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There are substantial concerns about impaired honey bee health and colony losses due to several poorly understood factors. We used MALDI profiling (MALDI BeeTyping®) analysis to investigate how some environmental and management factors under field conditions across Europe affected the honey bee haemolymph peptidome (all peptides in the circulatory fluid), as a profile of molecular markers representing the immune status of Apis mellifera. Honey bees were exposed to a range of environmental stressors in 128 agricultural sites across eight European countries in four biogeographic zones, with each country contributing eight sites each for two different cropping systems: oilseed rape (OSR) and apple (APP). The full haemolymph peptide profiles, including the presence and levels of three key immunity markers, namely the antimicrobial peptides (AMPs) Apidaecin, Abaecin and Defensin-1, allowed the honey bee responses to environmental variables to be discriminated by country, crop type and site. When considering just the AMPs, it was not possible to distinguish between countries by the prevalence of each AMP in the samples. However, it was possible to discriminate between countries on the amounts of the AMPs, with the Swedish samples in particular expressing high amounts of all AMPs. A machine learning model was developed to discriminate the haemolymphs of bees from APP and OSR sites. The model was 90.6 % accurate in identifying the crop type from the samples used to build the model. Overall, MALDI BeeTyping® of bee haemolymph represents a promising and cost-effective "blood test" for simultaneously monitoring dozens of peptide markers affected by environmental stressors at the landscape scale, thus providing policymakers with new diagnostic and regulatory tools for monitoring bee health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Older adults have complex medical needs that causes increased use of resources at the emergency department (ED). The prevalence of non-specific complaint (NSC) as a chief-complaint in the ED is common among older adults and is not prioritized even though possibly having worse clinical outcome. The objective was to study hospital admission and mortality for older adults visiting the ED with NSC compared to specific complaints such as dyspnea, chest pain and abdominal pain., Methods: A retrospective observational study of older adults visiting the ED with NSC and specific complaints; dyspnea, chest pain and abdominal pain was performed. Chief-complaint were collected from electronic medical records. Fatigue, confusion, non-specific complaints, generalized weakness and risk of falling were defined as non-specific complaint (NSC) when registered as chief-complaint at the ED. Admission rate and 30-days mortality were the primary outcomes., Results: A total of 4927 patients were included in the study based on chief-complaint; patients with chest pain 1599 (32%), dyspnea 1343 (27%), abdominal pain 1460 (30%) and NSC 525 (11%). Patients with dyspnea and NSC had the highest hospital admission rate 79% vs 70% compared to patients with chest pain (63%) and abdominal pain (61%) (p =  < 0.001). Patients with NSC had a mean LOS 4.7 h at the ED which was significantly higher compared to chest pain, dyspnea and abdominal pain. Mean bed-days for the whole population was 4.2 days compared to patients with NSC who had a mean LOS of 5.6 days. NSC and dyspnea were both associated with the highest 30-day mortality., Conclusion: Older patients who present with NSC at the ED are associated with a high risk for admission and 30-days mortality. In addition, patients with NSC have a longer LOS at the ED, a high admission rate and the highest number of bed-days once admitted. This study indicates that ED staff should be more vigilant when an elderly patient presents with NSC at the ED. Further studies and guidelines are needed to improve the management of these individuals., (© 2023. The Author(s).)

Background: Contemporary patients with primary hyperparathyroidism are often diagnosed with mildly raised serum calcium levels. Previous studies have reported increased mortality in patients with primary hyperparathyroidism. This retrospective cohort study aimed to examine whether contemporary patients operated for primary hyperparathyroidism have higher mortality than the general population, and whether mortality in these patients is associated with serum calcium concentration, adenoma weight or multiglandular disease., Methods: Patients from a Swedish national cohort consisting of patients registered in the Scandinavian Quality Register for Thyroid, Parathyroid, and Adrenal Surgery 2003-2013, were matched with population controls. The National Patient Register, the Swedish Cause of Death Register, and socioeconomic data were cross-linked. End of follow-up was 10 years after surgery, 31 December 2015, or emigration. Mortality was analysed by standardized mortality ratio, Kaplan-Meier survival estimates, and univariable and multivariable Cox regression. Multiple imputation by chained equations was performed on missing data., Results: After exclusions, there were 5009 patients with primary hyperparathyroidism and 14 983 controls. Multivariable Cox regression analysis adjusted for age, sex, Charlson Co-morbidity Index, marital status, level of education, disposable income, and period of surgery showed lower mortality in patients than controls (hazard ratio (HR) 0.83, 95 per cent c.i. 0.75 to 0.92). In univariable Cox regression of mortality in patients, serum calcium concentration (mmoles per litre) was associated with mortality (HR 2.20, 1.53 to 3.16). This association remained in multivariable Cox regression after multiple imputation (HR 1.79, 1.19 to 2.70)., Conclusion: Mortality was not increased in patients operated for primary hyperparathyroidism compared with controls in a contemporary setting. Preoperative serum calcium concentration might, however, influence survival., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.)

Background: Patients on home hemodialysis (HHD) exhibit superior survival compared with patients on institutional hemodialysis (IHD) and peritoneal dialysis (PD). There is a sparsity of reports comparing morbidity between HHD and IHD or PD and none in a European population. The aim of this study is to compare morbidity between modalities in a Swedish population., Methods: The Swedish Renal Registry was used to retrieve patients starting on HHD, IHD or PD. Patients were matched according to sex, age, comorbidity and start date. The Swedish Inpatient Registry was used to determine comorbidity before starting renal replacement therapy (RRT) and hospital admissions during RRT. Dialysis technique survival was compared between HHD and PD., Results: RRT was initiated with HHD for 152 patients; these were matched with 608 patients with IHD and 456 with PD. Patients with HHD had significantly lower annual admission rate and number of days in hospital. (median 1.7 admissions; 12 days) compared with IHD (2.2; 14) and PD (2.8; 20). The annual admission rate was significantly lower for patients with HHD compared with IHD for cardiovascular diagnoses and compared with PD for infectious disease diagnoses. Dialysis technique survival was significantly longer with HHD compared with PD., Conclusions: Patients choosing HHD as initial RRT spend less time in hospital compared with patients on IHD and PD and they were more likely than PD patients, to remain on their initial modality. These advantages, in combination with better survival and higher likelihood of renal transplantation, are important incentives for promoting the use of HHD.

For a long time the attention given to the hip fracture patient group was minor and without any certain consideration to their frailty. To improve the care for these patients Skane University Hospital in Lund has during the past 19 years worked actively with developing the care. This paper aims to describe what impact the care process development has had on functional outcome and mortality, as well as to analyze the impact of comorbidity and fracture type., Methods: Patients older than 50 years with non-pathological cervical and trochanteric hip fracture admitted between Jan 1st 1999 and Dec 31st 2017 were included and data was retrieved from the National Quality Register for hip fracture patients, RIKSHÖFT. Variables regarding patient characteristics, fracture type, operation method, lead-times and outcome were analyzed. For comparison Fischer's exact test and Spearman's rank correlation coefficient was used for the categorical data and Pearson correlation coefficient for the continuous. To further analyze the effect over time a linear regression model was used., Results: A total of 7827 patients were included. A significant shift in the overall morbidity was seen, with an increase in patients of higher ASA grade. No correlation was seen between outcome and the care process development. The mortality rate for the group as a whole the mortality rate had decreased over time. The total length of stay had decreased significantly over time. There was no statistically significant change in mortality rate over time when relating it to time-to-surgery., Conclusions: Although the patients display a higher morbidity over time, the mortality rate has not changed significantly, which might indicate an effect of the care process development. The care process development does not seem to impact on outcome as much as other factors. This study supports the possibility to create a more specific algorithm for hip fracture patients, taking specific subgroups into consideration.

Background: The survival rate for dialysis patients is poor. Previous studies have shown improved survival with home hemodialysis (HHD), but this could be due to patient selection, since HHD patients tend to be younger and healthier. The aim of the present study is to analyse the long-term effects of HHD on patient survival and on subsequent renal transplantation, compared with institutional hemodialysis (IHD) and peritoneal dialysis (PD), taking age and comorbidity into account., Methods: Patients starting HHD as initial renal replacement therapy (RRT) were matched with patients on IHD or PD, according to gender, age, Charlson Comorbidity Index and start date of RRT, using the Swedish Renal Registry from 1991 to 2012. Survival analyses were performed as intention-to-treat (disregarding changes in RRT) and per-protocol (as on initial RRT)., Results: A total of 152 patients with HHD as initial RRT were matched with 608 IHD and 456 PD patients, respectively. Median survival was longer for HHD in intention-to-treat analyses: 18.5 years compared with 11.9 for IHD (p <  0.001) and 15.0 for PD (p = 0.002). The difference remained significant in per-protocol analyses omitting the contribution of subsequent transplantation. Patients on HHD were more likely to receive a renal transplant compared with IHD and PD, although treatment modality did not affect subsequent graft survival (p > 0.05)., Conclusion: HHD as initial RRT showed improved long-term patient survival compared with IHD and PD. This survival advantage persisted after matching and adjusting for a higher transplantation rate. Dialysis modality had no impact on subsequent graft survival.

Background: It remains unclear whether total or subtotal parathyroidectomy for secondary hyperparathyroidism yields the best outcomes. We investigated mortality, cardiovascular events, hip fracture, and recurrent parathyroidectomy after total versus subtotal parathyroidectomy in patients on renal replacement therapy., Methods: Using the Swedish Renal Registry, the surgical registry for thyroid and parathyroid surgery, and the National Inpatient Registry, we identified patients who underwent parathyroidectomy between 1991 and 2013. We calculated the risk of outcome after total versus subtotal parathyroidectomy using COX's regression, adjusting for age, sex, cause of renal disease, time with a functioning graft before and after parathyroidectomy, Charlson comorbidity index, year of surgery, prevalent cardiovascular disease, time on dialysis, renal transplantation at parathyroidectomy, and treatment with calcimimetics before parathyroidectomy., Results: There were 824 patients who underwent parathyroidectomy, 388 total and 436 subtotal. There was no difference in mortality or risk of incident hip fracture between groups. Comparing the subtotal with the total parathyroidectomy, the adjusted hazard ratio (95% confidence interval) for cardiovascular events was 0.43 (0.25-0.72) and for recurrent parathyroidectomy 3.33 (1.33-8.32)., Conclusion: There was a higher risk of cardiovascular events in patients after total parathyroidectomy compared with subtotal parathyroidectomy, but a lower risk of recurrent parathyroidectomy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Nearly 18,000 individuals suffer from hip fracture in Sweden each year. The choice in operation method for femoral neck fractures has changed over the years as well as the overall management. Functional outcome after hip fracture is affected by several factors and the overall functional level for old people in Sweden has improved over the last decades., Objective: To describe and analyse the functional outcome and choice of operation method for hip fracture patients between 1988 and 2012., Patients and Methods: All patients with cervical or trochanteric hip fracture treated at Lund University Hospital from 1988 until 2012 were collected from the National Quality Register for hip fracture patients, RIKSHÖFT. Patients younger than 50 years and those with pathological fractures were excluded. Data regarding patient characteristics, fracture type, operation method and housing, walking ability and use of walk aids prefracture and at 4-months follow-up was retrieved and analysed., Results: For this study 8723 patients were included with a mean age of 81.6 (men 79.3, women 82.5). The mean age significantly increased over the period studied. Sliding hip screw dominates as method of choice for the trochanteric fractures. For the cervical fractures there is a clear shift from osteosynthesis to arthroplasty. There is a significant decrease in functional outcome at follow-up compared to prefracture. No significant trend change can be seen over 25 years. Functional outcome are worse for the patients with trochanteric fracture., Conclusion: Although there have been changes in operation methods for hip fractures and the management has developed, our study does not show any effect on functional outcome over a 25-year period. The medical condition of these patients with increasing age seems to counteract efforts to improve the care., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Permanent hypoparathyroidism remains the most common adverse outcome after total thyroidectomy, but long-term effects of hypoparathyroidism are unknown. The aim was to investigate mortality in patients with permanent hypoparathyroidism after total thyroidectomy., Methods: Data from the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal Surgery were linked with the Swedish National Prescription Register for Pharmaceuticals and the Swedish National Inpatient Register. Patients who underwent total thyroidectomy between 1 July 2005 and 30 June 2014 for benign thyroid disease, and who used active vitamin D for at least 6 months after surgery, were classified as having permanent hypoparathyroidism and included in the study cohort. Risk of death was assessed using Cox regression analysis, adjusting for age, sex, thyrotoxicosis and co-morbidity., Results: There were 4899 patients, with a mean(s.d.) age of 46·3(15·8) years; 83·1 per cent were women, and 2932 patients (59·8 per cent) had thyrotoxicosis. In all, 246 patients (5·2 per cent) were classified as having permanent hypoparathyroidism. Mean(s.d.) follow-up was 4·4(2·4) years, and 109 patients (2·2 per cent) died during follow-up. Compared with patients without permanent hypoparathyroidism, the risk of death was significantly higher among patients with permanent hypoparathyroidism after total thyroidectomy (adjusted hazard ratio 2·09, 95 per cent c.i. 1·04 to 4·20)., Conclusion: Permanent hypoparathyroidism after total thyroidectomy for benign disease is common and associated with an increased risk of death., (© 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Background: Secondary hyperparathyroidism increases the risk for fractures. Despite improvement in medical therapy, surgical parathyroidectomy (PTX) often becomes necessary, but its effect on risk of fractures is not clear. Our aim was to study the effect of parathyroidectomy on the risk of hip fractures in patients on dialysis or with a functioning renal graft at time of parathyroidectomy., Design: In a cohort of 20,056 patients on dialysis or with functioning renal allograft, we identified 590 patients who underwent parathyroidectomy between 1991 and 2009. Of these, 579 were matched with 1970 non-PTX patients on age, sex, cause of renal disease and functioning renal allograft or not at the time of PTX or at the corresponding time for non-PTX patients (t). We calculated the risk for hip fracture after PTX using crude and adjusted Cox proportional hazards regressions, adjusting for time in renal replacement therapy before t, time with functioning renal allograft before and after t, comorbidity at t and a hip fracture before t., Results: The adjusted hazard ratio (95% confidence interval) for hip fracture was 0.40 (0.18-0.88) for PTX patients, compared to non-PTX patients. When analyses were performed separately for sex, only women had a lower risk of hip fracture after PTX compared to non-PTX patients. The risk of hip fracture after PTX was similar in patients with or without functioning renal allograft at time for PTX., Conclusion: Parathyroidectomy is associated with a lower risk of hip fracture in female patients with secondary hyperparathyroidism.

Background: Emergency department (ED) overcrowding is frequently described in terms of input- throughput and output. In order to reduce ED input, a concept called primary triage has been introduced in several Swedish EDs. In short, primary triage means that a nurse separately evaluates patients who present in the Emergency Department (ED) and either refers them to primary care or discharges them home, if their complaints are perceived as being of low acuity. The aim of the present study is to elucidate whether high levels of in-hospital bed occupancy are associated with decreased permeability in primary triage. The appropriateness of discharges from primary triage is assessed by 72-h revisits to the ED., Methods: The study is a retrospective cohort study on administrative data from the ED at a 420-bed hospital in southern Sweden from 2011-2012. In addition to crude comparisons of proportions experiencing each outcome across strata of in-hospital bed occupancy, multivariate models are constructed in order to adjust for age, sex and other factors., Results: A total of 37,129 visits to primary triage were included in the study. 53.4 % of these were admitted to the ED. Among the cases referred to another level of care, 8.8 % made an unplanned revisit to the ED within 72 h. The permeability of primary triage was not decreased at higher levels of in-hospital bed occupancy. Rather, the permeability was slightly higher at occupancy of 100-105 % compared to <95 % (OR 1.09 95 % CI 1.02-1.16). No significant association between in-hospital bed occupancy and the probability of 72-h revisits was observed., Conclusions: The absence of a decreased permeability of primary triage at times of high in-hospital bed occupancy is reassuring, as the opposite would have implied that patients might be denied entry not only to the hospital, but also to the ED, when in-hospital beds are scarce.

Ageing populations and higher ambitions continuously drive healthcare costs in Sweden and worldwide. During the last two decades, downsizing hospital bed capacity has been the strategy for cutting expenditure in the Swedish healthcare system. However, the lack of implementation of new and viable outpatient alternatives has led to a widespread overcrowding problem in Swedish hospitals and emergency departments. The present study was conducted as a survey in hospital wards at two emergency hospitals in southwestern Sweden. Study aims were to assess the causes of hospitalization and indications for continuing in-hospital care in hospitalized geriatric patients (>80 years). The study shows that a very small number of patients are admitted barely because of social factors; however, there is a significant group where hospitalization is due to both social and medical factors. A large group of hospitalized patients over 80 year (37%) could receive their care outside the emergency hospital. About 30% of hospitalized patients are waiting for planning, and the majority of them waiting for social action and planning. Older patients with multiple diseases require healthcare but not hospitalization to the present extent. We should focus on developing additional forms of healthcare since avoidable hospitalization is a high cost for the society, but above all a risk for the individual.

Background: Previous work has suggested that given a hospital's need to admit more patients from the emergency department (ED), high inpatient bed occupancy may encourage premature hospital discharges that favor the hospital's need for beds over patients' medical interests. We argue that the effects of such action would be measurable as a greater proportion of unplanned hospital readmissions among patients discharged when the hospital was full than when not. In response, the present study tested this hypothesis by investigating the association between inpatient bed occupancy at the time of hospital discharge and the 30-day readmission rate., Methods: The sample included all inpatient admissions from the ED at a 420-bed emergency hospital in southern Sweden during 2011-2012 that resulted in discharge before 1 December 2012. The share of unplanned readmissions within 30 days was computed for levels of inpatient bed occupancy of <95%, 95-100%, 100-105% and >105% at the hour of discharge. A binary logistic regression model was constructed to adjust for age, time of discharge, and other factors that could affect the outcome., Results: In all, 32,811 visits were included in the study, 9.9% of which resulted in an unplanned readmission within 30 days of discharge. The proportion of readmissions was 9.0% for occupancy levels of <95% at the patient's discharge, 10.2% for 95-100% occupancy, 10.8% for 100-105% occupancy, and 10.5% for >105% occupancy (p = 0.0001). Results from the multivariate models show that the OR (95% CI) of readmission was 1.11 (1.01-1.22) for patients discharged at 95-100% occupancy, 1.17 (1.06-1.29) at 100-105% occupancy, and 1.15 (0.99-1.34) at >105% occupancy., Conclusions: Results indicate that patients discharged from inpatient wards at times of high inpatient bed occupancy experience an increased risk of unplanned readmission within 30 days of discharge.

Background: Also known as access block, shortage of inpatient beds is a common cause of emergency department (ED) boarding and overcrowding, which are both associated with impaired quality of care. Recent studies have suggested that access block not simply causes boarding in EDs, but may also result in that patients are less likely to be admitted to the hospital from the ED. The present study's aim was to investigate whether this effect remained for patients with acute abdominal pain, for which different management strategies have emerged. Access block was defined in terms of hospital occupancy and the appropriateness of ED discharges addressed as 72 h revisits to the ED., Methods: As a registry study of ED administrative data, the study examined a population of patients who presented with acute abdominal pain at the ED of a 420-bed hospital in southern Sweden during 2011-2013. Associations between exposure and outcomes were addressed in contingency tables and by logistic regression models., Results: Crude analysis revealed a negative association between access block and the probability of inpatient admission (38.6 % admitted at 0-95 % occupancy, 37.8 % at 95-100 % occupancy, and 35.0 % at ≥ 100 % occupancy) (p < .001). No significant associations between exposure and 72 h revisits emerged. Multivariable models indicated an odds ratio of inpatient admission of 0.992 (95 % CI: 0.986-0.997) per percentage increase in hospital occupancy., Conclusions: Study findings indicate that patients with acute abdominal pain are less likely to be admitted to the hospital from the ED at times of access block and that other management strategies are employed instead. No association with 72 h revisits was seen, but future studies need to address more granular outcomes in order to clarify the safety aspects of the effect.

Background: A possible downstream effect of high in-hospital bed occupancy is that patients in the emergency department (ED) who would benefit from in-hospital care are denied admission. The present study aimed at evaluating this hypothesis through investigating associations between in-hospital bed occupancy at the time of presentation in the ED and the probability for unplanned 72-hour (72-h) revisits to the ED among patients discharged at index. A second outcome was unplanned 72-h revisits resulting in admission., Methods: All visits to the ED of a 420-bed emergency hospital in southern Sweden between 1 January 2011 and 31 December 2012, which did not result in admission, death, or transfer to another hospital were included. Revisiting fractions were computed for in-hospital occupancy intervals <85%, 85% to 90%, 90% to 95%, 95% to 100%, 100% to 105%, and ≥105%. Multivariate models were constructed in an attempt to take confounding factors from, e.g., presenting complaints, age, referral status, and triage priority into account., Results: Included in the study are 81,878 visits. The fraction of unplanned 72-h revisits/unplanned 72-h revisits resulting in admission was 5.8%/1.4% overall, 6.2%/1.4% for occupancy <85%, 6.4%/1.5% for occupancy 85% to 90%, 5.8%/1.4% for occupancy 90% to 95%, 6.0%/1.6% for occupancy 95% to 100%, 5.4%/1.6% for occupancy 100% to 105%, and 4.9%/1.4% for occupancy ≥105%. In the multivariate models, a trend to lower probability of unplanned 72-h revisits was observed at occupancy ≥105% compared to occupancy <95% (OR 0.88, CI 0.76 to 1.01). No significant associations between in-hospital occupancy at index and the probability of making unplanned 72-h revisits resulting in admission were observed., Conclusions: The lack of associations between in-hospital occupancy and unplanned 72-h revisits does not support the hypothesis that ED patients are inappropriately discharged when in-hospital beds are scarce. The results are reassuring as they indicate that physicians are able to make good decisions, also while resources are constrained.

Background: In 2005, the Advanced Life Support (ALS) teams delivering pre-hospital care in RegionSkane in southern Sweden received additional support by physicians, who were part of "Pre-hospital acute teams" (PHAT). The study objective is to compare the incidence of pre-hospital medical interventions for trauma-patients cared for by conventional ALS teams and patients who received additional support by PHAT., Methods: Trauma patients with Injury Severity Score (ISS) >9 were identified retrospectively in the national quality registry KVITTRA at three hospitals in RegionSkane, for the time period October 2005 to December 2008. Interventions include e.g. tracheal intubation, administration of i.v. fluids, neck immobilization and spine board usage. Confounding effects from trauma severity, trauma mechanism, vital parameters, age and sex were addressed in multivariate models., Results: Data from 202 cases was included. 9 pre-hospital interventions were assessed. The incidence of endotracheal intubation and immobilisation of extremities was higher among patients in the PHAT-group compared to the ALS-only group (16.3% vs. 6.9%, p = 0.034) and (12.8% vs. 4.3%, p = 0.027) respectively. PHATs presence remained a significant predictor of these interventions also after taking confounding factors into account (OR 5.5, CL 1.5-19.7) and (OR 3.2 CI 1.0-9.8).PHAT was involved in a greater proportion of cases with <50.0% of survival (19.8% vs. 12.1%, p = 0.134). The average ISS was higher among cases receiving PHAT support in strata ISS 16-24 and ISS > 24 than cases in corresponding strata cared for by ALS teams alone (ISS 20.0 vs. 17.0, p = 0.048 and ISS 34.0 vs. 29.0, p = 0.019)., Conclusions: The incidence of endotracheal intubation and immobilization of extremities was greater among patients supported by PHAT, compared to patients cared for by ALS teams alone. This finding has to be interpreted in the light of a selection-bias where PHAT support was directed to more severely injured patients.

Background: The association between emergency department (ED) overcrowding and poor patient outcomes is well described, with recent work suggesting that the phenomenon causes delays in time-sensitive interventions, such as resuscitation. Even though most researchers agree on the fact that admitted patients boarding in the ED is a major contributing factor to ED overcrowding, little work explicitly addresses whether in-hospital occupancy is associated to the probability of patients being admitted from the ED. The objective of the present study is to investigate whether such an association exists., Methods: Retrospective analysis of data on all ED visits to Helsingborg General Hospital in southern Sweden between January 1, 2011, and December 31, 2012, was undertaken. The fraction of admitted patients was calculated separately for strata of in-hospital occupancy <95%, 95-100%, 100-105%, and >105%. Multivariate models were constructed in an attempt to take confounding factors, e.g., presenting complaints, age, referral status, triage priority, and sex into account. Subgroup analysis was performed for each specialty unit within the ED., Results: Overall, 118,668 visits were included. The total admitted fraction was 30.9%. For levels of in-hospital occupancy <95%, 95-100%, 100-105%, and >105% the admitted fractions were 31.5%, 30.9%, 29.9%, and 28.7%, respectively. After taking confounding factors into account, the odds ratio for admission were 0.88 (CI 0.84-0.93, P >0.001) for occupancy level 95-100%, 0.82 (CI 0.78-0.87, P >0.001) for occupancy level 100-105%, and 0.74 (CI 0.67-0.81, P >0.001) for occupancy level >105%, relative to the odds ratio for admission at occupancy level <95%. A similar pattern was observed upon subgroup analysis., Conclusions: In-hospital occupancy was significantly associated with a decreased odds ratio for admission in the study population. One interpretation is that patients who would benefit from inpatient care instead received suboptimal care in outpatient settings at times of high in-hospital occupancy. A second interpretation is that physicians admit patients who could be managed safely in the outpatient setting, in times of good in-hospital bed availability. Physicians thereby expose patients to healthcare-associated infections and other hazards, in addition to consuming resources better needed by others.

Background: Secondary hyperparathyroidism persists after renal transplantation in a substantial number of patients. Primary hyperparathyroidism and secondary hyperparathyroidism are both associated with abnormalities in glucose metabolism, such as insufficient insulin release and glucose intolerance. The association of hyperparathyroidism and diabetes after renal transplantation has, as far as we know, not been studied. Our aim was to investigate whether hyperparathyroidism is associated with new-onset diabetes mellitus after transplantation (NODAT) during the first year posttransplantation., Study Design: In a retrospective study, we analyzed data on patient characteristics, treatment details, and parathyroid hormone (PTH) in 245 adult nondiabetic patients who underwent renal transplantation between January 2000 and June 2011., Results: The first year cumulative incidence of NODAT was 15%. The first serum PTH value after transplantation was above normal range in 74% of the patients. In multiple logistic regression analysis, PTH levels above twice normal range (>13.80 pmol/L) were significantly associated with NODAT (odds ratio [OR], 4.25; 95% confidence interval [CI], 1.13-15.92; P = .03) compared with PTH within normal range (≤6.9 pmol/L). Age between 45 and 65 years (OR, 2.80; 95% CI, 1.07-7.36; P = .04) compared with age <45 years was also associated with NODAT., Conclusion: We found a strong association between hyperparathyroidism and NODAT in the first year after renal transplantation. Both conditions are common and have a negative impact on graft and patient survivals. Our results should be confirmed in prospective studies., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Multiple myeloma (MM) is at present an incurable malignancy, characterized by apoptosis-resistant tumor cells. Interferon (IFN) treatment sensitizes MM cells to Fas-induced apoptosis and is associated with an increased activation of Signal transducer and activator of transcription (Stat)1. The role of Stat1 in MM has not been elucidated, but Stat1 has in several studies been ascribed a pro-apoptotic role. Conversely, IL-6 induction of Stat3 is known to confer resistance to apoptosis in MM., Methods: To delineate the role of Stat1 in IFN mediated sensitization to apoptosis, sub-lines of the U-266-1970 MM cell line with a stable expression of the active mutant Stat1C were utilized. The influence of Stat1C constitutive transcriptional activation on endogenous Stat3 expression and activation, and the expression of apoptosis-related genes were analyzed. To determine whether Stat1 alone would be an important determinant in sensitizing MM cells to apoptosis, the U-266-1970-Stat1C cell line and control cells were exposed to high throughput compound screening (HTS)., Results: To explore the role of Stat1 in IFN mediated apoptosis sensitization of MM, we established sublines of the MM cell line U-266-1970 constitutively expressing the active mutant Stat1C. We found that constitutive nuclear localization and transcriptional activity of Stat1 was associated with an attenuation of IL-6-induced Stat3 activation and up-regulation of mRNA for the pro-apoptotic Bcl-2 protein family genes Harakiri, the short form of Mcl-1 and Noxa. However, Stat1 activation alone was not sufficient to sensitize cells to Fas-induced apoptosis. In a screening of > 3000 compounds including bortezomib, dexamethasone, etoposide, suberoylanilide hydroxamic acid (SAHA), geldanamycin (17-AAG), doxorubicin and thalidomide, we found that the drug response and IC50 in cells constitutively expressing active Stat1 was mainly unaltered., Conclusion: We conclude that Stat1 alters IL-6 induced Stat3 activity and the expression of pro-apoptotic genes. However, this shift alone is not sufficient to alter apoptosis sensitivity in MM cells, suggesting that Stat1 independent pathways are operative in IFN mediated apoptosis sensitization.

Background: Local tumour destruction has been shown to give rise to changes in immunocompetent cells. The aim of this study was to describe the effect of interstitial laser thermotherapy (ILT) of breast carcinoma in the tumour and in regional lymph nodes., Methods: Seventeen women that underwent radical surgical excision after non-radical ILT were studied. ILT was performed at a steady-state temperature of 48°C for 30 min. Surgical excision was performed 12 (6-23) days after ILT. Six patients with breast cancer not treated with ILT before surgery served as controls. Immunohistological reactions were performed on core needle biopsies prior to treatment and on the excised specimens., Results: ILT resulted in more CD8 lymphocytes and CD68 macrophages within the tumour (P < 0.05 and P < 0.01, respectively) and higher counts of CD20 (P < 0.05), CD68 (P < 0.001) and CD83 (P < 0.01) at the tumour border, when compared to pre-treatment values. In the control patients not receiving ILT, CD8 cells increased within the tumour after resection (P < 0.05). With the probable exception of CD25 Foxp3 cells, the presence of cancer in a lymph node influenced the findings in lymph nodes (examined for CD1a, CD25, Foxp3 CD25, CD83 cells). Thus, comparisons between ILT and control patients were restricted to patients without lymph node metastases. In these patients, ILT and resection were followed by a decrease in CD25 Foxp3 lymphocytes (P < 0.05), when compared to surgical resection alone., Conclusions: ILT induced changes in immunocompetent cells in patients with breast cancer. The stimulation of the immune system is an added feature of ILT in treatment of patients with breast cancer.

Background and Objective: Interstitial laser thermotherapy was used to treat rat liver tumours. The aim was to investigate the influence of temperature and temporary hepatic inflow occlusion on tumour growth and blood perfusion., Study Design/materials and Methods: Liver tumours were treated at 44°C at the tumour border for 30 minutes, hepatic inflow occlusion only, or a combination of these methods. Interstitial laser Doppler flowmetry was used to measure hepatic perfusion at the tumour border during and after heat treatment, for a total time of 60 minutes. Tumour growth was evaluated 6 days after treatment., Results: Tumours subjected to the combined treatment of hepatic inflow occlusion and interstitial laser thermotherapy displayed a blood perfusion reduction 30 minutes after treatment to 18 ± 5% of initial perfusion, which was significantly lower than achieved with thermotherapy alone (52 ± 10%, P = 0.02). The combined treatment and treatment with thermotherapy alone resulted in relative tumour growth of 0.3 ± 0.1 and 1.0 ± 0.2, respectively (P = 0.04)., Conclusion: Inflow occlusion enhanced the effect of thermotherapy not by augmenting treatment temperatures but by increasing the thermal sensitivity of the tumour, reflected by an immediate effect on tumour blood perfusion., (Copyright © 2011 Wiley-Liss, Inc.)

Aim: To find out if ILT can be used as radical treatment of breast cancer., Method: Twenty-four patients, aged 39-84 (mean 61), with invasive breast cancer were treated with ILT. All underwent mammography, ultrasound and core biopsy before treatment. The tumour was an invasive ductal carcinoma in 15 patients, a lobular carcinoma in eight and lobular-ductal cancer in one. Average tumour diameter was 14 mm on ultrasound (5-35). Patients were treated in the outpatient clinics under local anaesthesia. Probes were placed under ultrasound guidance, in 19 patients, and ILT was performed with a diode laser at a steady-state temperature of 48 degrees C for 30 min using temperature feedback control. Standard surgical excision was performed 12 (4-23) days after ILT and was preceded by Doppler ultrasound., Results: Treatment-induced necrosis of invasive cancer was 33% (range 0-100) and was complete in three patients. At follow-up before surgery, the extent of laser damage could not be judged with ultrasound, although abolished tumour blood flow was demonstrated after treatment resulting in large necroses. Efficacy of treatment varied negatively with tumour size. The inefficacy of ILT was mainly due to the underestimation of tumour size by mammography and ultrasound and the shortcomings of these methods to demonstrate tumour borders, tumour irregularity and carcinoma in situ (CIS). ILT was well tolerated. Five patients had breast tenderness, and three patients had pain, during the first day after treatment. Small skin necroses were observed in two patients., Conclusion: Small breast cancers can be treated radically with ILT. The method may become useful in the treatment of breast cancer but needs further refinement, even for small well-defined breast cancers, if it is going to be employed for radical treatment.

The aim of the present study was to explore hTERT as a target for IFN-induced sensitization to apoptosis in multiple myeloma (MM). IFN-alpha and IFN-gamma downregulated telomerase activity in the IL-6-dependent MM cell line U-266-1970. In MM cells undergoing IFN-induced sensitization to Fas-mediated apoptosis, the repression of telomerase was increased as compared to IFN-alpha treatment alone. Similar to the sensitization effect of IFN, the use of a dominant negative IkappaBalpha vector inhibiting hTERT activity via transcriptional targeting resulted in augmentation of Fas-mediated apoptosis. The mechanism underlying the reduction of telomerase activity by IFN was shown to be transcriptional repression of the hTERT gene. The present study does not support a direct effect of IFN on NF-kappaB binding to the hTERT promoter as underlying the transcriptional repression. We conclude that one potential mechanism whereby IFNs induce apoptosis sensitization is by repressing hTERT transcription and telomerase activity, thereby constituting attractive targets for MM therapy.

Previous studies in our laboratory have shown that interstitial laser thermotherapy (ILT) of an experimental liver tumour is superior to surgical excision, at least partly due to a laser-induced immunological effect. The aim of the present study was to investigate the time-response relationship of the ILT-induced immunisation and the cellular response of macrophages and lymphocytes. A dimethylhydrazine-induced adenocarcinoma was transplanted into the liver of syngeneic rats. Rats with tumour were treated 6-8 days later (tumour size 0.25-0.40 cm(3)) with ILT of tumour or resection of the tumour-bearing lobe. Two groups of rats without tumour were treated with resection of a normal liver lobe or ILT of normal liver. A challenging tumour was implanted into the liver of each rat 2, 5 or 10 weeks after primary treatment. Rats were killed 6, 12 and 48 days (or earlier due to their condition) after challenge (n = 8 in all groups). Immunohistochemical techniques were used to determine lymphocytes (CD8, CD4) and macrophages (ED1, ED2) in rats having had treatment of a primary tumour. Interstitial laser thermotherapy of the first tumour was followed by eradication of challenging tumour and absence of tumour spread. This contrasted with rapid growth and spread of challenging tumour in the other groups. In the challenging vital tumour tissue and in the interface between the tumour and surroundings, the number of ED1 macrophages and CD8 lymphocytes was higher in rats having been treated with the ILT of tumour than in those having undergone resection of the tumour-bearing lobe. The number of ED2 macrophages and CD4 lymphocytes was low and did not vary between these two groups. Interstitial laser thermotherapy elicited an immune response that eradicated a challenging tumour and was associated with increased numbers of tumour-infiltrating macrophages and CD8 lymphocytes.

Multiple myeloma (MM) is an as-yet incurable B-cell malignancy. Increased survival in vitro is a hallmark of MM cells, implying that a therapeutic potential may lie in circumventing antiapoptotic signals. We have previously reported that interferons (IFNs) sensitize MM cells to Fas/CD95-mediated apoptosis. In the present study, we explore the mechanism underlying this effect. In a wide screening of apoptosis-related genes, Apo2L/TRAIL (tumor necrosis factor [TNF]-related apoptosis inducing ligand) and Fas were identified as IFN targets. Sensitization to Fas-mediated apoptosis by IFNs was not affected by blocking Apo2L/TRAIL, suggesting that Apo2L/TRAIL is not a key mediator in this process. In contrast, we found that an elevated Fas expression was functionally linked to increased susceptibility to Fas-mediated apoptosis. This was further supported by the finding that IFN treatment enhanced Fas-mediated caspase-8 activation, one of the earliest signaling events downstream receptor activation. In addition, IFN treatment attenuated the interleukin 6 (IL-6)-dependent activation of signal transducer and activator of transcription 3 (Stat3), interfering with a known survival pathway in MM that has previously been linked with resistance to Fas-mediated apoptosis. Taken together, our results show that IFN-induced up-regulation of Fas sensitizes MM cells to Fas-mediated apoptosis and suggest that attenuation of Stat3 activation may be a potentially important event in this process.

Two scenarios for future pig meat production were constructed. The first was a "business as usual" scenario, where the pig feed was based on domestic grain and imported soy-meal, and no efforts were made to reduce pesticide use. The second scenario had a strong environmental focus, and both peas and rapeseed were grown at pig-farm level to produce grain and protein feed. Preventive measures, such as a more diverse crop rotation and mechanical weed control, were combined to reduce pesticide use. The two scenarios were environmentally assessed by Life Cycle Assessment (LCA) and a pesticide risk indicator model (PRI-Farm). The results showed environmentally sound possibilities to reduce pesticide dependency and risks by using altered plant protection strategies in pig-feed production. Organizing on-farm feed production so that protein feed crops are integrated with grain crops contributes to a more diverse crop rotation.

The heat shock proteins (HSPs) HSP70 and gp96 from necrotic tumour cells are considered to function as chaperones in presenting tumour antigens. We therefore studied HSP70 and immune cells in a transplantable carcinoma in the liver of rats after interstitial laser thermotherapy (ILT). Experiments were performed in Wistar FU rats using a dimethyl-hydrazine-induced adenocarcinoma implanted into the left lateral lobe of the liver. Rats were randomized to one of the following groups: a) ILT of tumour, b) sham ILT, or c) control. ILT was suboptimal and was performed at a steady-state temperature of 43 degrees C at the tumour margin for 30 minutes. Rats were killed 15 minutes, 5 hours, 10 hours, 15 hours or 12 days after treatment. Double immunohistochemistry was performed for HSP70 and ED1 macrophages or CD8 lymphocytes, and ELISA for serum concentrations of HSP70. After ILT, there was an increase of HSP70 immunoreactivity in tumours as compared to sham ILT. At the same time, tumour cells affected by ILT showed a shift of HSP70 from the cytoplasm to the nucleus with a peak at 10 hours. Few CD8-positive cells were found. There was an increase of tumour-infiltrating ED1 macrophages after ILT as compared to sham ILT at 10-15 hours after treatment. HSP70 was present in ED1 macrophages significantly more frequently after ILT than after sham ILT, and this was true both for HSP70 localized to the surface and the cytoplasm of the macrophage. There was a significant increase in serum HSP70 during the first 15 hours after ILT. In conclusion, laser thermotherapy resulted in increased HSP70 immunoreactivity within tumours and HSP70 shifts from cytoplasm to nucleus. Furthermore, it resulted in increased numbers of tumour-infiltrating macrophages and an increased presence of HSP70 in the membrane and cytoplasm of these macrophages.

Aim: The aim of this study was to investigate if Linomide affects growth and spread of a rat liver tumour when given alone and in combination with interstitial laser thermotherapy (ILT)., Materials and Methods: Experiments were performed in Wistar rats using a dimethyl-hydrazine-induced adenocarcinoma implanted into the left lateral lobe of the liver. The rats were randomised to one of the following groups: a) ILT and Linomide, b) ILT only, c) sham ILT, d) Linomide only, or e) control. ILT was intentionally suboptimal. Linomide (100 mg/kg/day) was given in the drinking water from the start of treatment for five days. ED1, ED2 macrophages and v Willebrand (factor VIII) were determined by an immunohistochemical technique., Results: Linomide reduced viable liver tumour volume both when it was given alone (p < 0.01) and when combined with ILT (p < 0.05), whereas it lowered intraperitoneal spread in ILT-treated rats alone. Six days after ILT, there was a reduction in the number of newly-recruited macrophages and blood vessels in the viable tumour tissue in rats receiving Linomide., Conclusion: Linomide reduced the growth of an adenocarcinoma transplanted into rat liver, when given alone or combined with laser thermotherapy and reduced the spread of tumour in laser-treated rats. The effects of Linomide in laser-treated rats appeared, at least in part, to be due to a reduction in newly-formed vessels, which might have been secondary to a reduced number of tumour-associated macrophages.

The aim of this study was to compare interstitial laser thermotherapy with excision of a liver tumour. A dimethylhydrazine-induced adenocarcinoma was implanted into the left lateral lobe of the rat liver, and treatment was performed 8 days later. Rats were treated with resection of the tumour-bearing lobe or underwent interstitial laser thermotherapy, which was performed at a steady-state temperature of 46°C for 30 min, 3 mm from the tumour margin. The incidence and extent of intraperitoneal spread was smaller after laser thermotherapy than after resection, with no difference in local control. Using inoculation of tumour cell suspensions into the lateral and the median lobes of the liver simultaneously and treating the lateral lobe tumour only, we found that laser thermotherapy reduced take and growth of the untreated tumour in the median lobe indicating that laser thermotherapy may induce immunologic effects. It is concluded that interstitial laser thermotherapy reduces spread of liver tumour as compared to resection. It is suggested that this can be at least partly explained by a laser-induced immunologic effect.

Objective: The purpose was to investigate whether normal ovarian surface epithelial cells, harvested from premenopausal and postmenopausal women, are capable of steroid production, and to evaluate effects of estradiol and progesterone on growth regulation of such cells., Methods: Ovarian surface epithelial cells were obtained by brushing of the ovarian surface of 9 premenopausal and 10 postmenopausal women undergoing surgery for benign gynecological diseases. The conditioned media after culture, with and without addition of FSH and LH, were analyzed for estradiol and progesterone. The proliferative effects of the steroids were analyzed using two different culture models, nonconfluent cells and confluent cells, and two different detection methods, [(3)H]thymidine incorporation and a colorimetric method assaying cell number., Results: The normal ovarian surface epithelial cells were found to secrete both estradiol and progesterone, a production that was not regulated by FSH or LH. Addition of steroids to the cultured cells did not induce any overall significant growth effects. However, progesterone significantly inhibited the growth of ovarian surface epithelial cells from three of the patients. Enhanced thymidine incorporation was observed in the presence of the progesterone receptor antagonist Org 31710 in the nonconfluent cultures of cells from postmenopausal women, but no effect of an estrogen receptor antagonist was observed., Conclusions: The normal ovarian surface epithelium is capable of steroid production, which is also often observed in tissue from ovarian epithelial tumors. Progesterone appeared to be a negative regulator of ovarian surface epithelial growth, while estradiol had no effect., (Copyright 2001 Academic Press.)

Background: In this study, electrochemotherapy (ECT), i.e. tumour treatment based on local augmentation of intracellular drug delivery from short, intense electric pulses, was evaluated in rats with an adenocarcinoma implanted into the liver. Tumour response and concentrations of macrophages and T-lymphocytes (CD4 and CD8) in and around the tumour were measured., Materials and Methods: Rats were treated with permeabilizing electric pulses, bleomycin, or both, eight days after implantation of the tumour, while one group received sham treatment., Results: Treatment with electric pulses and bleomycin resulted in a significantly reduced lesion volume and 92% cure rate (12 out of 13, p<0.0002 compared to the other treatment groups). The highest concentration of CD8 lymphocytes was found in tumours treated with electric pulses and bleomycin. Macrophages were found mainly in tumours treated with electric pulses, with or without bleomycin., Conclusion: Electrochemotherapy using millisecond exponential pulses and bleomycin is efficient in a rat liver tumour model and appears to stimulate the host's immune system.

A major diagnostic dilemma in the clinical gynaecological oncology setting is to preoperatively determine whether a complex ovarian mass is benign or malignant. The cell-cell adhesion molecule E-cadherin has previously been localised in biopsies from both benign and malignant epithelial ovarian tumours. In this study, soluble E-cadherin levels was measured with ELISA-technique in peripheral blood, ascites and cystic fluids from patients (n = 33) undergoing surgery for ovarian cystic masses. The levels of soluble E-cadherin were significantly higher in cystic fluid from cystadenocarcinomas (p < 0.001) and borderline tumours (p < 0.05) as compared to cystic fluid from cystadenomas. In ascites fluid and peripheral blood no significant differences were seen. However, ratios of cystic fluid/peripheral blood levels were significantly higher in cystadenocarcinoma (p < 0.001) and borderline tumours (p < 0.05) as compared to benign tumours. In conclusion, measurements of soluble E-cadherin in cystic fluid from patients presenting with complex ovarian masses may be beneficial in increasing the accuracy of preoperative diagnosis.

The purpose of this study was to evaluate the effects of FSH and LH on growth regulation of normal ovarian surface epithelial (OSE) cells harvested from both premenopausal and postmenopausal women. Ovarian surface epithelial cells were obtained through brushing of the ovarian surface during surgery. FSH and LH were added to the OSE cultures and the proliferative effects were analysed using two different culture models, non-confluent and confluent cells, and two different detection methods, [(3)H]thymidine incorporation and a colorimetric cell number assay. FSH lowered the OSE proliferation under non-confluent conditions (10-27%), and the inhibitory effect was most pronounced among cells from postmenopausal women (P: < 0.01). In the confluent model only cells from postmenopausal women showed significantly (P: < 0.05) decreased proliferation. No effects of LH on OSE cells were detected. The unexpected results of an anti-proliferative effect of FSH on OSE, and the absence of effect by LH, do not support the theory that gonadotrophins are directly involved in ovarian carcinogenesis through an enhanced proliferation of OSE cells.

Interleukin 8 (IL-8) is a chemotactic cytokine involved in the recruitment and activation of neutrophils as well as in cell proliferation and angiogenesis. Because these events are essential components of folliculogenesis, ovulation, and subsequent repair of the ruptured follicle, the presence and regulation of IL-8 in the human follicle of the menstrual cycle was investigated. The concentrations of IL-8 were higher in follicular fluids from dominant follicles of late follicular/ovulatory phase compared with those of midfollicular phase. IL-8 was detected in the media from cultured granulosa and theca cells, with 10-fold higher levels in the theca cell cultures. Exposure to FSH and LH increased the IL-8 secretion from granulosa cells, but no effect was seen in theca cell cultures. Estradiol and progesterone did not affect IL-8 secretion from any cell type. The cytokines IL-1alpha and IL-1beta, but not tumor necrosis factor alpha, enhanced IL-8 secretion from both cell types. IL-8 levels in cultures of granulosa-lutein cells from hyperstimulated in vitro fertilization cycles were not affected by either gonadotropins or steroids. These data provide evidence that ovarian IL-8 is gonadotropin and cytokine induced and may be involved in the hormonally regulated stages of follicular development and ovulation.

Background: The chemokine interleukin-8 is present in a variety of tumor types with suggested effects on proliferation, migration, and angiogenesis. Elevated levels of interleukin-8 are present in cyst fluids from malignant ovarian tumors. The origin and potential targets for this chemokine in ovarian tumors were investigated in this study., Methods: Interleukin-8 and its receptors were analyzed in 26 ovarian samples, including both normal and neoplastic tissue, with immunohistochemistry, Western blotting, and in situ hybridization., Results: The mRNA for IL-8 was detected in higher amounts in the epithelial compartments compared to stromal areas, while the IL-8 protein was present in both epithelial and stromal areas, and in cystic formations of the tumors. The tissue levels of IL-8 protein increased with lower differentiation of the tumors. Both types of IL-8 receptors were detected in most specimens. A typical expression pattern for IL-8 receptor A was detected, with expression only on the luminal side of the epithelial tumor cells, while IL-8 receptor B was more evenly distributed in the tissue., Conclusions: An increased synthesis of IL-8 during dedifferentiation of the tumor, and a typical expression pattern of the IL-8 receptor A were detected, indicating a function for IL-8 in biology of epithelial ovarian cancer.

Interstitial laser Doppler flowmetry was used to measure the effect of interstitial laser-induced thermotherapy on local blood perfusion in normal rat liver in the peripheral treatment region elevated to hyperthermic temperatures. The Nd:YAG laser emitting at 1064 nm was utilised as heat generation source. The plane-cut tip of an optical fibre was placed in the middle of the exteriorised left liver lobe. Blood perfusion and temperature were measured in the liver parenchyma 4 mm from the laser fibre. The temperature at the location of the liver temperature sensor was maintained at 41 or 44°C during 30 min by regulating the power of the heating laser. The laser Doppler signal was recorded during and after heat treatment, for a total time of 60 min. At 41°C, a significant increase in perfusion up to 1.3 times the initial value was observed 2-16 min after start of treatment. At 44°C, perfusion decreased continuously during and after treatment, and was significantly different from control 40 min after start of treatment. The results may be valuable in assessing the thermal response of tissues surrounding the target in interstitial laser-induced thermotherapy of liver tumours during conditions of normal blood flow.

The CCAAT/enhancer binding protein (C/EBP) family of transcription factors is involved in metabolism and differentiation of cells, especially in rodent liver cells and adipocytes. Their roles in vivo and in particular during pathophysiological conditions in humans are largely unknown. We have investigated the presence of C/EBPalpha, -beta, -delta and -zeta in normal ovaries and in epithelial ovarian tumours of different stages. Immunohistochemical experiments demonstrated that C/EBPalpha and C/EBPbeta were preferentially expressed in epithelial/tumour cells irrespective of stage or grade of the tumour. C/EBPbeta was located in the nuclei of the cells, in contrast to C/EBPalpha, which was present only in the cytoplasm of these cells. The nuclear localization of C/EBPbeta indicates an active role of this transcription factor in tumour cells, whereas the cytoplasmic distribution suggests a more passive function of C/EBPalpha. C/EBPdelta and -zeta demonstrated a more diverse distribution with predominant localization to epithelial cells, but stromal distribution was also noted. The intracellular distribution was confined to both the nucleus and the cytoplasm for C/EBPdelta and -zeta. Western blotting demonstrated that C/EBPalpha, -beta, -delta and -zeta were present in a majority of the samples. The amount of C/EBPbeta increased markedly with malignancy, i.e. with degree of dedifferentiation, while the other members of the C/EBP family displayed a more constant expression level. These results demonstrate an association between the expression of members of the C/EBP family and the formation of epithelial ovarian tumours, with C/EBPbeta as a potential marker for these tumours. As C/EBPbeta is known to be expressed during proliferation of cells in vitro, it may participate in the proliferative process of ovarian epithelial tumour cells in vivo and play a central role in tumour progression.

Due to the difficulties in separating malignant and benign ovarian cysts by transvaginal ultrasound and other techniques, there is a need for biochemical markers in serum or cyst fluids. In the present study we have evaluated the levels of the chemokine interleukin-8 (IL-8) in ovarian cysts. IL-8 is known to be expressed in the normal ovary and to influence proliferation and angiogenesis of several nonovarian types of tumors. Cyst fluids from benign (n = 15) and malignant (n = 13) ovarian tumors were analyzed. The levels of IL-8 were found to be significantly (13-fold) higher in cyst fluids from malignant tumors (18.1 +/- 7.5 ng/ml; mean +/- SE) compared to benign cysts (1.3 +/- 0.7 ng/ml). The plasma levels of IL-8 were considerably lower (2.9 and 0.3% of levels in benign and malignant cyst fluids, respectively) than in cyst fluids. No difference in the plasma levels of patients with benign or malignant tumor could be detected. In contrast, the levels of CA 125 were significantly higher in plasma of patients with malignant disease with the inverse relation in cyst fluids. In conclusion, the levels of IL-8 are markedly elevated in cyst fluid from malignant tumors compared to benign. This specific increase indicates a role for this cytokine in ovarian tumor biology., (Copyright 1998 Academic Press.)

The aim of this study was to compare interstitial laser thermotherapy with excision of a liver tumour. A dimethylhydrazine-induced adenocarcinoma was transplanted (implanted if not stated otherwise) into the left lateral lobe of the rat liver, and treatment was performed 8 days later. In the main experiment, rats were treated with resection of the tumour-bearing lobe or underwent interstitial laser thermotherapy, which was performed at a steady-state temperature of 46 degrees C for 30 min, 3 mm from the tumour margin. The incidence and extent of intraperitoneal spread was smaller after laser thermotherapy than after resection of the tumour-bearing lobe, with no difference in local control. Metastatic spread after resection of the median liver lobe was similar to that observed after sham procedures for thermotherapy or resection, suggesting that the advantage of thermotherapy was not due to a difference in surgical trauma. Additional studies showed that laser thermotherapy reduced intraperitoneal spread when treatment was suboptimal or in a tumour inoculation model and suggested that immunological mechanisms might be involved. It is concluded that interstitial laser thermotherapy reduces spread of liver tumour compared with resection.

Background and Objective: In this study a newly developed microprocessor controlled power regulation and thermometry system integrated with a diode laser (805 nm wavelength) was evaluated with respect to temperature distribution, effectiveness of regulation, and ability to predict temperature distributions by computer simulation., Study Design/materials and Methods: Experiments were performed in ground bovine muscle using either a single laser fiber or four-fibers. The target temperature at one (feedback) thermistor, placed 5 mm from one of the laser fibers, was set to 50 degrees C and was maintained by means of stepwise power regulation. The temperature distribution was monitored using multiple thermistor probes. A numerical model based on the bioheat equation was used to calculate the temperature distributions., Results: Temperature regulation was excellent with a tendency towards better regulation in the four-fiber than in the single-fiber experiments. Agreement between calculated and measured temperatures was good. The coagulated (> 55 degrees C) and hyperthermic (> 45 degrees C) volumes were 6 and 10-11 times larger, respectively, with four-fibers than with a single fiber., Conclusion: It is concluded that the stepwise power regulation system was efficient in maintaining a stable target temperature. The results indicate that the system can produce lesion volumes adequate for treating a relatively large tumor in a single session and that computer simulation may be useful for predicting temperature distribution.

Objective: To examine the effect of different temperatures and exposure times in interstitial laser thermotherapy., Design: Controlled laboratory study., Setting: University hospital, Sweden., Material: 48 male Wistar FU rats with dimethylhydrazine-induced adenocarcinoma transplanted into the liver., Intervention: Treatment was given with an Nd:YAG laser and a feedback system for temperature regulation. Light was delivered into the centre of the tumour and the feedback thermistor probe was placed 3 mm from the tumour margin. Rats were treated at steady-state temperatures at the feedback thermistor of 43, 46, or 50 degrees C for 30 minutes, and at a steady-state temperature of 46 degrees C at the feedback thermistor also for 10 and 20 minutes., Main Outcome Measurement: Tumour control as assessed 6 days after treatment using light microscopical examination including immunohistochemical determination of bromodeoxyuridine (BrdU) incorporation into DNA as a measure of cell viability., Results: Complete tumour necrosis was achieved in all rats treated for 30 minutes, in 6/8 rats treated for 10 minutes and in 6/8 rats treated for 20 minutes at 46 degrees C. During steady-state thermotherapy, temperatures at the tumour margin were about 11 degrees higher than at the feedback thermistor (range 54-61 degrees C). The surrounding liver tissue also became necrotic so that the total necrosis volume exceeded the pretreatment tumour volume., Conclusion: Interstitial laser thermotherapy at temperatures ranging from 54-61 degrees C at the tumour margin ensures total necrosis of a transplanted rat liver carcinoma provided that treatment is given for 30 minutes.

Background/aims: The aim was to investigate the effect of blood inflow occlusion on lesion size and ultrasonographic findings during interstitial laser thermotherapy of normal liver., Methodology: Pigs were treated with or without hepatic inflow occlusion at a laser power of 3W or without inflow occlusion at 5 W (target temperature 43 degrees C). The thermotherapy system consisted of an Nd:YAG laser and a temperature feedback circuit. Ultrasonography was performed immediately after treatment. Lesion size was determined using light microscopy including immunohistochemistry with bromodeoxyuridine., Results: Hyperechoic ultrasonographic changes were observed after treatment with inflow occlusion or when there was carbonization. If carbonization did not occur, unoccluded blood flow was associated with hypoechoic lesions. Following inflow occlusion, maximum lesion width 2 and 6 days after thermotherapy averaged 21.9 +/- 1.3 and 20.2 +/- 0.8 (means +/- SEM) mm, respectively. This was larger than the corresponding values of 10.8 +/- 0.8 and 11.1 +/- 2.0 observed after treatment without inflow occlusion at 3W (p < 0.01). Increase in laser power from 3 to 5W in experiments without inflow occlusion produced early carbonization and a slight increase in lesion size that did not match that produced by inflow occlusion. Ultrasound gave a correct prediction of necrosis size after treatment with inflow occlusion but overestimated the necrosis when inflow occlusion was not used. Ultrasound was furthermore unable to predict size of necrosis in individual experiments., Conclusion: Blood flow has a major influence on lesion size in interstitial laser thermotherapy of the liver and affects ultrasonographic images. Also, it appears that intraoperative ultrasonography cannot monitor lesion size with an accuracy that is sufficient for clinical use.

Transient hepatic arterial occlusion causes necrosis in solid hepatic tumors in the rat, but regrowth of tumor cells and capillaries takes place from the tumor periphery. It was therefore considered of interest to combine this treatment with the angiogenesis inhibitor TNP-470 (therapeutic model). Wistar rats with a dimethylhydrazine-induced adenocarcinoma implanted into the liver received one of the following treatments: TNP-470 + transient hepatic ischemia, transient hepatic ischemia alone, TNP-470 alone or sham solution alone. Rats were sacrificed one week after the start of treatment. In addition, we investigated if TNP-470 decreases the risk of tumor take in the liver after intraportal injection of viable tumor cells (adjuvant study). Transient hepatic ischemia combined with TNP-470 gave a smaller increase in tumor volume than transient hepatic ischemia (p < 0.01), TNP-470 (p < 0.001) alone or no treatment (p < 0.001). Transient hepatic ischemia or TNP-470 caused a significant suppression of tumor growth when compared to controls (p < 0.01 in both cases). In the adjuvant study, TNP-470 caused retardation of tumor growth (p < 0.01 as compared to controls) but did not affect tumor number. It is concluded that TNP-470 suppressed tumor growth, both alone and in combination with transient hepatic ischemia, but did not affect take of tumor.

The ovarian surface epithelium (OSE) is the origin of the majority of human ovarian cancers. These adenocarcinomas are characterized by initial local growth followed by spreading into the peritoneal cavity at later stages of tumor progression. The cell-adhesion molecule E-cadherin (E-cad) plays an important role in maintaining tissue integrity. Disappearance or impaired function of E-cad have often been associated with tumor formation and invasion in vivo and in vitro. The cell-specific expression of E-cad was investigated in normal human ovaries (n = 12), in benign (n = 5) and borderline (n = 4) ovarian epithelial tumors and in adenocarcinomas of different stages and histological grades (n = 18), by immunohistochemistry and immunoblotting. An ovarian cancer cell line (NIH-OVCAR3) was used as a reference. The epithelial origin of the cells was confirmed with cytokeratin (AE1/AE3) staining. In normal ovaries, the expression of E-cad was limited to inclusion cysts or deep clefts lined with OSE, whereas no staining of the OSE could be demonstrated at the surface of the ovary. In contrast, benign and borderline tumors uniformly expressed E-cad. This was observed in malignant tumors of all stages despite their degree of differentiation. E-cad was also present in metastasis from such tumors. The cell-specific expression of E-cad in inclusion cysts of normal ovaries and in epithelial layers of borderline tumors indicates a role for E-cad in the early events of the progression to a malignant phenotype. E-cad was not downregulated in later stages of ovarian cancer progression.

A new index of orthodontic treatment need was introduced in Norway in 1990. On a morphologic and functional basis the four groups very great (A), great (B), obvious (C) and little/no (D) need were defined for social insurance refunding. The purpose of the present study was to investigate to what extent the new index corresponded with orthodontic concern among potential orthodontic patients and their parents. Of 104 randomly selected fourth grade children, 99 (48 girls, 51 boys, mean age 10.7 yr) presented themselves for clinical examination and interview. One parent was asked to accompany the child, and 93 parents attended. On the basis of clinical examination, morphologic measurements on study casts, and X-rays, the children were allocated to one of the four groups defined by the index. In separate questionnaires the children and the parents were asked to assess satisfaction with own/child's dental arrangement and desire for orthodontic treatment. The interview data were transformed into a composite measure representing orthodontic concern. The results indicated that orthodontic concern was significantly related to index group. For the individuals who expressed concern the new index seemed to be meaningful for allocation of public subsidies, as most individuals (85%) who expressed concern exhibited malocclusions fulfilling the criteria for receiving public subsidies of treatment costs. However, more than 50% of the individuals allocated to group B (great need) did not experience a need for treatment.