looking but sun-exposed skin of the patients with EPP during the symptom-free phase suggesting that vascular change can be chronic. The stability of vascular changes in the patients with PCT after treatment indicates that circulating porphyrins are not important for the maintenance of the changes.

Hospital-related fears and coping strategies in 4-6-year-old children

There is only little information available on the 4-6-year-old child s hospital-related fears, and on the coping with such fears, as expressed by the children themselves. However, previous data collected from parents and hospital personnel indicate that hospitalization is an anxiety-producing experience for young children. The purpose of this study was to describe the experience of hospital-related fears and the experience of coping with hospital-related fears of 4-6-year-old children. The aim of this study was to form a descriptive model of the subjective experience of hospital-related fears and coping strategies of 4-6-year old children. The data were collected by interviewing 4-6-year-old children from a hospital and kindergarten settings in Finland from 2004 to 2006. Ninety children were interviewed in order to describe the hospital-related fear and the experience of fear, and 89 to describe their coping with the fear and the experience of coping. The children were chosen through purposive sampling. The data were gathered by semi-structured interview, supported by pictures. The data about hospital-related fears and on strategies for coping with hospital-related fears were reviewed by qualitative and quantitative methods. The experience of hospital-related fears and coping with these fears were analyzed using Colaizzi s Method of Phenomenological Analysis. The results revealed that more than 90 % of the children said they were afraid of at least one thing in hospital. Most of the fears could be categorized as nursing interventions, fears of being a patient, and fears caused by the developmental stage of the child. Children interviewed in the hospital expressed substantially more fears than children interviewed in kindergarten. Children s meanings of hospital-related fears were placed into four main clusters: 1) insecurity, 2) injury, 3) helplessness, 4) and rejection. The results also showed that children have plenty of coping strategies, to deal with their fears, especially such strategies in which the children themselves play an active role. Most often mentioned coping strategies were 1) the presence of parents and other family members, 2) the help of the personnel, 3) positive images and humour, 4) play, and 5) the child s own safety toy. The children interviewed in the hospital mentioned statistically significantly more often play, positive imagination and humour as their coping strategy than children interviewed in kindergarten. The meaning of coping with hospital fears consisted of six clusters: pleasure, security, care, understanding the meaning of the situation participating, and protecting oneself. Being admitted to a hospital is an event which may increase the fears of a 4-6-year-old child. Children who have personal experience of being admitted to a hospital describe more fears than healthy children in kindergarten. For young children, hospital-related fear can be such a distressing experience that it reflects on their feelings of security and their behaviour. Children can sometimes find it difficult to admit their fear. Children need the help of adults to express their hospital-related fears, the objects of the fears, and to cope with the fears. Personnel should be aware of children s fears and support them in the use of coping strategies. In addition to the experiences of security and care, pre-school-aged children need active coping strategies that they can use themselves, regardless of the presence of the parents or nurses. Most of all, children need the possibility to play and experience pleasure. Children can also be taught coping strategies which give them an active, positive role.

Preterm Birth and Surgical Treatment of the Uterine Cervix

Cervical cancer is the second most common cancer among women globally. Most, probably all cases, arise through a precursor, cervical intraepithelial neoplasia (CIN). Effective cytological screening programmes and surgical treatments of precancerous lesions have dramatically reduced its prevalence and related mortality. Although these treatments are effective, they may have adverse effects on future fertility and pregnancy outcomes. The aim of this study was to evaluate the effects of surgical treatment of the uterine cervix on pregnancy and fertility outcomes, with the focus particularly on preterm birth. The general preterm birth rates and risk factors during 1987–2005 were studied. Long-term mortality rates of the treated women were studied. In this study, information from The Medical Birth Register (MBR), The Hospital Discharge Register (HDR), The Cause-of-Death Register (CDR), and hospital records were used. Treatments were performed during 1987–2003 and subsequent deliveries, IVF treatments and deaths were analyzed. The general preterm birth rate in Finland was relatively stable, varying from 5.1% to 5.4% during the study period (1987 to 2005), although the proportion of extremely preterm births had decreased substantially by 12%.The main risk factor as regards preterm birth was multiplicity, followed by elective delivery (induction of delivery or elective cesarean section), primiparity, in vitro fertilization treatment, maternal smoking and advanced maternal age. The risk of preterm birth and low birth weight was increased after any cervical surgical treatment; after conization the risk of preterm birth was almost two-fold (RR 1.99, 95% CI 1.81– 2.20). In the conization group the risk was the highest for very preterm birth (28–31 gestational weeks) and it was also high for extremely preterm birth (less than 28 weeks). In this group the perinatal mortality was also increased. In subgroup analysis, laser ablation was not associated with preterm birth. When comparing deliveries before and after Loop conization, we found that the risk of preterm birth was increased 1.94-fold (95% CI 1.10–3.40). Adjusting for age, parity, or both did not affect our results. Large or repeat cones increased the risk of preterm birth when compared with smaller cones, suggesting that the size of the removed cone plays a role. This was corroborated by the finding that repeat treatment increased the risk as much as five-fold when compared with the background preterm birth rate. We found that the proportion of IVF deliveries (1.6% vs. 1.5%) was not increased after treatment for CIN when adjusted for year of delivery, maternal age, or parity. Those women who received both treatment for CIN and IVF treatment were older and more often primiparous, which explained the increased risk of preterm birth. We also found that mortality rates were 17% higher among women previously treated for CIN. This excess mortality was particularly seen as regards increased general disease mortality and alcohol poisoning (by 13%), suicide (by 67%) and injury death (by 31%). The risk of cervical cancer was high, as expected (SMR 7.69, 95% CI 4.23–11.15). Women treated for CIN and having a subsequent delivery had decreased general mortality rate (by -22%), and decreased disease mortality (by -37%). However, those with preterm birth had increased general mortality (SMR 2.51, 95% CI 1.24–3.78), as a result of cardiovascular diseases, alcohol-related causes, and injuries. In conclusion, the general preterm birth rate has not increased in Finland, as in many other developed countries. The rate of extremely preterm births has even decreased. While other risk factors of preterm birth, such as multiplicity and smoking during pregnancy have decreased, surgical treatments of the uterine cervix have become more important risk factors as regards preterm birth. Cervical conization is a predisposing factor as regards preterm birth, low birth weight and even perinatal mortality. The most frequently used treatment modality, Loop conization, is also associated with the increased risk of preterm birth. Treatments should be tailored individually; low-grade lesions should not be treated at all among young women. The first treatment should be curative, because repeat treatments are especially harmful. The proportion of IVF deliveries was not increased after treatment for CIN, suggesting that current treatment modalities do not strongly impair fertility. The long-term risk of cervical cancer remains high even after many years post-treatment; therefore careful surveillance is necessary. In addition, accidental deaths and deaths from injury were common among treated women, suggesting risk-taking behavior of these women. Preterm birth seems be associated with extremely high mortality rates, due to cardiovascular, alcohol-related and injury deaths. These women could benefit from health counseling, for example encouragement in quitting smoking.

The application of learning analytics to improve learning: Questions from the academy

Since 2007, close collaboration between the Learning and Teaching Unit’s Academic Quality and Standards team and the Department of Reporting and Analysis’ Business Objects team resulted in a generational approach to reporting where QUT established a place of trust. This place of trust is where data owners are confident in date storage, data integrity, reported and shared. While the role of the Department of Reporting and Analysis focused on the data warehouse, data security and publication of reports, the Academic Quality and Standards team focused on the application of learning analytics to solve academic research questions and improve student learning. Addressing questions such as: • Are all students who leave course ABC academically challenged? • Do the students who leave course XYZ stay within the faculty, university or leave? • When students withdraw from a unit do they stay enrolled on full or part load or leave? • If students enter through a particular pathway, what is their experience in comparison to other pathways? • With five years historic reporting, can a two-year predictive forecast provide any insight? In answering these questions, the Academic Quality and Standards team then developed prototype data visualisation through curriculum conversations with academic staff. Where these enquiries were applicable more broadly this information would be brought into the standardised reporting for the benefit of the whole institution. At QUT an annual report to the executive committees allows all stakeholders to record the performance and outcomes of all courses in a snapshot in time or use this live report at any point during the year. This approach to learning analytics was awarded the Awarded 2014 ATEM/Campus Review Best Practice Awards in Tertiary Education Management for The Unipromo Award for Excellence in Information Technology Management.

Promotion of a cancer-like phenotype, through chronic exposure to inflammatory cytokines and hypoxia in a bronchial epithelial cell line model

Globally, lung cancer accounts for approximately 20% of all cancer related deaths. Five-year survival is poor and rates have remained unchanged for the past four decades. There is an urgent need to identify markers of lung carcinogenesis and new targets for therapy. Given the recent successes of immune modulators in cancer therapy and the improved understanding of immune evasion by tumours, we sought to determine the carcinogenic impact of chronic TNF-α and IL-1β exposure in a normal bronchial epithelial cell line model. Following three months of culture in a chronic inflammatory environment under conditions of normoxia and hypoxia (0.5% oxygen), normal cells developed a number of key genotypic and phenotypic alterations. Important cellular features such as the proliferative, adhesive and invasive capacity of the normal cells were significantly amplified. In addition, gene expression profiles were altered in pathways associated with apoptosis, angiogenesis and invasion. The data generated in this study provides support that TNF-α, IL-1β and hypoxia promotes a neoplastic phenotype in normal bronchial epithelial cells. In turn these mediators may be of benefit for biomarker and/or immune-therapy target studies. This project provides an important inflammatory in vitro model for further immuno-oncology studies in the lung cancer setting.

Early life determinants of atopy : A 20-year prospective follow-up study on unselected, healthy newborns

Atopy-related allergic diseases, i.e. allergic rhinoconjunctivitis, atopic dermatitis and asthma, have increased in frequency in the industrialized countries. In order to reverse this trend, effective preventive strategies need to be developed. This requires a better understanding of the early-life events leading to the expression of the atopic phenotype. The present study has aimed at defining early-life factors and markers associated with the subsequent development of allergic diseases in a cohort of 200 healthy, unselected Finnish newborns prospectively followed up from birth to age 20 years. Their mothers were encouraged to start and maintain exclusive breastfeeding as long as it was nutritionally sufficient for the infant. Consequently, all the infants received some duration of exclusive breastfeeding, 58% of the infants were on exclusive breastfeeding for the first 6 months of life, and 18% received this feeding at least for the first 9 months. Of the infants, 42% had a family history of allergy. After the first year of follow-up, the children were re-assessed at ages 5, 11 and 20 years with clinical examination, skin prick testing, and parental and personal interviews. Exclusive breastfeeding for over 9 months was associated with atopic dermatitis and symptoms of food hypersensitivity at age 5 years, and with symptoms of food hypersensitivity at age 11 years in the children with a familial allergy. Subjects with allergic symptoms or a positive skin prick test in childhood or adolescence had lower retinol concentrations during their infancy and childhood than others. An elevated cord serum immunoglobulin E concentration predicted subsequent atopic manifestations though with modest sensitivity. Children and adolescents with allergic symptoms, skin prick test positivity and an elevated IgE had lower total cholesterol levels in infancy and childhood than the nonatopic subjects. In conclusion, prolonging strictly exclusive breastfeeding for over 9 months of age was not of help in prevention of allergic symptoms; instead, it was associated with increased atopic dermatitis and food hypersensitivity symptoms in childhood. Due to the modest sensitivity, cord serum IgE is not an effective screening method for atopic predisposition in the general population. Retinol and cholesterol concentrations in infancy were inversely associated with the subsequent development of allergic symptoms. Based on these findings, it is proposed that there may be differences in the inborn regulation of retinol and cholesterol levels in children with and without a genetic susceptibility to atopy, and these may play a role in the development of atopic sensitization and allergic diseases.

Maallikon suorittama defibrillaatio sydänpysähdyspotilaan hoitoketjussa

Sudden cardiac arrest (CA) is one of the leading causes of death in Europe. It has been estimated that about 40 % of CA victims have ventricular fibrillation (VF) at the time of the first heart rhythm analysis. The treatment for VF is immediate cardiopulmonary resuscitation (CPR) and rapid defibrillation. The automated external defibrillator (AED) and the concept of public access defibrillation (PAD) may be a key to shortening defibrillation delays. Recent studies have shown that PAD programs are associated with high survival rates from VF when devices have been placed in certain risk sites and used by trained laypersons. Today many public places are equipped with AEDs. The purpose of this study was to find new ways of utilizing layperson defibrillation and promote the concept of public access defibrillation (PAD). The study explored the use of AEDs by non-medical first responders in Finland and cabin crew on board a commercial aircraft. A simulated study was performed to explore the role of dispatcher assistance in layperson CPR and defibrillation. A 15-year follow-up study of 59 one-year survivors after successful out-of-hospital resuscitation was performed to evaluate the long-term quality of life of the CA patients. Although there are many AEDs in use by non-medical first responders in Finland, the results of the study showed that there are large variations between individual first response units. This is considered to be caused by the lack of national standards and regulations that would define a full integration of first-responder programmes into the Emergency Medical Services system. The goal of rapid defibrillation in five minutes after the onset of CA is difficult to achieve in Finland due to sparse population and long distances. Local PAD programs may shorten the defibrillation delays. Dispatcher assistance in defibrillation by a layperson not trained to use an AED seems feasible and does not compromise the performance of CPR. In a simulated study, the quality of mouth-to-mouth ventilation performed by laypersons was found to be better after CPR training compared with performance with dispatcher assistance before training. Training was not found to have an influence on the quality of compressions or defibrillation compared with dispatcher assistance of untrained laypersons. The target groups for CPR and defibrillation training need further evaluation. The placements of the AEDs in public areas should be known by the emergency response center and the location should be marked with an international sign. The finding that once a good neurological outcome after CA is achieved, it can be maintained for more than 10 years, encourages further efforts to improve the survival of CA patients.

The importance of context in engaging students large first year management classes: A case study

Engaging large first year classes in tertiary education poses a number of significant challenges, most of which have been discussed by others. One area that has not received the kind of attention that it warrants is the context within which the engagement activities take place. This paper examines both the processes used to engage a large first year management class in a major city university and how the context of the classes shaped activities and student responses to these activities. It was recognised that students had certain types of learning styles, but given the total number of students (in excess of 1200) it was realised that is would be impossible to cater to all possibilities. A key outcome of the exercise was the importance of context in shaping student behaviours.

Thrombophilia and direct thrombin inhibitor lepirudin clinical and monitoring aspects

Thrombophilia (TF) predisposes both to venous and arterial thrombosis at a young age. TF may also impact the thrombosis or stenosis of hemodialysis (HD) vascular access in patients with end-stage renal disease (ESRD). When involved in severe thrombosis TF may associate with inappropriate response to anticoagulation. Lepirudin, a potent direct thrombin inhibitor (DTI), indicated for heparin-induced thrombocytopenia-related thrombosis, could offer a treatment alternative in TF. Monitoring of narrow-ranged lepirudin demands new insights also in laboratory. The above issues constitute the targets in this thesis. We evaluated the prevalence of TF in patients with ESRD and its impact upon thrombosis- or stenosis-free survival of the vascular access. Altogether 237 ESRD patients were prospectively screened for TF and thrombogenic risk factors prior to HD access surgery in 2002-2004 (mean follow-up of 3.6 years). TF was evident in 43 (18%) of the ESRD patients, more often in males (23 vs. 9%, p=0.009). Known gene mutations of FV Leiden and FII G20210A occurred in 4%. Vascular access sufficiently matured in 226 (95%). The 1-year thrombosis- and stenosis-free access survival was 72%. Female gender (hazards ratio, HR, 2.5; 95% CI 1.6-3.9) and TF (HR 1.9, 95% CI 1.1-3.3) were independent risk factors for the shortened thrombosis- and stenosis-free survival. Additionally, TF or thrombogenic background was found in relatively young patients having severe thrombosis either in hepatic veins (Budd-Chiari syndrome, BCS, one patient) or inoperable critical limb ischemia (CLI, six patients). Lepirudin was evaluated in an off-label setting in the severe thrombosis after inefficacious traditional anticoagulation without other treatment options except severe invasive procedures, such as lower extremity amputation. Lepirudin treatments were repeatedly monitored clinically and with laboratory assessments (e.g. activated partial thromboplastin time, APTT). Our preliminary studies with lepirudin in thrombotic calamities appeared safe, and no bleeds occurred. An effective DTI lepirudin calmed thrombosis as all patients gradually recovered. Only one limb amputation was performed 3 years later during the follow-up (mean 4 years). Furthermore, we aimed to overcome the limitations of APTT and confounding effects of warfarin (INR of 1.5-3.9) and lupus anticoagulant (LA). Lepirudin responses were assessed in vitro by five specific laboratory methods. Ecarin chromogenic assay (ECA) or anti-Factor IIa (anti-FIIa) correlated precisely (r=0.99) with each other and with spiked lepirudin in all plasma pools: normal, warfarin, and LA-containing plasma. In contrast, in the presence of warfarin and LA both APTT and prothrombinase-induced clotting time (PiCT®) were limited by non-linear and imprecise dose responses. As a global coagulation test APTT is useful in parallel to the precise chromogenic methods ECA or Anti-FIIa in challenging clinical situations. Lepirudin treatment requires multidisciplinary approach to ensure appropriate patient selection, interpretation of laboratory monitoring, and treatment safety. TF seemed to be associated with complicated thrombotic events, in venous (BCS), arterial (CLI), and vascular access systems. TF screening should be aimed to patients with repeated access complications or prior unprovoked thromboembolic events. Lepirudin inhibits free and clot-bound thrombin which heparin fails to inhibit. Lepirudin seems to offer a potent and safe option for treatment of severe thrombosis. Multi-centered randomized trials are necessary to assess the possible management of complicated thrombotic events with DTIs like lepirudin and seek prevention options against access complications.

Peripheral facial palsy : Grading, Etiology, and Melkersson-Rosenthal Syndrome

The objective of this study was to assess the utility of two subjective facial grading systems, to evaluate the etiologic role of human herpesviruses in peripheral facial palsy (FP), and to explore characteristics of Melkersson-Rosenthal syndrome (MRS). Intrarater repeatability and interrater agreement were assessed for Sunnybrook (SFGS) and House-Brackmann facial grading systems (H-B FGS). Eight video-recorded FP patients were graded in two sittings by 26 doctors. Repeatability for SFGS was from good to excellent and agreement between doctors from moderate to excellent by intraclass correlation coefficient and coefficient of repeatability. For H-B FGS, repeatability was from fair to good and agreement from poor to fair by agreement percentage and kappa coefficients. Because SFGS was at least as good in repeatability as H-B FGS and showed more reliable results in agreement between doctors, we encourage the use of SFGS over H-B FGS. Etiologic role of human herpesviruses in peripheral FP was studied by searching DNA of herpes simplex virus (HSV) -1 and -2, varicella-zoster virus (VZV), human herpesvirus (HHV) -6A, -6B, and -7, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) by PCR/microarray methods in cerebrospinal fluid (CSF) of 33 peripheral FP patients and 36 controls. Three patients and five controls had HHV-6 or -7 DNA in CSF. No DNA of HSV-1 or -2, VZV, EBV, or CMV was found. Detecting HHV-7 and dual HHV-6A and -6B DNA in CSF of FP patients is intriguing, but does not allow etiologic conclusions as such. These DNA findings in association with FP and the other diseases that they accompanied require further exploration. MRS is classically defined as a triad of recurrent labial or oro-facial edema, recurrent peripheral FP, and plicated tongue. All three signs are present in the minority of patients. Edema-dominated forms are more common in the literature, while MRS with FP has received little attention. The etiology and true incidence of MRS are unknown. Characteristics of MRS were evaluated at the Departments of Otorhinolaryngology and Dermatology focusing on patients with FP. There were 35 MRS patients, 20 with FP and they were mailed a questionnaire (17 answered) and were clinically examined (14 patients). At the Department of Otorhinolaryngology, every MRS patient had FP and half had the triad form of MRS. Two patients, whose tissue biopsies were taken during an acute edema episode, revealed nonnecrotizing granulomatous findings typical for MRS, the other without persisting edema and with symptoms for less than a year. A peripheral blood DNA was searched for gene mutations leading to UNC-93B protein deficiency predisposing to HSV-1 infections; no gene mutations were found. Edema in most MRS FP patients did not dominate the clinical picture, and no progression of the disease was observed, contrary to existing knowledge. At the Department of Dermatology, two patients had triad MRS and 15 had monosymptomatic granulomatous cheilitis with frequent or persistent edema and typical MRS tissue histology. The clinical picture of MRS varied according to the department where the patient was treated. More studies from otorhinolaryngology departments and on patients with FP would clarify the actual incidence and clinical picture of the syndrome.