Management of semi-natural grasslands for butterfly and moth communities

This work focuses on the factors affecting species richness, abundance and species composition of butterflies and moths in Finnish semi-natural grasslands, with a special interest in the effects of grazing management. In addition, an aim was set at evaluating the effectiveness of the support for livestock grazing in semi-natural grasslands, which is included in the Finnish agri-environment scheme. In the first field study, butterfly and moth communities in resumed semi-natural pastures were com-pared to old, annually grazed and abandoned previous pastures. Butterfly and moth species compo-sition in restored pastures resembled the compositions observed in old pastures after circa five years of resumed cattle grazing, but diversity of butterflies and moths in resumed pastures remained at a lower level compared with old pastures. None of the butterfly and moth species typical of old pas-tures had become more abundant in restored pastures compared with abandoned pastures. There-fore, it appears that restoration of butterfly and moth communities inhabiting semi-natural grass-lands requires a longer time that was available for monitoring in this study. In the second study, it was shown that local habitat quality has the largest impact on the occurrence and abundance of butterflies and moths compared to the effects of grassland patch area and connec-tivity of the regional grassland network. This emphasizes the importance of current and historical management of semi-natural grasslands on butterfly and moth communities. A positive effect of habitat connectivity was observed on total abundance of the declining butterflies and moths, sug-gesting that these species have strongest populations in well-connected habitat networks. Highest species richness and peak abundance of most individual species of butterflies and moths were generally observed in taller grassland vegetation compared with vascular plants, suggesting a preference towards less intensive management in insects. These differences between plants and their insect herbivores may be understood in the light of both (1) the higher structural diversity of tall vegetation and (2) weaker tolerance of disturbances by herbivorous insects due to their higher trophic level compared to plants. The ecological requirements of all species and species groups inhabiting semi-natural grasslands are probably never met at single restricted sites. Therefore, regional implementation of management to create differently managed areas is imperative for the conservation of different species and species groups dependent on semi-natural grasslands. With limited resources it might be reasonable to focus much of the management efforts in the densest networks of suitable habitat to minimise the risk of extinction of the declining species.

Phylogenetics, taxon delimitation and phylogenetic diversity

Throughout the history of Linnean taxonomy, species have been described with varying degrees of justification. Many descriptions have been based on only a few ambiguous morphological characters. Moreover, species have been considered natural, well-defined units whereas higher taxa have been treated as disparate, non-existent creations. In the present thesis a few such cases were studied in detail. Often the species-level descriptions were based on only a few specimens and the variation previously thought to be interspecific was found to be intraspecific. In some cases morphological characters were sufficient to resolve the evolutionary relationships between the taxa, but generally more resolution was gained by the addition of molecular evidence. However, both morphological and molecular data were found to be deceptive in some cases. The DNA sequences of morphologically similar specimens were found to differ distinctly in some cases, whereas in other closely related species the morphology of specimens with identical DNA sequences differed substantially. This study counsels caution when evolutionary relationships are being studied utilizing only one source of evidence or a very limited number of characters (e.g. barcoding). Moreover, it emphasizes the importance of high quality data as well as the utilization of proper methods when making scientific inferences. Properly conducted analyses produce robust results that can be utilized in numerous interesting ways. The present thesis considered two such extensions of systematics. A novel hypothesis on the origin of bioluminescence in Elateriformia beetles is presented, tying it to the development of the clicking mechanism in the ancestors of these animals. An entirely different type of extension of systematics is the proposed high value of the white sand forests in maintaining the diversity of beetles in the Peruvian Amazon. White sand forests are under growing pressure from human activities that lead to deforestation. They were found to harbor an extremely diverse beetle fauna and many taxa were specialists living only in this unique habitat. In comparison to the predominant clay soil forests, considerably more elateroid beetles belonging to all studied taxonomic levels (species, genus, tribus, and subfamily) were collected in white sand forests. This evolutionary diversity is hypothesized to be due to a combination of factors: (1) the forest structure, which favors the fungus-plant interactions important for the elateroid beetles, (2) the old age of the forest type favoring survival of many evolutionary lineages and (3) the widespread distribution and fragmentation of the forests in the Miocene, favoring speciation.

Place quality and urban competitiveness symbiosis? A position paper

Urban agglomerations—where innovation and knowledge generation activities take place—are in a tough competition to become a major player in the global knowledge economy. It is claimed that soft measures—namely quality of life and place—help in fostering and attracting talent, and consequently draw investment to these urban localities. This paper aims to scrutinise the role of soft measures in supporting urban competitiveness through a critical review of the scholarly literature. The findings shed some light on whether there is a symbiotic relationship between place quality and urban competitiveness. The paper also points out directions for future investigations.

Microneurovascular free muscle transfer with cross-over nerve grafts in facial reanimation

Microneurovascular free muscle transfer with cross-over nerve grafts in facial reanimation Loss of facial symmetry and mimetic function as seen in facial paralysis has an enormous impact on the psychosocial conditions of the patients. Patients with severe long-term facial paralysis are often reanimated with a two-stage procedure combining cross-facial nerve grafting, and 6 to 8 months later with microneurovascular (MNV) muscle transfer. In this thesis, we recorded the long-term results of MNV surgery in facial paralysis and observed the possible contributing factors to final functional and aesthetic outcome after this procedure. Twenty-seven out of forty patients operated on were interviewed, and the functional outcome was graded. Magnetic resonance imaging (MRI) of MNV muscle flaps was done, and nerve graft samples (n=37) were obtained in second stage of the operation and muscle biopsies (n=18) were taken during secondary operations.. The structure of MNV muscles and nerve grafts was evaluated using histological and immunohistochemical methods ( Ki-67, anti-myosin fast, S-100, NF-200, CD-31, p75NGFR, VEGF, Flt-1, Flk-1). Statistical analysis was performed. In our studies, we found that almost two-thirds of the patients achieved good result in facial reanimation. The longer the follow-up time after muscle transfer the weaker was the muscle function. A majority of the patients (78%) defined their quality of life improved after surgery. In MRI study, the free MNV flaps were significantly smaller than originally. A correlation was found between good functional outcome and normal muscle structure in MRI. In muscle biopsies, the mean muscle fiber diameter was diminished to 40% compared to control values. Proliferative activity of satellite cells was seen in 60% of the samples and it tended to decline with an increase of follow-up time. All samples showed intramuscular innervation. Severe muscle atrophy correlated with prolonged intraoperative ischaemia. The good long-term functional outcome correlated with dominance of fast fibers in muscle grafts. In nerve grafts, the mean number of viable axons amounted to 38% of that in control samples. The grafted nerves characterized by fibrosis and regenerated axons were thinner than in control samples although they were well vascularized. A longer time between cross facial nerve grafting and biopsy sampling correlated with a higher number of viable axons. P75Nerve Growth Factor Receptor (p75NGFR) was expressed in every nerve graft sample. The expression of p75NGFR was lower in older than in younger patients. A high expression of p75NGFR was often seen with better function of the transplanted muscle. In grafted nerve Vascular Endothelial Growth Factor (VEGF) and its receptors were expressed in nervous tissue. In conclusion, most of the patients achieved good result in facial reanimation and were satisfied with the functional outcome. The mimic function was poorer in patients with longer follow-up time. MRI can be used to evaluate the structure of the microneurovascular muscle flaps. Regeneration of the muscle flaps was still going on many years after the transplantation and reinnervation was seen in all muscle samples. Grafted nerves were characterized by fibrosis and fewer, thinner axons compared to control nerves although they were well vascularized. P75NGFR and VEGF were expressed in human nerve grafts with higher intensity than in control nerves which is described for the first time.

Laboratory analyses for evaluation of platelet disorders and platelet concentrates

High quality of platelet analytics requires specialized knowledge and skills. It was applied to analyze platelet activation and aggregation responses in a prospective controlled study of patients with Finnish type of amyloidosis. The 20 patients with AGel amyloidosis displayed a delayed and more profound platelet shape change than healthy siblings and healthy volunteers, which may be related to altered fragmentation of mutated gelsolin during platelet activation. Alterations in platelet shape change have not been reported in association with platelet disorders. In the rare Bernard-Soulier syndrome with Asn45Ser mutation of glycoprotein (GP) IX, the diagnostic defect in the expression of GPIb-IX-V complex was characterized in seven Finnish patients, also an internationally exceptionally large patient series. When measuring thrombopoietin in serial samples of amniotic fluid and cord blood of 15 pregnant women with confirmed or suspected fetal alloimmune thrombocytopenia, the lower limit of detection could be extended. The results approved that thrombopoietin is present already in amniotic fluid. The application of various non-invasive means for diagnosing thrombocytopenia (TP) revealed that techniques for estimating the proportion of young, i.e. large platelets, such as direct measurement of reticulated platelets and the mean platelet size, would be useful for evaluating platelet kinetics in a given patient. Due to different kinetics between thrombopoietin and increase of young platelets in circulation, these measurements may have most predictive value when measured from simultaneous samples. Platelet autoantibodies were present not only in isolated autoimmune TP but also in patients without TP where disappearance of platelets might be compensated by increased production. The autoantibodies may also persist after TP has been cured. Simultaneous demonstration of increased young platelets (or increased mean platelet volume) in peripheral blood and the presence of platelet associated IgG specificities to major glycoproteins (GPIb-IX and GPIIb-IIIa) may be considered diagnostic for autoimmune TP. Measurement of a soluble marker as a sign of thrombin activation and proceeding deterioration of platelet components was applied to analyze the alterations under several stress factors (storage, transportation and lack of continuous shaking under controlled conditions) of platelet products. The GPV measured as a soluble factor in platelet storage medium showed good correlation with an array of other measurements commonly applied in characterization of stored platelets. The benefits of measuring soluble analyte in a quantitative assay were evident.

Long-term clinical outcome after liver transplantation

With transplant rejection rendered a minor concern and survival rates after liver transplantation (LT) steadily improving, long-term complications are attracting more attention. Current immunosuppressive therapies, together with other factors, are accompanied by considerable long-term toxicity, which clinically manifests as renal dysfunction, high risk for cardiovascular disease, and cancer. This thesis investigates the incidence, causes, and risk factors for such renal dysfunction, cardiovascular risk, and cancer after LT. Long-term effects of LT are further addressed by surveying the quality of life and employment status of LT recipients. The consecutive patients included had undergone LT at Helsinki University Hospital from 1982 onwards. Data regarding renal function – creatinine and estimated glomerular filtration rate (GFR) – were recorded before and repeatedly after LT in 396 patients. The presence of hypertension, dyslipidemia, diabetes, impaired fasting glucose, and overweight/obesity before and 5 years after LT was determined among 77 patients transplanted for acute liver failure. The entire cohort of LT patients (540 patients), including both children and adults, was linked with the Finnish Cancer Registry, and numbers of cancers observed were compared to site-specific expected numbers based on national cancer incidence rates stratified by age, gender, and calendar time. Health-related quality of life (HRQoL), measured by the 15D instrument, and employment status were surveyed among all adult patients alive in 2007 (401 patients). The response rate was 89%. Posttransplant cardiovascular risk factor prevalence and HRQoL were compared with that in the age- and gender-matched Finnish general population. The cumulative risk for chronic kidney disease increased from 10% at 5 years to 16% at 10 years following LT. GFR up to 10 years after LT could be predicted by the GFR at 1 year. In patients transplanted for chronic liver disease, a moderate correlation of pretransplant GFR with later GFR was also evident, whereas in acute liver failure patients after LT, even severe pretransplant renal dysfunction often recovered. By 5 years after LT, 71% of acute liver failure patients were receiving antihypertensive medications, 61% were exhibiting dyslipidemia, 10% were diabetic, 32% were overweight, and 13% obese. Compared with the general population, only hypertension displayed a significantly elevated prevalence among patients – 2.7-fold – whereas patients exhibited 30% less dyslipidemia and 71% less impaired fasting glucose. The cumulative incidence of cancer was 5% at 5 years and 13% at 10. Compared with the general population, patients were subject to a 2.6-fold cancer risk, with non-melanoma skin cancer (standardized incidence ratio, SIR, 38.5) and non-Hodgkin lymphoma (SIR 13.9) being the predominant malignancies. Non-Hodgkin lymphoma was associated with male gender, young age, and the immediate posttransplant period, whereas old age and antibody induction therapy raised skin-cancer risk. HRQoL deviated clinically unimportantly from the values in the general population, but significant deficits among patients were evident in some physical domains. HRQoL did not seem to decrease with longer follow-up. Although 87% of patients reported improved working capacity, data on return to working life showed marked age-dependency: Among patients aged less than 40 at LT, 70 to 80% returned to work, among those aged 40 to 50, 55%, and among those above 50, 15% to 28%. The most common cause for unemployment was early retirement before LT. Those patients employed exhibited better HRQoL than those unemployed. In conclusion, although renal impairment, hypertension, and cancer are evidently common after LT and increase with time, patients’ quality of life remains comparable with that of the general population.

Determinants of outcome in critically ill patients

Assessment of the outcome of critical illness is complex. Severity scoring systems and organ dysfunction scores are traditional tools in mortality and morbidity prediction in intensive care. Their ability to explain risk of death is impressive for large cohorts of patients, but insufficient for an individual patient. Although events before intensive care unit (ICU) admission are prognostically important, the prediction models utilize data collected at and just after ICU admission. In addition, several biomarkers have been evaluated to predict mortality, but none has proven entirely useful in clinical practice. Therefore, new prognostic markers of critical illness are vital when evaluating the intensive care outcome. The aim of this dissertation was to investigate new measures and biological markers of critical illness and to evaluate their predictive value and association with mortality and disease severity. The impact of delay in emergency department (ED) on intensive care outcome, measured as hospital mortality and health-related quality of life (HRQoL) at 6 months, was assessed in 1537 consecutive patients admitted to medical ICU. Two new biological markers were investigated in two separate patient populations: in 231 ICU patients and 255 patients with severe sepsis or septic shock. Cell-free plasma DNA is a surrogate marker of apoptosis. Its association with disease severity and mortality rate was evaluated in ICU patients. Next, the predictive value of plasma DNA regarding mortality and its association with the degree of organ dysfunction and disease severity was evaluated in severe sepsis or septic shock. Heme oxygenase-1 (HO-1) is a potential regulator of apoptosis. Finally, HO-1 plasma concentrations and HO-1 gene polymorphisms and their association with outcome were evaluated in ICU patients. The length of ED stay was not associated with outcome of intensive care. The hospital mortality rate was significantly lower in patients admitted to the medical ICU from the ED than from the non-ED, and the HRQoL in the critically ill at 6 months was significantly lower than in the age- and sex-matched general population. In the ICU patient population, the maximum plasma DNA concentration measured during the first 96 hours in intensive care correlated significantly with disease severity and degree of organ failure and was independently associated with hospital mortality. In patients with severe sepsis or septic shock, the cell-free plasma DNA concentrations were significantly higher in ICU and hospital nonsurvivors than in survivors and showed a moderate discriminative power regarding ICU mortality. Plasma DNA was an independent predictor for ICU mortality, but not for hospital mortality. The degree of organ dysfunction correlated independently with plasma DNA concentration in severe sepsis and plasma HO-1 concentration in ICU patients. The HO-1 -413T/GT(L)/+99C haplotype was associated with HO-1 plasma levels and frequency of multiple organ dysfunction. Plasma DNA and HO-1 concentrations may support the assessment of outcome or organ failure development in critically ill patients, although their value is limited and requires further evaluation.

Long-term outcomes of esophageal atresia

Esophageal atresia (EA), a common congenital anomaly comprising interrupted esophagus with or without a tracheoesophageal fistula (TEF), affects one in 2840 newborns. Over half have associated anomalies. After EA repair in infancy, gastroesophageal reflux (GER) and esophageal dysmotility and respiratory problems are common. As there exist no previous population-based long-term follow-up-studies on EA, its long-term sequelae are unclear. The aims of this study were to assess the cancer incidence (I), esophageal morbidity and function (II), respiratory morbidity (III), and the spinal defects (IV) in adults with repaired EA. All patients treated for EA at the Hospital for Children and Adolescents, University of Helsinki, from 1947 to 1985 were identified, and those alive with their native esophagus were contacted, and the first hundred who replied made up the study group. The patients were interviewed, they filled in symptom questionnaires, and they underwent esophageal endoscopy and manometry, pulmonary function tests, and a full orthopedic evaluation was performed with radiographs of the spine. The questionnaire was also sent by mail to adults with repaired EA not attending the clinical study, and to 287 general population-derived controls matched for age, gender, and municipality of residence. Incidence of cancer among the study population was evaluated from the population-based countrywide cancer registry. 169 (72%) adults with repaired EA replied; 101 (42%) (58 male) participated in the clinical studies at a median age of 36 years (range, 22-56). Symptomatic GER occurred in 34% and dysphagia in 85% of the patients and in 8% and 2% of the controls (P<0.001 for both). The main endoscopic findings included hiatal hernia (28%), Barrett´s esophagus (11%), esophagitis (8%), and stenotic anastomosis (8%). Histology revealed esophagitis in 25 individuals, and epithelial metaplasia in another 21. At immunohistochemistry, CDX2-positive columnar epithelial metaplasia was present in all 21 individuals, and 6 of these also demonstrated goblet cells and MUC2 positivity. In all histological groups, GER and dysphagia were equally common (P=ns). Esophageal manometry demonstrated non-propagating peristalsis in most of the patients, and low ineffective pressure of the distal esophageal body in all. The changes were significantly worse in those with epithelial metaplasia (P≤0.022). Anastomotic complications (OR 8.6-24, 95%CI 1.7-260, P=0.011-0.008), age (OR 20, 95%CI 1.3-310, P=0.034), low distal esophageal body pressure (OR 2.6, 95%CI 0.7-10, P=0.002), and defective esophageal peristalsis (OR 2.2, 95%CI 0.4-11, P=0.014) all predicted development of epithelial metaplasia. Despite the high incidence of esophageal metaplasia, none of the EA patients had suffered esophageal cancer, according to the Finnish Cancer Registry. Although three had had cancer (SIR, 1.0; 95% CI, 0.20-2.8). The overall cancer incidence among adults with repaired EA did not differ from that of the general Finnish population. Current respiratory symptoms occurred in 11% of the patients and 2% of the controls (P<0.001). Of the patients, 16%, and 6% of the controls had doctor-diagnosed asthma (P<0.001). A total of 56% and 70% of the patients and 20% and 50% of the controls had a history of pneumonia and of bronchitis (P<0.001 for both). Respiratory-related impaired quality of life was observable in 11% of the patients in contrast to 6% of the controls (P<0.001). PFT revealed obstruction in 21 of the patients, restriction in 21, and both in 36. A total of 41 had bronchial hyper-responsiveness (BHR) in HCT, and 15 others had an asthma-like response. Thoracotomy-induced rib fusion (OR 3.4, 95%CI 1.3-8.7, P=0.01) and GER-associated epithelial metaplasia in adulthood (OR 3.0, 95%CI 1.0-8.9, P=0.05) were the most significant risk factors for restrictive ventilatory defect. Vertebral anomalies were evident in 45 patients, predominating in the cervical spine in 38. The most significant risk factor for the occurrence of vertebral anomalies was any additional anomaly (OR 27, 95%C I8-100). Scoliosis (over 10 degrees) was observable in 56 patients, over 20 degrees in 11, and over 45 degrees in one. In the EA patients, risk for scoliosis over 10 degrees was 13-fold (OR 13, 95%CI 8.3-21) and over 20 degrees, 38-fold (OR 38, 95%CI 14-106) when compared to that of the general population. Thoracotomy-induced rib fusion (OR 3.6, 95%CI 0.7-19) and other associated anomalies (OR 2.1, 95%CI 0.9-2.9) were the strongest predictive factors for scoliosis. Significant esophageal morbidity associated with EA extends into adulthood. No association existed between the esophageal symptoms and histological findings. Surgical complications, increasing age, and impaired esophageal motility predicted development of epithelial metaplasia after repair of EA. According to our data, the risk for esophageal cancer is less than 500-fold that of the general population. However, the overall cancer incidence among adults with repaired EA did not differ from that of the general population. Adults with repaired EA have had significantly more respiratory symptoms and infections, as well as more asthma, and allergies than does the general population. Thoracotomy-induced rib fusion and GER-associated columnar epithelial metaplasia were the most significant risk factors for the restrictive ventilatory defect that occurred in over half the patients. Over half the patients with repaired EA are likely to develop scoliosis. Risk for scoliosis is 13-fold after repair of EA in relation to that of the general population. Nearly half the patients had vertebral anomalies. Most of these deformities were diagnosed neither in infancy nor during growth. The natural history of spinal deformities seems, however, rather benign, with spinal surgery rarely indicated.

Outcomes of ruptured abdominal aortic aneurysm

Ruptured abdominal aortic aneurysm (RAAA) is a life-threatening event, and without operative treatment the patient will die. The overall mortality can be as high as 80-90%; thus repair of RAAA should be attempted whenever feasible. The quality of life (QoL) has become an increasingly important outcome measure in vascular surgery. Aim of the study was to evaluate outcomes of RAAA and to find out predictors of mortality. In Helsinki and Uusimaa district 626 patients were identified to have RAAA in 1996-2004. Altogether 352 of them were admitted to Helsinki University Central Hospital (HUCH). Based on Finnvasc Registry, 836 RAAA patients underwent repair of RAAA in 1991-1999. The 30-day operative mortality, hospital and population-based mortality were assessed, and the effect of regional centralisation and improving in-hospital quality on the outcome of RAAA. QoL was evaluated by a RAND-36 questionnaire of survivors of RAAA. Quality-adjusted life years (QALYs), which measure length and QoL, were calculated using the EQ-5D index and estimation of life expectancy. The predictors of outcome after RAAA were assessed at admission and 48 hours after repair of RAAA. The 30-day operative mortality rate was 38% in HUCH and 44% nationwide, whereas the hospital mortality was 45% in HUCH. Population-based mortality was 69% in 1996-2004 and 56% in 2003-2004. After organisational changes were undertaken, the mortality decreased significantly at all levels. Among the survivors, the QoL was almost equal when compared with norms of age- and sex-matched controls; only physical functioning was slightly impaired. Successful repair of RAAA gave a mean of 4.1 (0-30.9) QALYs for all RAAA patients, although non-survivors were included. The preoperative Glasgow Aneurysm Score was an independent predictor of 30-day operative mortality after RAAA, and it also predicted the outcome at 48- hours for initial survivors of repair of RAAA. A high Glasgow Aneurysm Score and high age were associated with low numbers of QALYs to be achieved. Organ dysfunction measured by the Sequential Organ Failure Assessment (SOFA) score at 48 hours after repair of RAAA was the strongest predictor of death. In conclusion surgery of RAAA is a life-saving and cost-effective procedure. The centralisation of vascular emergencies improved the outcome of RAAA patients. The survivors had a good QoL after RAAA. Predictive models can be used on individual level only to provide supplementary information for clinical decision-making due to their moderate discriminatory value. These results support an active operation policy, as there is no reliable measure to predict the outcome after RAAA.

Functional Outcome after Free Flap Reconstructions in Oral and Pharyngeal Cancer

Oral cancer ranks among the 10 most common cancers worldwide. Since it is commonly diagnosed at locally advanced stage, curing the cancer demands extensive tissue resection. The emergent defect is reconstructed generally with a free flap transfer. Repair of the upper aerodigestive track with maintenance of its multiform activities is challenging. The aim of the study was to extract comprehensive treatment outcomes for patients having undergone microvascular free flap transfer because of large oral cavity or pharyngeal cancer. Ninety-four patients were analyzed for postoperative survival and complications. Forty-four patients were followed-up and analyzed for functional outcome, which was determined in terms of quality of life, speech, swallowing, and intraoral sensation. Quality of life was assessed using the University of Washington Head and Neck Questionnaire. Speech was analyzed for aerodynamic parameters and for nasal acoustic energy, as well as perceptually for articulatory proficiency, voice quality, and intelligibility. Videofluorography was performed to determine the swallowing ability. Intraoral sensation was measured by moving 2-point discrimination. The 3-year overall survival was over 40%. The 1-year disease-free survival was 43%. Postoperative complications arose in over half of the patients. Flap success rate was high. Perioperative mortality varied between 2% and 11%. Unemployment and heavy drinking were the strongest predictors of survival. Sociodemographic factors were found to associate with quality of life. The global quality of life score deteriorated and did not return to the preoperative level. Significant reduction was detectable in the domains measuring chewing and speech, and in appearance and shoulder function. The basic elements necessary for normal speech were maintained. Speech intelligibility reduced and was related to the misarticulations of the /r/ and /s/ phonemes. Deviant /r/ and /s/ persisted in most patients. Hoarseness and hypernasality occurred infrequently. One year postoperatively, 98% of the patients had achieved oral nutrition and half of them were on a regular masticated diet. Overt and silent aspiration was encountered throughout the follow-up. At 12-month swallow test, 44% of the patients aspirated, 70% of whom silently. Of these patients, 15% presented with pulmonary changes referring to aspiration. Intraoral sensation weakened but was unrelated to oral functions. The results provide new data for oral reconstructions and highlight the importance of the functional outcome of the treatment for an oral cancer patient. The mouth and the pharynx encompass a unit of utmost functional complexity. Surgery should continue to make progress in this area, and methods that lead to good function should be developed. Operational outcome should always be evaluated in terms of function.

Effects of unilateral vocal fold paralysis treatment with fascia augmentation on airflow mechanics, tracheal sounds and voice acoustics

Data on the influence of unilateral vocal fold paralysis on breathing, especially other than information obtained by spirometry, are relatively scarce. Even less is known about the effect of its treatment by vocal fold medialization. Consequently, there was a need to study the issue by combining multiple instruments capable of assessing airflow dynamics and voice. This need was emphasized by a recently developed medialization technique, autologous fascia injection; its effects on breathing have not previously been investigated. A cohort of ten patients with unilateral vocal fold paralysis was studied before and after autologous fascia injection by using flow-volume spirometry, body plethysmography and acoustic analysis of breathing and voice. Preoperative results were compared with those of ten healthy controls. A second cohort of 11 subjects with unilateral vocal fold paralysis was studied pre- and postoperatively by using flow-volume spirometry, impulse oscillometry, acoustic analysis of voice, voice handicap index and subjective assessment of dyspnoea. Preoperative peak inspiratory flow and specific airway conductance were significantly lower and airway resistance was significantly higher in the patients than in the healthy controls (78% vs. 107%, 73% vs. 116% and 182% vs. 125% of predicted; p = 0.004, p = 0.004 and p = 0.026, respectively). Patients had a higher root mean square of spectral power of tracheal sounds than controls, and three of them had wheezes as opposed to no wheezing in healthy subjects. Autologous fascia injection significantly improved acoustic parameters of the voice in both cohorts and voice handicap index in the latter cohort, indicating that this procedure successfully improved voice in unilateral vocal fold paralysis. Peak inspiratory flow decreased significantly as a consequence of this procedure (from 4.54 ± 1.68 l to 4.21 ± 1.26 l, p = 0.03, in pooled data of both cohorts), but no change occurred in the other variables of flow-volume spirometry, body-plethysmography and impulse oscillometry. Eight of the ten patients studied by acoustic analysis of breathing had wheezes after vocal fold medialization compared with only three patients before the procedure, and the numbers of wheezes per recorded inspirium and expirium increased significantly (from 0.02 to 0.42 and from 0.03 to 0.36; p = 0.028 and p = 0.043, respectively). In conclusion, unilateral vocal fold paralysis was observed to disturb forced breathing and also to cause some signs of disturbed tidal breathing. Findings of flow volume spirometry were consistent with variable extra-thoracic obstruction. Vocal fold medialization by autologous fascia injection improved the quality of the voice in patients with unilateral vocal fold paralysis, but also decreased peak inspiratory flow and induced wheezing during tidal breathing. However, these airflow changes did not appear to cause significant symptoms in patients.

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.

The incidence and outcome of severe sepsis in Finland : The Finnsepsis Study

Severe sepsis is associated with common occurrence, high costs of care and significant mortality. The incidence of severe sepsis has been reported to vary between 0.5/1000 and 3/1000 in different studies. The worldwide Severe Sepsis Campaign, guidelines and treatment protocols aim at decreasing severe sepsis associated high morbidity and mortality. Various mediators of inflammation, such as high mobility group box-1 protein (HMGB1) and vascular endothelial growth factor (VEGF), have been tested for severity of illness and outcome in severe sepsis. Long-term survival with quality of life (QOL) assessment is important outcome after severe sepsis. The objective of this study was to evaluate the incidence, severity of organ dysfunction and outcome of severe sepsis in intensive care treated patients in Finland (study I)). HMGB1 and VEGF were studied in predicting severity of illness, development and type of organ dysfunction and hospital mortality (studies II and III). The long-term outcome and quality of life were assessed and quality-adjusted life years and cost per one QALY were estimated (study IV). A total of 470 patients with severe sepsis were included in the Finnsepsis Study. Patients were treated in 24 Finnish intensive care units in a 4-month period from 1 November 2004 to 28 February 2005. The incidence of severe sepsis was 0.38 /1,000 in the adult population (95% confidence interval 0.34-0.41). Septic shock (77%), severe oxygenation impairment (71.4%) and acute renal failure (23.2%) were the most common organ failures. The ICU, hospital, one-year and two-year mortalities were 15.5%, 28.3%, 40.9% and 44.9% respectively. HMGB1 and VEGF were elevated in patients with severe sepsis. VEGF concentrations were lower in non-survivors than in survivors, but HMGB1 levels did not differ between patients. Neither HMGB1 nor VEGF were predictive of hospital mortality. The QOL was measured median 17 months after severe sepsis and QOL was lower than in reference population. The mean QALY was 15.2 years for a surviving patient and the cost for one QALY was 2,139 . The study showed that the incidence of severe sepsis is lower in Finland than in other countries. The short-term outcome is comparable with that in other countries, but long-term outcome is poor. HMGB1 and VEGF are not useful in predicting mortality in severe sepsis. The mean QALY for a surviving patient is 15.2 and as the cost for one QALY is reasonably low, the intensive care is cost-effective in patients with severe sepsis.

Studies on the assessment of the adequacy of anesthesia

Several hypnosis monitoring systems based on the processed electroencephalogram (EEG) have been developed for use during general anesthesia. The assessment of the analgesic component (antinociception) of general anesthesia is an emerging field of research. This study investigated the interaction of hypnosis and antinociception, the association of several physiological variables with the degree of intraoperative nociception, and aspects of EEG Bispectral Index Scale (BIS) monitoring during general anesthesia. In addition, EEG features and heart rate (HR) responses during desflurane and sevoflurane anesthesia were compared. A propofol bolus of 0.7 mg/kg was more effective than an alfentanil bolus of 0.5 mg in preventing the recurrence of movement responses during uterine dilatation and curettage (D C) after a propofol-alfentanil induction, combined with nitrous oxide (N2O). HR and several HR variability-, frontal electromyography (fEMG)-, pulse plethysmography (PPG)-, and EEG-derived variables were associated with surgery-induced movement responses. Movers were discriminated from non-movers mostly by the post-stimulus values per se or normalized with respect to the pre-stimulus values. In logistic regression analysis, the best classification performance was achieved with the combination of normalized fEMG power and HR during D C (overall accuracy 81%, sensitivity 53%, specificity 95%), and with the combination of normalized fEMG-related response entropy, electrocardiography (ECG) R-to-R interval (RRI), and PPG dicrotic notch amplitude during sevoflurane anesthesia (overall accuracy 96%, sensitivity 90%, specificity 100%). ECG electrode impedances after alcohol swab skin pretreatment alone were higher than impedances of designated EEG electrodes. The BIS values registered with ECG electrodes were higher than those registered simultaneously with EEG electrodes. No significant difference in the time to home-readiness after isoflurane-N2O or sevoflurane-N2O anesthesia was found, when the administration of the volatile agent was guided by BIS monitoring. All other early and intermediate recovery parameters were also similar. Transient epileptiform EEG activity was detected in eight of 15 sevoflurane patients during a rapid increase in the inspired volatile concentration, and in none of the 16 desflurane patients. The observed transient EEG changes did not adversely affect the recovery of the patients. Following the rapid increase in the inhaled desflurane concentration, HR increased transiently, reaching its maximum in two minutes. In the sevoflurane group, the increase was slower and more subtle. In conclusion, desflurane may be a safer volatile agent than sevoflurane in patients with a lowered seizure threshold. The tachycardia induced by a rapid increase in the inspired desflurane concentration may present a risk for patients with heart disease. Designated EEG electrodes may be superior to ECG electrodes in EEG BIS monitoring. When the administration of isoflurane or sevoflurane is adjusted to maintain BIS values at 50-60 in healthy ambulatory surgery patients, the speed and quality of recovery are similar after both isoflurane-N2O and sevoflurane-N2O anesthesia. When anesthesia is maintained by the inhalation of N2O and bolus doses of propofol and alfentanil in healthy unparalyzed patients, movement responses may be best avoided by ensuring a relatively deep hypnotic level with propofol. HR/RRI, fEMG, and PPG dicrotic notch amplitude are potential indicators of nociception during anesthesia, but their performance needs to be validated in future studies. Combining information from different sources may improve the discrimination of the level of nociception.

Randomised Evaluation of New Technologies within the Population‐Based Cervical Cancer Screening Programme in Finland: Cross‐Sectional Performance and Validity

A randomised and population-based screening design with new technologies has been applied to the organised cervical cancer screening programme in Finland. In this experiment the women invited to routine five-yearly screening are individually randomised to be screened with automation-assisted cytology, human papillomavirus (HPV) test or conventional cytology. By using the randomised design, the ultimate aim is to assess and compare the long-term outcomes of the different screening regimens. The primary aim of the current study was to evaluate, based on the material collected during the implementation phase of the Finnish randomised screening experiment, the cross-sectional performance and validity of automation-assisted cytology (Papnet system) and primary HPV DNA testing (Hybrid Capture II assay for 13 oncogenic HPV types) within service screening, in comparison to conventional cytology. The parameters of interest were test positivity rate, histological detection rate, relative sensitivity, relative specificity and positive predictive value. Also, the effect of variation in performance by screening laboratory on age-adjusted cervical cancer incidence was assessed. Based on the cross-sectional results, almost no differences were observed in the performance of conventional and automation-assisted screening. Instead, primary HPV screening found 58% (95% confidence interval 19-109%) more cervical lesions than conventional screening. However, this was mainly due to overrepresentation of mild- and moderate-grade lesions and, thus, is likely to result in overtreatment since a great deal of these lesions would never progress to invasive cancer. Primary screening with an HPV DNA test alone caused substantial loss in specificity in comparison to cytological screening. With the use of cytology triage test, the specificity of HPV screening improved close to the level of conventional cytology. The specificity of primary HPV screening was also increased by increasing the test positivity cutoff from the level recommended for clinical use, but the increase was more modest than the one gained with the use of cytology triage. The performance of the cervical cancer screening programme varied widely between the screening laboratories, but the variation in overall programme effectiveness between respective populations was more marginal from the very beginning of the organised screening activity. Thus, conclusive interpretations on the quality or success of screening should not be based on performance parameters only. In the evaluation of cervical cancer screening the outcome should be selected as closely as possible to the true measure of programme effectiveness, which is the number of invasive cervical cancers and subsequent deaths prevented in the target population. The evaluation of benefits and adverse effects of each new suggested screening technology should be performed before the technology becomes an accepted routine in the existing screening programme. At best, the evaluation is performed randomised, within the population and screening programme in question, which makes the results directly applicable to routine use.