Effects of short-day treatment on long-term growth performance and maturation of farmed Arctic charr Salvelinus alpinus reared in brackish water.

The effects of a 6 week short-day photoperiod followed by continuous light, applied during the juvenile phase of Arctic charr Salvelinus alpinus in fresh water on smoltification and on the long-term growth and maturity following transfer to brackish water (BW) (constant salinity of either 17 and 27 or increasing salinity in steps from 17 to 27) were investigated. Prior to salinity transfer, the juveniles were either reared at continuous light (C group) or reared for 6 weeks on a short day (8L:16D, S group) followed by continuous light (24L:0D). Increased salinity had negative effect on growth, with female fish reared at 17 salinity weighing 19 and 27% more than the salinity-step group (17-27) and the 27 salinity group, respectively. The stepwise acclimation to salinity had limited advantage in terms of growth rate. Short photoperiod for 6 weeks (November to January) followed by continuous light improved growth, but not seawater (SW) tolerance. Gill Na(+) , K(+) -ATPase activity and plasma Na(+) levels changed with time, indicating some variation in osmoregulatory capacity during the experimental period. Overall, there appear to be interactive effects on maturation from applying short-day photoperiod followed by rearing at higher salinities. Plasma leptin varied with time and may be linked to stress caused by the observed variations in osmoregulatory ability. It is concluded that changes in growth rates observed in this study are mainly related to rearing salinity with higher growth rates at lower salinities. Short-day photoperiod has some growth-inducing effects but did not improve SW tolerance. Farmers of S. alpinus using BW for land-based rearing should keep salinity at moderate and stable levels according to these results to obtain best growth.

Long-term rearing of Arctic charr Salvelinus alpinus under different salinity regimes at constant temperature.

Arctic charr Salvelinus alpinus of the Hólar strain (mean ± s.e. body mass = 152·1 ± 3·1 g) were reared at four different salinity regimes at a constant temperature of 7·4° C. Two groups were given a three-month acclimation in salinity 18 before the salinity was increased to either 25 or 29 (groups called A25 and A29), and two groups were reared in salinities 25 or 29 over the full experimental period of 409 days (groups called F25 and F29). In the first 3 months, the A25 and A29 groups had the highest growth rates. By October 2011, there were no significant differences (two-way nested ANOVA, P > 0·05) in the mean body masses among A25, F25 and F29 (c. 1450 g), whereas A29 had a lower mean mass (1282 g). The growth in the last period from October 2011 to January 2012 was reduced by sexual maturation in the highest salinity regimes (A29 and F29), whereas fish in groups A25 and F25 showed high growth throughout the study. Males in all salinity groups had higher growth rates than females for the most part of the study, but the divergence between the sexes was most pronounced in the highest salinity regimes. All salinity groups showed distinct changes in Na(+) , K(+) -ATPase activity, with high activity in spring and summer, and lower activity in the autumn. Plasma sodium (Na(+) ) levels were stable indicating that none of the experimental groups had problems in maintaining hydromineral balance during the study. While plasma leptin levels were not affected by salinity regimes, it was noted that these levels were 13-30% higher in fish with empty guts compared with those having food in their gut at the time of sampling. This suggests a link between leptin levels and food intake, indicating that this hormone may play a role in food intake and energy allocation in fishes.

Smoking is a risk factor for recurrence of intestinal stricture after endoscopic dilation in Crohn's disease.

BACKGROUND: Endoscopic balloon dilation is an efficacious and safe alternative to surgery as treatment of short intestinal strictures in Crohn's disease (CD). Factors predicting outcome of the procedure are not well described. AIM: To evaluate whether smoking at diagnosis, treatment with azathioprine, or other clinical variables may affect clinical outcome after endoscopic dilation. The endpoint was requirement of a new intervention such as dilation or surgery with intestinal resection or strictureplasty. METHODS: Retrospective study of 83 patients with CD who underwent endoscopic balloon dilation of an intestinal stricture between 1987 and 2009. RESULTS: After index dilation 55/83 patients underwent a new intervention. Among current smokers, 31/32 (97%) underwent another intervention compared to 18/33 (55%) among never smokers (adjusted HR: 2.50, 95% CI: 1.14-5.50, P = 0.022). After 5 years, cumulative probability of new intervention was 0.81 in smokers compared to 0.52 in never smokers; difference 0.29 (95% CI: 0.07-0.52, P = 0.01). In 16 patients, therapy with azathioprine was initiated before or shortly after the index dilation; 7/16 underwent a new intervention compared to 48/67 of those without azathioprine (HR: 0.46, 95% CI: 0.21-1.03, P = 0.06). After adjustment for other variables, the association was even weaker (HR: 0.80, 95% CI: 0.29-2.18, P = 0.668). Sex, age at diagnosis, age at first dilation, balloon size, location of stricture, and treatment period did not influence outcome. CONCLUSIONS: Smoking doubles the risk of recurrent stricture formation requiring a new intervention after index dilation. Maintenance therapy with azathioprine did not influence the subsequent course and need for a new intervention.

Pharmaceutical treatment patterns for patients with a diagnosis related to chronic pain initiating a slow-release strong opioid treatment in Sweden.

Slow-release strong opioids (SRSO) are indicated in patients with severe chronic pain. Side effects, lack of efficacy and risk of dependency limit their use in clinical practice. The aim of this study was to explore prescription patterns of SRSO in Swedish real-world data on patients with a diagnosis related to chronic pain (DRCP). Patient-level data were extracted from the national prescriptions register and a regional register with diagnosis codes. The prescription sequences, switches, co-medications, and strengths over time were analyzed for cancer and noncancer patients. Of 840,000 patients with a DRCP, 16,257 initiated treatment with an SRSO in 2007 to 2008. They were 71 years old on average; 60% were female and 34% had cancer. The most common first prescription was oxycodone (54%) followed by fentanyl (19%), buprenorphine (14%), and morphine (13%). 63% refilled their prescription within 6 months, and 12% switched to another SRSO, most commonly fentanyl. After 3 years, 51% of cancer and 27% of noncancer patients still being in contact with health care remained on any SRSO. Of noncancer patients, 35% had a psychiatric co-medication (SSRI or benzodiazepine). In conclusion, fewer patients remain on SRSO in the long-term in clinical practice than reported in previous clinical trials. Oxycodone is the most common first SRSO prescription and one-third of patients get a prescription indicating psychiatric comorbidity. Our interpretation of these findings are that there is need for better treatment options for these patients, and that more effort is needed to improve treatment guidelines and to ascertain that these guidelines are followed.

Endoscopic dilation is an efficacious and safe treatment of intestinal strictures in Crohn's disease.

BACKGROUND: Bowel strictures are a major cause of morbidity, hospitalisation and surgery in Crohn's disease. AIM: We report short- and long-term efficacy and safety of endoscopic balloon dilation of strictures due to Crohn's disease. METHODS: Retrospective study of patients who underwent endoscopic balloon dilation between 1987 and 2009. RESULTS: We performed 776 dilations, of which 621 (80%) were on anastomotic strictures, in 178 patients (94 women) with Crohn's disease. At first dilation, median (IQR) age of patients was 45 (37-56) years and disease duration 16 (8-22) years. Technical success rate was 689/776 (89%). A subset of 75 patients from the primary catchment area, with >5-year follow-up, underwent a total of 246 dilations. At 1-year follow-up, 60/75 (80%) patients had undergone no further intervention or one additional dilation only. At 3 and 5 years, corresponding figures were 43/75 (57%) and 39/75 (52%). Cumulative proportions of patients undergoing surgery at 1, 3 and 5 years were 13%, 28% and 36%. Complication rate per procedure for all 178 patients was 41/776 (5.3%), bowel perforation (n = 11, 1.4%), major bleeding requiring blood transfusion (n = 8, 1.0%), minor bleeding (n = 10, 1.3%) and abdominal pain or fever (n = 12, 1.5%). Ten patients underwent surgery due to complications (perforation n = 8, bleeding n = 2). There was no procedure-related mortality. CONCLUSIONS: Endoscopic balloon dilation is an efficacious and safe alternative to surgical resection of intestinal strictures in Crohn's disease. At 5-year follow-up, 52% of patients required no further or one additional dilation only, whereas 36% had undergone surgical resection. Complication frequency was low.

Socio-economic burden of patients with a diagnosis related to chronic pain--register data of 840,000 Swedish patients.

BACKGROUND: Chronic pain constitutes a substantial socio-economic challenge but little is known about its actual cost. AIM: To estimate the direct and indirect costs of patients with a diagnosis related to chronic pain (DRCP), to determine variation in these costs across different diagnosis groups, and to identify what resources constitute the most important components of costs. METHODS: Patient level data from three administrative registries in Västra Götalandsregionen in Sweden including inpatient and outpatient care, prescriptions, long-term sick-leaves, and early retirement were extracted. Patients with a DRCP between January 2004 and November 2009 were selected. RESULTS: In total, 840,000 patients with a DRCP were identified. The mean total costs per patient and year were estimated at 6400 EUR but were higher for patients with cancer (10,400 EUR). Patients on analgesic drugs had more than twice as high costs as patients without analgesic drugs, on average. Indirect costs (sick-leaves and early retirement) constituted the largest cost component (59%) followed by outpatient (21%) and inpatient care (14%), whereas analgesic drug prescriptions constituted less than 1 percent of the total. CONCLUSIONS: The socio-economic burden of patients with a diagnosis related to chronic pain amounts to 32 billion EUR per year, when findings from Västra Götalandsregionen are extrapolated to the whole of Sweden. This compares to a fifth of the total Swedish tax burden in 2007 or about a tenth of Swedish GDP. This study does not provide evidence on what costs are caused by chronic pain per se. However, the higher costs of patients on analgesic drugs might indicate that the consequences of pain are of major importance.

The economic cost of brain disorders in Europe.

BACKGROUND AND PURPOSE: In 2005, we presented for the first time overall estimates of annual costs for brain disorders (mental and neurologic disorders) in Europe. This new report presents updated, more accurate, and comprehensive 2010 estimates for 30 European countries. METHODS: One-year prevalence and annual cost per person of 19 major groups of disorders are based on 'best estimates' derived from systematic literature reviews by panels of experts in epidemiology and health economics. Our cost estimation model was populated with national statistics from Eurostat to adjust to 2010 values, converting all local currencies to Euros (€), imputing cost for countries where no data were available, and aggregating country estimates to purchasing power parity-adjusted estimates of the total cost of brain disorders in Europe in 2010. RESULTS: Total European 2010 cost of brain disorders was €798 billion, of which direct health care cost 37%, direct non-medical cost 23%, and indirect cost 40%. Average cost per inhabitant was €5.550. The European average cost per person with a disorder of the brain ranged between €285 for headache and €30 000 for neuromuscular disorders. Total annual cost per disorder (in billion € 2010) was as follows: addiction 65.7; anxiety disorders 74.4; brain tumor 5.2; child/adolescent disorders 21.3; dementia 105.2; eating disorders 0.8; epilepsy 13.8; headache 43.5; mental retardation 43.3; mood disorders 113.4; multiple sclerosis 14.6; neuromuscular disorders 7.7; Parkinson's disease 13.9; personality disorders 27.3; psychotic disorders 93.9; sleep disorders 35.4; somatoform disorder 21.2; stroke 64.1; and traumatic brain injury 33.0. CONCLUSION: Our cost model revealed that brain disorders overall are much more costly than previously estimated constituting a major health economic challenge for Europe. Our estimate should be regarded as conservative because many disorders or cost items could not be included because of lack of data.

The epidemiology and clinical features of portal vein thrombosis: a multicentre study.

BACKGROUND: Reliable epidemiological data for portal vein thrombosis are lacking. AIMS: To investigate the incidence, prevalence and survival rates for patients with portal vein thrombosis. METHODS: Retrospective multicentre study of all patients registered with the diagnosis of portal vein thrombosis between 1995 and 2004. RESULTS: A total of 173 patients (median age 57 years, 93 men) with portal vein thrombosis were identified and followed up for a median of 2.5 years (range 0-9.7). The mean age-standardized incidence and prevalence rates were 0.7 per 100,000 per year and 3.7 per 100,000 inhabitants, respectively. Liver disease was present in 70 patients (40%), malignancy in 27%, thrombophilic factors in 22% and myeloproliferative disorders in 11%. Two or more risk factors were identified in 80 patients (46%). At diagnosis, 65% were put on anticoagulant therapy. Thrombolysis, TIPS, surgical shunting and liver transplantation were performed in 6, 3, 2 and 8 patients, respectively. The overall survival at 1 year and 5 years was 69% and 54%. In the absence of malignancy and cirrhosis, the survival was 92% and 76%, respectively. CONCLUSIONS: The incidence and prevalence rates of portal vein thrombosis were 0.7 per 100,000 inhabitants per year and 3.7 per 100,000 inhabitants, respectively. Concurrent prothrombotic risk factors are common. The prognosis is variable and highly dependent on underlying disease.

Clinical trial: colectomy after rescue therapy in ulcerative colitis - 3-year follow-up of the Swedish-Danish controlled infliximab study.

BACKGROUND: The long-term efficacy of infliximab as rescue therapy in steroid-refractory ulcerative colitis is not well described. AIM: To examine the long-term efficacy of infliximab as a rescue therapy through a 3-year follow-up of a previous placebo-controlled trial of infliximab in acute steroid-refractory ulcerative colitis. METHOD: In the original study, 45 patients were randomized to a single infusion of infliximab 5 mg/kg or placebo, and at 3 months, 7/24 patients given infliximab were operated vs. 14/21 patients given placebo. Three years or later, patients were asked to participate in a clinical follow-up. RESULTS: Another seven patients underwent colectomy during follow-up: five in the infliximab group and two in the placebo group. After 3 years, a total of 12/24 (50%) patients given infliximab and 16/21 (76%) given placebo (P = 0.012) had a colectomy. None of eight patients in endoscopic remission at 3 months later had a colectomy compared with 7/14 (50%) patients who were not in remission (P=0.02). There was no mortality. CONCLUSION: The benefit of rescue therapy with infliximab in steroid-refractory acute ulcerative colitis remained after 3 years. The main advantage of infliximab treatment occurred during the first 3 months, whereas subsequent colectomy rates were similar in the two groups. Mucosal healing at 3 months influenced later risk of colectomy.

A prospective study on antibody response to repeated vaccinations with pneumococcal capsular polysaccharide in splenectomized individuals with special reference to Hodgkin's lymphoma.

BACKGROUND: Splenectomy is accompanied by a life-long risk of overwhelming postsplenectomy infection (OPSI), mainly caused by polysaccharide (PS) encapsulated bacteria such as Streptococcus pneumoniae. Despite extensive prophylactic efforts the mortality and morbidity rates remain high. The present study was based on a strategy with a predefined vaccination algorithm including repeated 23-valent pneumococcal vaccinations and monitoring of pneumococcal antibody levels. The antibody levels of splenectomized Hodgkin's lymphoma (HL) patients were compared with those patients splenectomized due to immune-mediated cytopenias [autoimmune haemolytic anaemia (AIHA) and immune thrombocytopenic purpura (ITP)] and also individuals who were splenectomized because of trauma (TRAUMA). METHODS: A total of 311 splenectomized individuals were included in this prospective study (208 HL; 15 AIHA; 60 ITP; 28 TRAUMA). Depending on their individual anti-PS antibody levels measured by enzyme-linked immunosorbent assay technique the patients were revaccinated with 23-valent pneumococcal PS vaccine up to four times in accordance with the predefined algorithm. For each vaccination occasion, serum was collected at vaccination, after 1 month +/- 2 weeks (peak), and after 1 year +/- 6 months (follow-up). Patient files, a national population-based database, and microbiological databases were checked for 124 HL patients to identify OPSI. RESULTS: A significant response was recorded on primary vaccination as well as on two revaccination occasions for HL, AIHA/ITP, as well as TRAUMA patients. None of the variables age, gender, or time elapsed between splenectomy and first pneumococcal vaccination was found to be associated with mean PS antibody levels at prevaccination, peak or follow-up. No severe adverse events were reported. Amongst 124 clinically monitored HL patients, 10 OPSI were recorded in seven patients during the study period. One of these patients, a middle-aged female, died as a result of fulminant pneumococcal bacteraemia, which was her third OPSI during a 7-year period. CONCLUSIONS: A significant response to pneumococcal PS vaccination was found in all three groups (HL, AIHA/ITP and TRAUMA) of splenectomized patients. Importantly, both primary and repeated vaccinations were safe. Until further knowledge is gained regarding the protective concentration of serotype-specific antibody concentrations we believe that the value of vaccination and frequent revaccination (every 1-5 years) in combination with education of patients and health care professionals and clinical monitoring is beneficial for these patients at risk for OPSI.

Environmental tobacco smoke and myocardial infarction among never-smokers in the Stockholm Heart Epidemiology Program (SHEEP).

An increased risk for myocardial infarction (MI) related to environmental tobacco smoke (ETS) exposure has previously been reported, but several aspects of the association are still uncertain. We studied the MI risk associated with ETS exposure among 334 nonfatal never-smoking MI cases and 677 population controls, 45-70 years of age, in Stockholm County. A postal questionnaire with a telephone follow-up provided information on ETS exposure and other potential risk factors for MI. After adjustment for age, gender, hospital catchment area, body mass index, socioeconomic status, job strain, hypertension, diet, and diabetes mellitus, the odds ratio for MI was 1.58 (95% confidence interval = 0.97-2.56) for an average daily exposure of 20 cigarettes or more from the spouse. Combined exposure from spouse and work showed an increasing odds ratio for MI, up to 1.55 (95% confidence interval = 1.02-2.34) in the highest category of weighted duration, that is, more than 90 "hour-years" of exposure (1 "hour-year" = 365 hours, or 1 hour per day for 1 year). In addition, more recent exposure appeared to convey a higher risk. Our data confirm an increased risk of MI from exposure to ETS and suggest that intensity of spousal exposure, combined exposure from spouse and work, and time since last exposure are important.

Enhanced in vitro production of amyloid-like fibrils from mutant (S20G) islet amyloid polypeptide.

UNLABELLED: Islet amyloid polypeptide (IAPP, "amylin") is the amyloid-fibril-forming polypeptide in the islets of Langerhans associated with type 2 diabetes mellitus. A missense mutation in the IAPP gene associated with early-onset type 2 diabetes has been identified in the Japanese population. This mutation results in a glycine for serine substitution at position 20 of the mature IAPP molecule. Whether or not formation of islet amyloid with resulting destruction of islet tissue is the cause of this diabetes is yet not known. The present in vitro study was performed in order to investigate any influence of the amino acid substitution on the fibril formation capacity. Synthetic full-length wild type (IAPPwt) and mutant (IAPPS20G) as well as corresponding truncated peptides (position 18-29) were dissolved in dimethylsulfoxide (DMSO) or in 10% acetic acid at a concentration of 10 mg/mL and their fibril forming capacity was checked by Congo red staining, electron microscopy, a Congo red affinity assay and Thioflavine Tfluorometric assay. It was found that full-length and truncated IAPPS20G both formed more amyloid-like fibrils and did this faster compared to IAPPwt. The fibril morphology differed slightly between the preparations. CONCLUSION: The amino acid substitution (S20G) is situated close to the region of the IAPP molecule implicated in the IAPP fibrillogenesis. The significantly increased formation of amyloid-like fibrils by IAPPS20G is highly interesting and may be associated with an increased islet amyloid formation in vivo and of fundamental importance in the pathogenesis of this specific form of diabetes.

Radiation-associated sarcomas are characterized by complex karyotypes with frequent rearrangements of chromosome arm 3p.

Ionizing radiation is a well-known risk factor for sarcoma development. To investigate whether radiation-associated sarcomas are characterized by chromosome aberrations that distinguish them from de novo sarcomas, we identified those patients in our series of more than 500 cytogenetically abnormal sarcomas that fulfilled the following criteria: (1) each patient should have been irradiated for another malignancy at least 3 years prior to the sarcoma diagnosis, and (2) the sarcoma should have developed within the field of radiation. Ten patients fulfilling these criteria could be retrieved (median age at sarcoma diagnosis was 55 years, range 17-79; median latency period between primary tumor and radiation-associated sarcoma was 9 years, range 4-30). The diagnoses were typical for radiation-associated sarcomas: 2 each of malignant fibrous histiocytoma, leiomyosarcoma, and pleomorphic sarcoma, and 1 each of osteosarcoma, fibrosarcoma, myxofibrosarcoma, and spindle cell sarcoma. All 10 cases had relatively complex karyotypes with multiple, mostly unbalanced, structural rearrangements, similar to what has been reported in de novo sarcomas of the corresponding histologic subtypes. The only cytogenetic features that were unusually frequent among the radiation-associated sarcomas were the finding of unrelated clones in 3 cases, and loss of material from chromosome arm 3p, in particular 3p21-3pter, in 8 cases. Loss of the same chromosome segment has been described in 4 of the 8 previously published cases of radiation-associated sarcomas that have been analyzed after short-term culturing, which makes this imbalance significantly (P < 0.001) more frequent among radiation-associated sarcomas (12 of 18 cases) than among unselected cases of the corresponding histologic subtypes (74 of 282 cases). In contrast to the cytogenetic results, no 3p deletions were detected among the 6 cases of the present series that could be analyzed by comparative genomic hybridization (CGH). The most frequent imbalance detected by CGH was gain of 15cen-q15 (3 cases), followed by loss of chromosome 13 and gain of 5p, and 7cen-q22, each detected in 2 cases.

Treatment outcome in patients younger than 60 years with advanced stages (IIB-IV) of Hodgkin's disease: the Swedish National Health Care Programme experience.

BACKGROUND: Despite improved treatment results achieved in Hodgkin's disease (HD), only about 70% of patients with advanced stages are cured. The primary aim of this study was to evaluate the outcome of advanced stages (IIB-IVB) of HD in younger patients in an unselected population-based group of patients. The patients were recommended individualized treatment with respect to number of chemotherapy (CT) courses and post-CT radiotherapy (RT) based on pretreatment characteristics and tumour response. Secondly, we investigated if variables of prognostic importance could be detected. PATIENTS AND METHODS: Between 1985-92, 307 patients between 17-59 yr of age (median 36) were diagnosed with HD in stages IIB-IVB in 5/6 health care regions in Sweden. Median follow-up time was 7.8 yr (1.3-13). Retrospectively, laboratory parameters were collected. RESULTS: In total, 267 (87%) patients had a complete response (CR). The overall and disease-free 10-yr survivals in the whole cohort were 76% and 67%, respectively. There was no difference in survival between the groups of patients who received 6 or 8 cycles of CT. Survival was not higher for patients in CR after CT when RT was added. For those in PR after CT, additional RT raised the frequencies of CR. A selected group of pathologically staged patients was successfully treated with a short course (2 cycles) of CT + RT. In univariate analyses survival was affected by age, stage IVB, bone-marrow involvement, B-symptoms, S-LDH, S-Alb and reaching CR or not after 2, 4 and 6 cycles of CT. In a multivariate analysis, age and reaching CR after 6 cycles of CT remained statistically significant. CONCLUSIONS: The lack of difference in survival between the groups of patients who received 6 versus 8 cycles of CT indicates a successful selection of patients for the shorter treatment. Reaching a rapid CR significantly affected outcome. Whether some patients need less CT than the generally recommended 8 courses can properly only be evaluated in a randomised study. Additional RT may play a role in successful outcome, particularly if residual tumours are present, but its precise role can also only be defined in prospectively randomised studies. Reaching CR after CT was the most important variable affecting survival besides age.

YopH dephosphorylates Cas and Fyn-binding protein in macrophages.

The tyrosine phosphatase YopH is an essential virulence effector of pathogenic Yersinia spp. YopH, which is translocated from extracellularly located bacteria into interacting target cells, blocks phagocytosis by professional phagocytes. We show here that immunoprecipitation of YopH from lysates of J774 cells infected with Y. pseudotuberculosis expressing an inactive form of YopH resulted in co-precipitation of certain phosphotyrosine proteins. The association between the inactive YopH and phosphotyrosine proteins in the 120 kDa range was rapid and could be detected after 2 min of infection. The proteins were identified as the docking proteins Cas and Fyn-binding protein (FYB). Upon infection of J774 cells with Y. pseudotuberculosis lacking YopH expression both of these proteins became tyrosine phosphorylated. Moreover, this infection caused recruitment of Cas to peripheral focal complexes, and FYB was relocalized to areas surrounding these structures. Both Cas and FYB became dephosphorylated upon infection with Y. pseudotuberculosis expressing active YopH, and this was associated with disruption of focal complexes. With regard to the previous identification of Cas and focal complexes as targets of YopH in HeLa cells, the present study supports an important role for these targets in a general mechanism of bacterial uptake.

No serious late cardiac effects after adjuvant radiotherapy following mastectomy in premenopausal women with early breast cancer.

PURPOSE: To assess cardiac mortality, coronary artery disease, myocardial dysfunction, and valvular heart disease in women younger than 65 years of age, at least 10 years after adjuvant radiotherapy following mastectomy in early breast cancer. METHODS AND MATERIALS: Ninety women (45-64 years old) with Stage II breast cancer without relapse, included in the South Sweden Breast Cancer Trial (premenopausal arm), with or without adjuvant postoperative radiotherapy +/- cyclophosphamide were examined with myocardial scintigraphy and echocardiography/Doppler, 10-17 years after radiotherapy. Thirty-four patients had been irradiated for left-sided tumors, 33 for right-sided tumors, and 23 patients had not been treated with radiotherapy. The radiotherapy (conventional roentgen, electron beams, and high-energy photon beams combined, in each patient) included the chest wall and the regional lymph nodes, with a specified target dose of 38-48 Gy, administered in daily fractions of 1.9-2.4 Gy, 5 days/week. RESULTS: No cardiac deaths were found among the original 275 patients randomized to adjuvant therapy. In the 90 patients examined, abnormal findings were recorded for ECG (14 patients), exercise test (5 patients), myocardial scintigraphy (6 patients), thickening of valve cusps (14 patients), and mild valvular regurgitation (20 patients). All patients had normal systolic function. Diastolic dysfunction was observed in 6 patients (abnormal relaxation in 4 patients and restrictive filling abnormality in 2 patients). Although no significant differences were found between the 3 study groups, there was a tendency to more abnormal findings after radiotherapy. CONCLUSION: Women younger than 50 years of age at the time of adjuvant radiotherapy following mastectomy in early breast cancer, had no serious cardiac sequelae 13 years (median) later, despite partly old-fashioned radiation techniques.

Methyl-GAG, ifosfamide, methotrexate and etoposide (MIME) as salvage therapy for Hodgkin's disease: a prospective study.

This study presents the results of a prospective study of methyl-gag, ifosfamide, methotrexate and etoposide (MIME) as salvage regimen for Hodgkin's disease (HD) in Sweden. Sixty-four patients with recurrent or refractory HD were treated with MIME between July 1988 and December 1993. All patients except one had, earlier, been treated with and failed consecutive or alternating MOPP and ABVD. Median age was 37 yr (range 14-73). Twenty patients (31%) achieved a complete remission (CR) and 17 (27%) a partial remission (PR), giving an overall response rate of 58%. The 5-yr survival for all patients was 43%. In a multivariate analysis, the most important factors predicting a poor survival were the presence of extranodal disease at relapse, male gender and high age. Twenty-nine patients were treated with high-dose chemotherapy with stem-cell rescue after MIME. Those patients had a similar survival compared to the patients responding to MIME but not treated with high-dose chemotherapy. We conclude that MIME induces remissions in a high proportion of patients with recurrent and refractory HD with acceptable toxicity. The remissions probably need consolidation, but the nature of this consolidation is still controversial.

Acceleration of amyloid protein A amyloidosis by amyloid-like synthetic fibrils.

Amyloid protein A (AA) amyloidosis is a consequence of some long-standing inflammatory conditions, and subsequently, an N-terminal fragment of the acute phase protein serum AA forms beta-sheet fibrils that are deposited in different tissues. It is unknown why only some individuals develop AA amyloidosis. In the mouse model, AA amyloidosis develops after approximately 25 days of inflammatory challenge. This lag phase can be shortened dramatically by administration of a small amount of amyloid extract containing an as yet undefined amyloid-enhancing factor. In the present study, we show that preformed amyloid-like fibrils made from short synthetic peptides corresponding to parts of several different amyloid fibril proteins exert amyloidogenic enhancing activity when given i.v. to mice at the induction of inflammation. We followed i.v. administered, radiolabeled, heterologous, synthetic fibrils to the lung and to the perifollicular area in the spleen and found that new AA-amyloid fibrils developed on these preformed fibrils. Our findings thus show that preformed, synthetic, amyloid-like fibrils have an in vivo nidus activity and that amyloid-enhancing activity may occur, at least in part, through this mechanism. Our findings also show that fibrils of a heterologous chemical nature exert amyloid-enhancing activity.