Evidence for Complex Dynamics in Glassy Fast Ion Conductors: The Case of Sodium Thiosilicates.

Classical molecular dynamics is used to study the dynamics of alkali ions in a promising fast ion conductor glass system, i.e., Na2S-SiS2. Diffusion in such thiosilicates is found to display various salient features of alkali silicates, i.e., channel-like diffusion with typical length scales emerging as the temperature is decreased to the glassy state, and Arrhenius behavior for both Na ion diffusivity and calculated conductivity. The dynamics appears, however, to be largely heterogeneous as manifested by fast and slow Na ion motion at intermediate times, both in the high-temperature liquid and in the glassy state. In the former, a diffusion-limited regime is found due to the increased motion of the network-forming species that limits the Na ion dynamics, whereas at low temperatures, the typical dynamical heterogeneities are recovered as observed close to the glass transition.

Cytomegalovirus (CMV) Disease Despite Weekly Preemptive CMV Strategy for Recipients of Solid Organ and Hematopoietic Stem Cell Transplantation.

BACKGROUND: Transplant recipients presenting with cytomegalovirus (CMV) disease at the time of diagnosis of CMV DNAemia pose a challenge to a preemptive CMV management strategy. However, the rate and risk factors of such failure remain uncertain. METHODS: Solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) recipients with a first episode of CMV polymerase chain reaction (PCR) DNAemia within the first year posttransplantation were evaluated (n = 335). Patient records were reviewed for presence of CMV disease at the time of CMV DNAemia diagnosis. The distribution and prevalence of CMV disease were estimated, and the odds ratio (OR) of CMV disease was modeled using logistic regression. RESULTS: The prevalence of CMV disease increased for both SOT and HSCT with increasing diagnostic CMV PCR load and with screening intervals >14 days. The only independent risk factor in multivariate analysis was increasing CMV DNAemia load of the diagnostic CMV PCR (OR = 6.16; 95% confidence interval, 2.09-18.11). Among recipients receiving weekly screening (n = 147), 16 (10.8%) had CMV disease at the time of diagnosis of CMV DNAemia (median DNAemia load 628 IU/mL; interquartile range, 432-1274); 93.8% of these cases were HSCT and lung transplant recipients. CONCLUSIONS: Despite application of weekly screening intervals, HSCT and lung transplant recipients in particular presented with CMV disease at the time of diagnosis of CMV DNAemia. Additional research to improve the management of patients at risk of presenting with CMV disease at low levels of CMV DNAemia and despite weekly screening is warranted.

Photodynamic therapy is more effective than imiquimod for actinic keratosis in organ transplant recipients: a randomized intraindividual controlled trial.

BACKGROUND: Actinic keratoses (AKs) in solid organ transplant recipients (OTRs) are difficult-to-treat premalignancies and comparison of topical therapies is therefore warranted. OBJECTIVES: In an intraindividual study to compare the efficacy and safety of field treatment with methyl aminolaevulinate photodynamic therapy (MAL-PDT) and imiquimod (IMIQ) for AKs in OTRs. METHODS: OTRs (n = 35) with 572 AKs (grade I-III) in two similar areas on the face, scalp, dorsal hands or forearms were included. All patients received one MAL-PDT and one IMIQ session (three applications per week for 4 weeks) in each study area according to randomization. Treatments were repeated after 2 months (IMIQ) and 3 months (PDT) in skin with incomplete AK response. Outcome measures were complete lesion response (CR), skin reactions, laboratory results and treatment preference. RESULTS: The majority of study areas received two treatment sessions (PDT n = 25 patients; IMIQ n = 29 patients). At 3 months after two treatments, skin treated with PDT achieved a higher rate of CR (AK I-III median 78%; range 50-100) compared with IMIQ-treated skin areas (median 61%, range 33-100; P < 0·001). Fewer emergent AKs were seen in PDT-treated skin vs. IMIQ-treated skin (0·7 vs. 1·5 AKs, P = 0·04). Patients developed more intense inflammatory skin reactions following PDT, which resolved more rapidly compared with IMIQ (median 10 days vs. 18 days, P < 0·01). Patient preference (P = 0·47) and cosmesis (P > 0·30) were similar for PDT and IMIQ. CONCLUSIONS: Compared with IMIQ, PDT treatment obtained a higher rate of AK clearance at 3-month follow-up and achieved shorter-lasting, but more intense, short-term skin reactions.

Risk of infectious diseases among first-degree relatives of transplant recipients who develop CMV infection: is the infectious phenotype inheritable?

Transplant recipients are at high risk of cytomegalovirus (CMV) infection. Mechanisms explaining the variation in risk of infections are far from fully elucidated. We hypothesised that host genetics explains part of the variation in risk of infection and examined if relatives of recipients with CMV infection have higher rates of severe infections compared to relatives of recipients without this infectious phenotype. In a register-based study, we included first-degree relatives of transplant recipients and examined the risk of hospitalisation due to overall infection or viral infection and risk of death among relatives of recipients who developed CMV infection within the first year of transplantation compared to relatives of recipients without CMV. Analyses were adjusted for sex, age and calendar year. We included 4470 relatives who were followed for 103,786 person-years, median follow-up 24 years [interquartile range (IQR) 12-36]. There were a total of 1360 infection-related hospitalisations in the follow-up period, incidence rate (IR) 13.1/1000 person-years [95% confidence interval (CI), 12.4; 13.8]. 206 relatives were hospitalised with viral infection, IR 1.8/1000 person-years (95% CI, 1.6; 2.0). There was no increased risk of hospitalisation due to infections, IR ratio (IRR) 0.99 (95% CI, 0.88; 1.12), nor specifically viral infections, IRR 0.87 (95% CI, 0.63; 1.19), in relatives of recipients with CMV compared to relatives of recipients without CMV. Also, no difference was seen in analyses stratified by transplant type, family relation and CMV serostatus. The risk of hospitalisation due to infection is not increased among first-degree relatives of transplant recipients with CMV infection compared to relatives of recipients without CMV.

Case Report: Renal Transplantation in Patients with Pre-existing Hypogammaglobulinemia.

Hypogammaglobulinemia (HGG) is well-characterized as a common phenomenon after kidney transplantation. However, no reports of pre-existing HGG from kidney transplantation seem to be available. We have reviewed three patients who developed HGG prior to kidney transplantation, and all three were treated successfully with immunoglobulin replacement therapy before and after kidney transplantation. The kidney grafts were functioning at follow-up 1.5-8 years (mean: 3.6 years) after transplantation, and there were no diagnosed episodes of clinical rejections and no severe infection complications post-transplantation.

Scandiatransplant acceptable mismatch program (STAMP) a bridge to transplanting highly immunized patients.

BACKGROUND: Highly immunized patients are a challenge for organ transplantation programs. One way of increasing the likelihood of transplantation in this group of patients is to expand the possible donations by defining acceptable HLA mismatches. In the Scandiatransplant Acceptable Mismatch Program (STAMP), a de-centralized approach has been implemented in 2009. AIMS: The program has been improved during the years from utilizing HLA-A, -B, -DR matching only to include typing of all deceased donors for HLA-A, -B, -C, -DRB1 and -DQB1. The calculation of a transplantability score (TS) has been introduced in order to take both HLA and AB0 into consideration resulting in a more realistic picture of the transplantability chance. MATERIALS AND METHODS: Patients were selected for eligibility and results of immunisation status were prepared in each of the 9 tissue typing laboratories, while access to the program is finally governed by a common steering group of immunologists and clinicians. RESULTS: In the period from March 2009 until February 2015, 96 patients were transplanted within this program. The mean recipient age was 49 years and 57% were females, 30% of the patients were first transplants and of these 93% were females. The majority of the patients had 2-5 HLA-A, -B. -DR mismatches. The allograft survival at 60 months was 79.1%. Applying the TS to the cohort confirmed that patients with a low TS score had longer waiting times. CONCLUSION: The program has matured during the years and now proves to be a valid approach for transplanting highly immunized patients.

The clinical utility of FDG PET/CT among solid organ transplant recipients suspected of malignancy or infection.

PURPOSE: Solid organ transplant (SOT) recipients are at high risk of developing infections and malignancies. 18F-FDG PET/CT may enable timely detection of these diseases and help to ensure early intervention. We aimed to describe the clinical utility of FDG PET/CT in consecutive, diagnostic unresolved SOT recipients transplanted from January 2004 to May 2015. METHODS: Recipients with a post-transplant FDG PET/CT performed as part of diagnostic work-up were included. Detailed chart reviews were done to extract relevant clinical information and determine the final diagnosis related to the FDG PET/CT. Based on á priori defined criteria and the final diagnosis, results from each scan were classified as true or false, and diagnostic values determined. RESULTS: Among the 1,814 recipients in the cohort, 145 had an FDG PET/CT performed; 122 under the indication of diagnostically unresolved symptoms with a suspicion of malignancy or infection. The remaining (N = 23) had an FDG PET/CT to follow-up on a known disease or to stage a known malignancy. The 122 recipients underwent a total of 133 FDG PET/CT scans performed for a suspected malignancy (66 %) or an infection (34 %). Sensitivity, specificity, and positive and negative predictive values of the FDG PET/CT in diagnosing these conditions were 97, 84, 87, and 96 %, respectively. CONCLUSION: FDG PET/CT is an accurate diagnostic tool for the work-up of diagnostic unresolved SOT recipients suspected of malignancy or infection. The high sensitivity and NPV underlines the potential usefulness of PET/CT for excluding malignancy or focal infections in this often complex clinical situation.

Clinical Application of Variation in Replication Kinetics During Episodes of Post-transplant Cytomegalovirus Infections.

BACKGROUND: Cytomegalovirus (CMV) infection in transplant recipients is reported to replicate with a doubling time of 1.2-2 days, and weekly screening is recommended for early diagnosis. We re-evaluated these features in our cohort of transplant recipients. METHODS: The CMV doubling time of the first CMV infection in the first year post-transplant could be calculated for 193 recipients of haematopoietic stem cell or solid organ transplantation. Factors determining the proportion of recipients with a high diagnostic CMV viral load (≥ 18,200 IU/mL) were explored using mathematical simulation. FINDINGS: The overall median doubling time was 4.3 days (IQR 2.5-7.8) and was not influenced by prior CMV immunity, or type of transplantation (p > 0.4). Assuming a fixed doubling time of 1.3 days and screening intervals of 7 or 10 days, 11.1% and 33.3% were projected to have a high CMV viral load at diagnosis, compared to 1.4% and 4.3% if the doubling time varies as observed in our cohort. Consistently, 1.9% of recipients screened weekly had a high diagnostic virus load. INTERPRETATION: Screening intervals can be extended to 10 days in cohorts with comparable CMV doubling time, whereas shorter than 7 days is required in cohorts with shorter doubling times to maintain pre-emptive screening quality.

Primary prevention of skin dysplasia in renal transplant recipients with photodynamic therapy: a randomized controlled trial.

Organ transplant recipients (OTRs) are at high risk of developing cutaneous squamous cell carcinoma (SCC); prevention includes early treatment of premalignant actinic keratosis (AK). Photodynamic therapy (PDT) is a noninvasive field therapy that reduces new AKs in patients with existing AK and delays SCC development in mice. We investigated the effect of repeated PDT over 5 years for primary prophylaxis of skin dysplasia. These data represent an interim analysis of an on-going randomized controlled trial. During 2008-2011, 25 renal transplant recipients with clinically normal skin were randomized to split-side PDT of the face, forearm and hand, the contralateral side serving as untreated control. Patients received PDT on inclusion and at 6-monthly intervals for 5 years. Blinded evaluation was performed at each visit. We found that prophylactic PDT significantly delayed onset of AK compared with untreated skin, p = 0.020. At 3-year follow-up, we observed AK in 63% of patients in untreated skin areas compared with 28% of patients in PDT-treated skin, with a total number of cumulated AKs in untreated skin (n = 43) compared with PDT-treated skin (n = 8), p = 0.005. These preliminary data indicate a novel approach to early prevention of skin dysplasia that may reduce morbidity from multiple AKs and SCCs in OTR.

Improved marathon performance by in-race nutritional strategy intervention.

It was tested whether a marathon was completed faster by applying a scientifically based rather than a freely chosen nutritional strategy. Furthermore, gastrointestinal symptoms were evaluated. Nonelite runners performed a 10 km time trial 7 weeks before Copenhagen Marathon 2013 for estimation of running ability. Based on the time, runners were divided into two similar groups that eventually should perform the marathon by applying the two nutritional strategies. Matched pairs design was applied. Before the marathon, runners were paired based on their prerace running ability. Runners applying the freely chosen nutritional strategy (n = 14; 33.6 ± 9.6 years; 1.83 ± 0.09 m; 77.4 ± 10.6 kg; 45:40 ± 4:32 min for 10 km) could freely choose their in-race intake. Runners applying the scientifically based nutritional strategy (n = 14; 41.9 ± 7.6 years; 1.79 ± 0.11 m; 74.6 ± 14.5 kg; 45:44 ± 4:37 min) were targeting a combined in-race intake of energy gels and water, where the total intake amounted to approximately 0.750 L water, 60 g maltodextrin and glucose, 0.06 g sodium, and 0.09 g caffeine per hr. Gastrointestinal symptoms were assessed by a self-administered postrace questionnaire. Marathon time was 3:49:26 ± 0:25:05 and 3:38:31 ± 0:24:54 hr for runners applying the freely chosen and the scientifically based strategy, respectively (p = .010, effect size=-0.43). Certain runners experienced diverse serious gastrointestinal symptoms, but overall, symptoms were low and not different between groups (p > .05). In conclusion, nonelite runners completed a marathon on average 10:55 min, corresponding to 4.7%, faster by applying a scientifically based rather than a freely chosen nutritional strategy. Furthermore, average values of gastrointestinal symptoms were low and not different between groups.

Disparities in policies, practices and rates of pediatric kidney transplantation in Europe.

We aimed to provide an overview of kidney allocation policies related to children and pediatric kidney transplantation (KTx) practices and rates in Europe, and to study factors associated with KTx rates. A survey was distributed among renal registry representatives in 38 European countries. Additional data were obtained from the ESPN/ERA-EDTA and ERA-EDTA registries. Thirty-two countries (84%) responded. The median incidence rate of pediatric KTx was 5.7 (range 0-13.5) per million children (pmc). A median proportion of 17% (interquartile range 2-29) of KTx was performed preemptively, while the median proportion of living donor KTx was 43% (interquartile range 10-52). The median percentage of children on renal replacement therapy (RRT) with a functioning graft was 62%. The level of pediatric prioritization was associated with a decreased waiting time for deceased donor KTx, an increased pediatric KTx rate, and a lower proportion of living donor KTx. The rates of pediatric KTx, distribution of donor source and time on waiting list vary considerably between European countries. The lack of harmonization in kidney allocation to children raises medical and ethical issues. Harmonization of pediatric allocation policies should be prioritized.

The time course of development and impact from viral resistance against ganciclovir in cytomegalovirus infection.

(Val)ganciclovir is used to treat cytomegalovirus (CMV) infection following solid organ (SOT) or hematopoietic stem cell (HSCT) transplantation. Treatment failures occur, but the contribution from 39 known ganciclovir-related mutations (GRMs) in the CMV-UL97 gene remains controversial. We propose a categorization of these GRMs potentially useful when interpreting sequence analyses in clinical settings. The UL97 gene was sequenced from first/recurrent CMV infections among consecutive SOT or HSCT recipients during 2004-2009. GRMs were categorized as: Signature GRM (sGRM) if in vitro ganciclovir IC(50) ratio for mutated versus wild-type virus >2 (n = 24); polymorphic GRM (pGRM) if ratio <2 (n = 15). (Val)ganciclovir treatment failure was defined as persistent viremia for 30 days or switch to foscarnet within this period. Of 99 (49 HSCT and 50 SOT) recipients with one CMV infection episode, 15 (13 HSCT and 2 SOT) experienced a total of 19 recurrent infection episodes. The prevalence of sGRM was 0% at start of first episode, whereas at start of recurrent episodes, prevalence was 37%. Only one sGRM was present at a time in individual patients. Patients with CMV containing an sGRM (vs. wild type)-but not with a pGRM-were at excess risk of treatment failure (odds ratio = 70.6 [95% CI:8.2-609.6]; p < 0.001). sGRMs emerged only following longer termed use of antiherpetic drugs and usually in recurrent CMV infection episodes. Risk of ganciclovir treatment failure was raised if an sGRM was detected.

Improved renal function after early conversion from a calcineurin inhibitor to everolimus: a randomized trial in kidney transplantation.

In an open-label, multicenter trial, de novo kidney transplant recipients at low to medium immunological risk were randomized at week 7 posttransplant to remain on CsA (n = 100, controls) or convert to everolimus (n = 102), both with enteric-coated mycophenolate sodium and corticosteroids. The primary endpoint, change in measured GFR (mGFR) from week 7 to month 12, was significantly greater with everolimus than controls: 4.9 (11.8) mL/min versus 0.0 (12.9) mL/min (p = 0.012; analysis of covariance [ANCOVA]). Per protocol analysis demonstrated a more marked difference: an increase of 8.7 (11.2) mL/min with everolimus versus a decrease of 0.4 (12.0) mL/min in controls (p < 0.001; ANCOVA). There were no differences in graft or patient survival. The 12-month incidence of biopsy-proven acute rejection (BPAR) was 27.5% (n = 28) with everolimus and 11.0% (n = 11) in controls (p = 0.004). All but two episodes of BPAR in each group were mild. Adverse events occurred in 95.1% of everolimus patients and 90.0% controls (p = 0.19), with serious adverse events in 53.9% and 38.0%, respectively (p = 0.025). Discontinuation because of adverse events was more frequent with everolimus (25.5%) than controls (3.0%; p = 0.030). In conclusion, conversion from CsA to everolimus at week 7 after kidney transplantation was associated with a greater improvement in mGFR at month 12 versus CNI-treated controls but discontinuations and BPAR were more frequent.

Phengite-based chronology of K- and Ba-rich fluid flow in two paleosubduction zones.

Subduction recycles aqueous fluids from slab and sediment to the mantle. Subduction zones are long-lived, but time scales for fluid-rock interaction within subduction complexes are uncertain. Large-ion lithophile elements (potassium and barium) were added to eclogite (subducted basalt) during high pressure/temperature metamorphism via phengite crystallization from subduction zone fluids. Phengite grains from eclogite blocks and their metasomatic selvages yielded 40Ar/39Ar ages across grains and between samples that indicate 25 and 60 million years of fluid-rock interaction in the Samana Complex, Dominican Republic, and the Franciscan Complex, California, respectively.

[TPO immunostaining of the solitary, cold thyroid nodules]. / TPO-immunfarvning af den solitaere, kolde thyreoideaknude.

INTRODUCTION: The chance of malignancy in scintigraphically cold thyroid nodules is 2-24%. Differentiation between malignant and benign cytology is difficult. The aim of this study was to evaluate the ability of immunostaining (MoAB47--raised against thyroid peroxidase (TPO)) to differentiate between malignant and benign cells taken from cold thyroid nodules by fine needle aspiration biopsy (FNAB) in order to reduce the number of unnecessary thyroid operations. MATERIALS AND METHODS: One hundred and eighty-one patients (150 female) with a scintigraphically cold, solitary thyroid nodule were entered between 1993 and 1996. Fifty-seven were excluded for various reasons. Material removed by FNAB was stained with MoAB47 and routine staining. Staining of 80% or more of the cells was considered benign, less than 80% was considered malignant. Routine staining of operatively removed material was used as the final diagnosis. RESULTS: A pattern with negative TPO staining was found in all lesions that were subsequently proved to be malignant. In all but one, the lesions subsequently diagnosed as being benign stained positive for TPO. The sensitivity and specificity were respectively 1.0 and 0.99. CONCLUSION: TPO immunostaining of material removed by FNAB is a powerful tool in the differentiation between benign and malignant tumours.

Folic acid enrichment of bread does not appear to affect zinc absorption in young women.

BACKGROUND: In several countries cereals are now enriched with folic acid to reduce the risk of neural tube defects. Human studies suggest that folic acid interferes with zinc absorption. This raises concerns about the zinc status of high-risk groups such as infants, pregnant women, and older persons. OBJECTIVE: We sought to determine the effect of added folic acid on zinc absorption from white bread with high and low zinc contents. DESIGN: Zinc absorption was measured in 15 healthy women (22-33 y), each of whom consumed 4 single meals spaced 2 wk apart in a randomized crossover design. The servings of bread (100 g) differed in zinc and folic acid contents as follows: A, 1.2 mg Zn and 17 microg folic acid; B, 1.2 mg Zn and 144 microg folic acid; C, 3.0 mg Zn and 17 microg folic acid; and D, 2.9 mg Zn and 144 microg folic acid. Meals were extrinsically labeled with 65Zn and absorption was estimated from whole-body retention measurements. Folate status was assessed by measuring plasma and erythrocyte folate and plasma homocysteine concentrations. RESULTS: Mean (+/-SD) zinc absorption did not differ significantly in relation to the folate content of the breads at either the low zinc content (38.8 +/- 13.5% and 40.6 +/- 16.5% for A and B, respectively; P = 0.74) or the high zinc content (26.7 +/- 9.3% and 22.7 +/- 6.6% for C and D, respectively; P = 0.16). There was no significant correlation between folate status and zinc absorption (r < 0.3, P > 0.1). CONCLUSION: Fortification of white bread with a commonly used amount of folic acid did not appear to influence zinc absorption at either a high or a low zinc content.

Green tea or rosemary extract added to foods reduces nonheme-iron absorption.

BACKGROUND: Phenolic compounds act as food antioxidants. One of the postulated mechanisms of action is chelation of prooxidant metals, such as iron. Although the antioxidative effect is desirable, this mechanism may impair the utilization of dietary iron. OBJECTIVE: We sought to determine the effect of phenolic-rich extracts obtained from green tea or rosemary on nonheme-iron absorption. DESIGN: Young women aged 19-39 y consumed test meals on 4 separate occasions. The meals were identical except for the absence (meal A) or presence (meal B) of a phenolic-rich extract from green tea (study 1; n = 10) or rosemary (study 2; n = 14). The extracts (0.1 mmol) were added to the meat component of the test meals. The meals were extrinsically labeled with either 55Fe or 59Fe and were consumed on 4 consecutive days in the order ABBA or BAAB. Iron absorption was determined by measuring whole-body retention of 59Fe and the ratio of 55Fe to 59Fe activity in blood samples. RESULTS: The presence of the phenolic-rich extracts resulted in decreased nonheme-iron absorption. Mean (+/-SD) iron absorption decreased from 12.1 +/- 4.5% to 8.9 +/- 5.2% (P < 0.01) in the presence of green tea extract and from 7.5 +/- 4.0% to 6.4 +/- 4.7% (P < 0.05) in the presence of rosemary extract. CONCLUSION: Phenolic-rich extracts used as antioxidants in foods reduce the utilization of dietary iron.

Thyroperoxidase (TPO) immunostaining of the solitary cold thyroid nodule.

OBJECTIVE: To evaluate the value of immunostaining using the monoclonal antibody (MoAB47) against thyroperoxidase (TPO) in distinguishing between benign and malignant tumour cells in fine needle aspiration cytology (FNAC) samples obtained from a solitary cold nodule of the thyroid gland for the purpose of strengthening the indication for thyroid surgery. DESIGN: A prospective, immunocytochemical study of FNACs taken from patients with solitary cold thyroid nodules who presented to Rigshospitalet, Copenhagen, Denmark, during the period April 1993 to May 1996. The first sample series was taken perioperatively in order to test the utility of the method. In the second part of the study samples were obtained preoperatively by ultrasonic guided aspiration. Tissue sections from the nodules obtained during a subsequent operation served as controls. PATIENTS: One hundred and eighty-one patients, 150 women and 31 men, were studied. The age range was 14-89 years with a median age of 44 years. Fifty-seven patients were excluded from the study for various reasons leaving us with a total of 124 nodules from 124 patients for final evaluation. METHODS: FNAC cells and corresponding nodular tissue were stained by immunocyto- and immuno-histochemistry using MoAb47 and by routine staining methods. Samples were considered benign if 80% or more of the epithelial-looking cells of both the FNACs and the histological tissue sections of the nodule were stained by TPO. Consequently, samples were considered malignant if more than 20% of the epithelial-looking cells failed to stain for TPO. Routinely stained tissue cells and sections served as diagnostic controls. RESULTS: A pattern with negative TPO staining was found in all lesions which, by conventional histological staining, were subsequently proven to be malignant. A universal and reliable, positive TPO staining pattern was found in all subsequently proven benign lesions, with the exception of one out of 26 follicular adenomas. This gave the method a sensitivity of 1.0 (negative TPO staining = malignancy in 27 out of 27) and a specificity of 0.99 (positive TPO staining = benign lesion, in 96 out of 97). Positive and negative predictive values were 0.96 and 1.00 respectively. CONCLUSION: Thyroperoxidase immunostaining of fine needle aspirates from solitary, scintigraphically cold nodules of the thyroid gland has proved to be an important and reliable diagnostic tool for distinguishing between benign and malignant nodules. Thus, patients might be spared further surgery if not otherwise indicated.

Use of fluorine-18 fluorodeoxyglucose positron emission tomography in the detection of silent metastases from malignant melanoma.

Correct staging is crucial for the management and prognosis of patients with malignant melanoma. The aim of this prospective study was to compare staging by whole-body positron emission tomography using fluorine-18 fluorodeoxyglucose (18F-FDG) with staging by conventional methods. Thirty-eight patients with malignant melanoma of clinical stage II (local recurrence, in-transit and regional lymph node metastases) or III (metastases to other sites than in stage II) were included in the study. The results of the PET scans were compared with those obtained by clinical examination, computed tomography, ultrasound, radiography, and liver function tests and histology or clinical follow-up. With 18F-FDG PET we found for all foci a sensitivity of 97% and a specificity of 56%, compared with 62% and 22%, respectively, when using routine methods. For intra-abdominal foci, the sensitivity and specificity were 100% for both 18F-FDG PET and routine methods. Corresponding figures for pulmonary/intrathoracic foci were 100% and 33%, respectively. Of the patients included in this study, 34% would not have been staged correctly by conventional methods alone. We conclude from this study that 18F-FDG PET is a sensitive method superior to conventional methods for detecting widespread metastases from malignant melanoma. Mutilating surgery of no benefit can thereby be avoided. 18F-FDG PET is useful as a supplement to clinical examination in melanoma staging.