Quantitative evaluation of the tibiofemoral joint cartilage by T2 mapping in patients with acute anterior cruciate ligament injury vs contralateral knees: results from the subacute phase using data from the NACOX study cohort.

OBJECTIVE: Immediate cartilage structural alterations in the acute phase after an anterior cruciate ligament (ACL) rupture may be a precursor to posttraumatic osteoarthritis (PTOA) development. Our aim was to describe changes in cartilage matrix in the subacute phase of the acutely ACL-injured knee compared to the contralateral uninjured knee. DESIGN: Participants (n = 118) aged 15-40 years with an acute ACL injury were consecutively included in subacute phase after acute ACL-injury and underwent MRI (mean 29 days post trauma) of both knees. Mean T2 relaxation times, T2 spatial coefficient of variation and cartilage thickness were determined for different regions of the tibiofemoral cartilage. Differences between the acutely ACL-injured and uninjured knee were evaluated using Wilcoxon signed-rank test. RESULTS: T2 relaxation time in injured knees was increased in multiple cartilage regions from both medial and lateral compartment compared to contralateral knees, mostly in medial trochlea and posterior tibia (P-value<0.001). In the same sites of injured knees, we observed significantly thinner cartilage. Moreover, injured knees presented shorter T2 relaxation time in superficial cartilage on lateral central femur and trochlea (P-value<0.001), and decreased T2 spatial coefficient of variation in lateral trochlea and load bearing regions of medial-central femoral condyle and central tibia in both compartments. CONCLUSION: Small but statistically significant differences were observed in the subacute phase between ACL-injured and uninjured knee in cartilage T2 relaxation time and cartilage thickness. Future longitudinal observations of the same cohort will allow for better understanding of early development of PTOA. TRIAL REGISTRATION NUMBER: NCT02931084.

Prognostic factors for tibiofemoral and patellofemoral osteoarthritis 32-37 years after anterior cruciate ligament injury managed with early surgical repair or rehabilitation alone.

OBJECTIVE: Explore prognostic factors for tibiofemoral (TFJ) and patellofemoral (PFJ) radiographic osteoarthritis (ROA) and 'symptoms plus ROA' (SOA), 32-37 years following anterior cruciate ligament (ACL) injury. DESIGN: Exploratory analysis, longitudinal cohort. METHODS: In 1980-1985, 251 patients aged 15-40 years with acute ACL rupture were allocated to early augmented or non-augmented repair (5 ± 4 days post-injury) plus rehabilitation, or rehabilitation alone. 127 of 190 participants who completed follow-up questionnaires were eligible. We classified ROA as TFJ/PFJ K&L Grade ≥2, and SOA as ROA plus pain and/or symptoms. Multivariable age-adjusted logistic regression investigated potential prognostic factors (assessed at 4 ± 1 year follow-up: ACL treatment, isokinetic quadriceps/hamstrings strength, single-leg-hop for distance, knee flexion/extension deficit, knee laxity, Tegner Activity Scale, Lysholm Scale; sex, baseline meniscus status). RESULTS: 127 patients were aged 58 ± 6 years; BMI 27 ± 4 kg/m2; 28% female; 59% had TFJ-ROA, 48% had TFJ-SOA (including n = 9 knee-arthroplasties), 36% had PFJ-ROA; 27% had PFJ-SOA. Baseline meniscus surgery was a prognostic factor for TFJ-ROA (multivariable age-adjusted odds ratio (95% CI): 3.0 (1.2, 7.8)). A single-leg-hop limb symmetry index (LSI) < 90% was a prognostic factor for PFJ-ROA (5.1 (1.4, 18.7)) and PFJ-SOA (4.9 (1.2, 19.7)). Hamstrings strength LSI <90% was a prognostic factor for PFJ-SOA (5.0 (1.3, 19.3)). ACL treatment with rehabilitation-alone was associated with an 80% reduction in the odds of PFJ-SOA (0.2 (0.1-0.7)), compared with early ACL-repair. CONCLUSIONS: These findings are hypothesis generating, research is needed to determine whether ACL-injured individuals with these characteristics benefit from interventions to prevent or delay the onset of osteoarthritis.

Translation and testing of measurement properties of the Swedish version of the IKDC subjective knee form.

To translate to Swedish language and cross-culturally adapt the IKDC-SKF and to test the measurement properties of the Swedish version of IKDC-SKF in ACL-injured patients undergoing reconstruction surgery.The translation and cross-cultural adaption was performed according to guidelines. Seventy-six patients with an ACL injury filled out the IKDC-SKF and other questionnaires before ACL reconstruction and at 4, 6, and 12 months after surgery. A total of 203 patients from the Swedish ACL Registry participated at 8 months post-operative. Measurement properties were tested according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines.The Swedish IKDC-SKF had high internal consistency (Cronbach's alpha=0.90) and test-retest reliability (ICC2,1 =0.92, CI 95%: 0.81-0.97, P<.001). A single factor solution accounted for 46.1% of the variance in IKDC-SKF scores. Criterion validity was moderate to high. All ten predefined hypotheses for hypothesis testing were confirmed. The six hypotheses for responsiveness testing were confirmed. The effect size was 1.8, the standardized response mean was 1.9, the and minimal clinically important difference was 13.9 points.The Swedish version of the IKDC-SKF had good measurement properties and can be recommended for use in a population of ACL-deficient patients undergoing ACL reconstruction.

Comparison of patient-reported outcomes among those who chose ACL reconstruction or non-surgical treatment.

The aim of our study was to cross-sectionally compare patient-reported knee function outcomes between people who chose non-surgical treatment for ACL injury and those who chose ACL reconstruction. We extracted Knee Injury and Osteoarthritis Outcome Score (KOOS) and EuroQoL-5D data entered into the Swedish National ACL Registry by patients with a non-surgically treated ACL injury within 180 days of injury (n = 306), 1 (n = 350), 2 (n = 358), and 5 years (n = 114) after injury. These data were compared cross-sectionally to data collected pre-operatively (n = 306) and at 1 (n = 350), 2 (n = 358), and 5 years (n = 114) post-operatively from age- and gender-matched groups of patients with primary ACL reconstruction. At the 1 and 2 year comparisons, patients who chose surgical treatment reported superior quality of life and function in sports (1 year mean difference 12.4 and 13.2 points, respectively; 2 year mean difference 4.5 and 6.9 points, respectively) compared to those who chose non-surgical treatment. Patients who chose ACL reconstruction reported superior outcomes for knee symptoms and function, and in knee-specific and health-related quality of life, compared to patients who chose non-surgical treatment.

Fight or flight? - Flight increases immune gene expression but does not help to fight an infection.

Flight represents a key trait in most insects, being energetically extremely demanding, yet often necessary for foraging and reproduction. Additionally, dispersal via flight is especially important for species living in fragmented landscapes. Even though, based on life-history theory, a negative relationship may be expected between flight and immunity, a number of previous studies have indicated flight to induce an increased immune response. In this study, we assessed whether induced immunity (i.e. immune gene expression) in response to 15-min forced flight treatment impacts individual survival of bacterial infection in the Glanville fritillary butterfly (Melitaea cinxia). We were able to confirm previous findings of flight-induced immune gene expression, but still observed substantially stronger effects on both gene expression levels and life span due to bacterial infection compared to flight treatment. Even though gene expression levels of some immunity-related genes were elevated due to flight, these individuals did not show increased survival of bacterial infection, indicating that flight-induced immune activation does not completely protect them from the negative effects of bacterial infection. Finally, an interaction between flight and immune treatment indicated a potential trade-off: flight treatment increased immune gene expression in naïve individuals only, whereas in infected individuals no increase in immune gene expression was induced by flight. Our results suggest that the up-regulation of immune genes upon flight is based on a general stress response rather than reflecting an adaptive response to cope with potential infections during flight or in new habitats.

Factors associated with playing football after anterior cruciate ligament reconstruction in female football players.

This study investigated whether player-related factors (demographic, personality, or psychological factors) or the characteristics of the anterior cruciate ligament (ACL) injury were associated with the return to playing football in females after ACL reconstruction (ACLR). We also compared current knee function, knee related quality of life and readiness to return to sport between females who returned to football and those who had not returned. Females who sustained a primary ACL rupture while playing football and underwent ACLR 6-36 months ago were eligible. Of the 460 contacted, 274 (60%) completed a battery of questionnaires, and 182 were included a median of 18 months (IQR 13) after ACLR. Of these, 94 (52%) returned to football and were currently playing, and 88 (48%) had not returned. Multiple logistic regression analysis identified two factors associated with returning to football: short time between injury and ACLR (0-3 months, OR 5.6; 3-12 months OR 4.7 vs reference group > 12 months) and high motivation. Current players showed higher ratings for current knee function, knee-related quality of life, and psychological readiness to return to sport (P < 0.001). Undergoing ACLR sooner after injury and high motivation to return to sports may impact a player's return to football after ACLR.

Temperature- and sex-related effects of serine protease alleles on larval development in the Glanville fritillary butterfly.

The body reserves of adult Lepidoptera are accumulated during larval development. In the Glanville fritillary butterfly, larger body size increases female fecundity, but in males fast larval development and early eclosion, rather than large body size, increase mating success and hence fitness. Larval growth rate is highly heritable, but genetic variation associated with larval development is largely unknown. By comparing the Glanville fritillary population living in the Åland Islands in northern Europe with a population in Nantaizi in China, within the source of the post-glacial range expansion, we identified candidate genes with reduced variation in Åland, potentially affected by selection under cooler climatic conditions than in Nantaizi. We conducted an association study of larval growth traits by genotyping the extremes of phenotypic trait distributions for 23 SNPs in 10 genes. Three genes in clip-domain serine protease family were associated with larval growth rate, development time and pupal weight. Additive effects of two SNPs in the prophenoloxidase-activating proteinase-3 (ProPO3) gene, related to melanization, showed elevated growth rate in high temperature but reduced growth rate in moderate temperature. The allelic effects of the vitellin-degrading protease precursor gene on development time were opposite in the two sexes, one genotype being associated with long development time and heavy larvae in females but short development time in males. Sexually antagonistic selection is here evident in spite of sexual size dimorphism.

Knee arthroscopic surgery is beneficial to middle-aged patients with meniscal symptoms: a prospective, randomised, single-blinded study.

OBJECTIVE: There is no evidence that a knee arthroscopy is more beneficial to middle-aged patients with meniscal symptoms compared to other treatments. This randomised controlled trial aimed to determine whether an arthroscopic intervention combined with a structured exercise programme would provide more benefit than a structured exercise programme alone for middle-aged patients with meniscal symptoms that have undergone physiotherapy. METHOD: 150 out of 179 eligible patients, aged 45 to 64 (mean:54 ± 5), symptom duration more than 3 months and standing X-ray with Ahlbäck grade 0, were randomised to: (1) a physiotherapy appointment within 2 weeks of inclusion that included instructions for a 3-month exercise programme (non-surgery group); or (2) the same as (1) plus, within 4 weeks of inclusion, knee arthroscopy for resection of any significant meniscal injuries (surgery group). The primary outcome was change in pain at 12 months, assessed with the Knee Injury and Osteoarthritis Outcome Score (KOOSPAIN). RESULTS: In the Intention-To-Treat analysis, pain at 12 months was significantly lower in the surgery than in the non-surgery group. The change in KOOSPAIN was significantly larger in the surgery than in the non-surgery group (between-group difference was 10.6 points of change; 95% CI: 3.4 to 17.7, P = 0.004). The As-Treated analysis results were consistent with the Intention-To-Treat analysis results. CONCLUSION: Middle-aged patients with meniscal symptoms may benefit from arthroscopic surgery in addition to a structured exercise programme. Patients' age or symptom history (i.e., mechanical symptoms or acute onset of symptoms) didn't affect the outcome. TRIAL REGISTRATION: NCT01288768.

Translation and measurement properties of the Swedish version of ACL-Return to Sports after Injury questionnaire.

Psychological factors may be a hindrance for returning to sport after an anterior cruciate ligament (ACL) reconstruction. The ACL-Return to Sport after Injury scale (ACL-RSI) measures athletes' emotions, confidence in performance, and risk appraisal in relation to return to sport. The aim of this study was to translate the ACL-RSI scale from English to Swedish and to examine some of the measurement properties of the Swedish version. The ACL-RSI was translated and culturally adapted. A professional expert group and five patients evaluated face validity. One hundred and eighty-two patients completed the translated ACL-RSI, a project-specific questionnaire, the Tampa Scale of Kinesiophobia (TSK), the Knee-Self-Efficacy Scale (K-SES), the Multidimensional Health Locus of Control (MHLC-C), the Knee injury and Osteoarthritis Outcome Score (KOOS), and the Anterior Cruciate Ligament-Quality of Life (ACL-QoL) questionnaires. Fifty-three patients answered the ACL-RSI twice to examine reproducibility. The ACL-RSI showed good face validity, internal consistency (Cronbach's alpha = 0.948), low floor and ceiling effects and high construct validity when evaluated against the TSK, K-SES, MHLC-C, KOOS, and ACL-QoL scales. The reproducibility was also high (intra-class correlation = 0.893). Therefore, the ACL-RSI can be used to evaluate psychological factors relevant to returning to sport after ACL reconstruction surgery.

Early E-modulus of healing Achilles tendons correlates with late function: similar results with or without surgery.

Non-operative treatment of Achilles tendon ruptures is associated with an increased risk of rerupture. We hypothesized that this is due to inferior mechanical properties during an early phase of healing, and performed a randomized trial, using a new method to measure the mechanical properties. Tantalum markers were inserted in the tendon stumps, and tendon strain at different loadings was measured by stereo-radiography (Roentgen stereophotogrammetric analysis) at 3, 7 and 19 weeks and 18 months after injury. Thirty patients were randomized to operative or non-operative treatment. The primary out-come variable was an estimate for the modulus of elasticity at 7 weeks. Strain per force, cross-sectional area and tendon elongation were also measured. The functional outcome variable was the heel-raise index after 18 months. There was no difference in the mean modulus of elasticity or other mechanical or functional variables between operative and non-operative treatments at any time-point, but strain per force at 7 and 19 weeks had a significantly larger variation in the non-operative group. This group, therefore, might contain more outliers with poor healing. The modulus of elasticity at 7 weeks correlated with the heel-raise index after 18 months in both treatment groups (r(2) =0.75; P=0.0001). This correlation is an intriguing finding.

Functional genomics of life history variation in a butterfly metapopulation.

In fragmented landscapes, small populations frequently go extinct and new ones are established with poorly understood consequences for genetic diversity and evolution of life history traits. Here, we apply functional genomic tools to an ecological model system, the well-studied metapopulation of the Glanville fritillary butterfly. We investigate how dispersal and colonization select upon existing genetic variation affecting life history traits by comparing common-garden reared 2-day adult females from new populations with those from established older populations. New-population females had higher expression of abdomen genes involved in egg provisioning and thorax genes involved in the maintenance of flight muscle proteins. Physiological studies confirmed that new-population butterflies have accelerated egg maturation, apparently regulated by higher juvenile hormone titer and angiotensin converting enzyme mRNA, as well as enhanced flight metabolism. Gene expression varied between allelic forms of two metabolic genes (Pgi and Sdhd), which themselves were associated with differences in flight metabolic rate, population age and population growth rate. These results identify likely molecular mechanisms underpinning life history variation that is maintained by extinction-colonization dynamics in metapopulations.

Tibial translation and muscle activation during rehabilitation exercises 5 weeks after anterior cruciate ligament reconstruction.

The aim of this study was to compare different rehabilitation exercises with respect to dynamic anterior tibial translation and muscle activation 5 weeks after an anterior cruciate ligament (ACL) reconstruction. Another aim was to compare the ACL-reconstructed knee with the ACL-injured and the uninjured knees for differences in anterior tibial translation and muscle activation during the exercises. Sagittal tibial translation and muscle activation were measured during the Lachman test (static translation) and during seven rehabilitation exercises (dynamic translation) in 19 patients. Results obtained 5 weeks after ACL reconstruction were compared with those obtained before the ACL reconstruction (ACL-deficient and uninjured knee). After ACL reconstruction the seated knee extension produced more anterior tibial translation than the straight leg raise and standing on one leg. The ACL reconstruction reduced the static and the dynamic tibial translation and the tibial translations measured in ACL-reconstructed knees were similar to those measured in uninjured knees. After ACL reconstruction, the patients used a joint stiffening strategy that used more hamstring activation and reduced the dynamic tibial translation. Although all exercises tested are suitable for rehabilitation after ACL reconstruction, to protect the graft from excessive strain, the straight leg raise and squat on one leg are preferable for quadriceps training in the early phase of rehabilitation.

Floor cleaning: effect on bacteria and organic materials in hospital rooms.

Routine surface cleaning is recommended to control the spread of pathogens in hospital environments. In Norway, ordinary cleaning of patient rooms is traditionally performed with soap and water. In this study, four floor-mopping methods--dry, spray, moist and wet mopping--were compared by two systems using adenosine triphosphate (ATP) bioluminescence (Hygiena and Biotrace). These systems assess residual organic soil on surfaces. The floor-mopping methods were also assessed by microbiological samples from the floor and air, before and after cleaning. All methods reduced organic material on the floors but wet and moist mopping seemed to be the most effective (P < 0.001, P < 0.011, respectively, ATP Hygiena). The two ATP methods were easy to use, although each had their own reading scales. Cleaning reduced organic material to 5-36% of the level present before cleaning, depending upon mopping method. All four mopping methods reduced bacteria on the floor from about 60-100 to 30-60 colony-forming units (cfu)/20cm2 floor. Wet, moist and dry mopping seemed to be more effective in reducing bacteria on the floor, than the spray mopping (P=0.007, P=0.002 and P=0.011, respectively). The burden of bacteria in air increased for all methods just after mopping. The overall best cleaning methods seemed to be moist and wet mopping.

Fitness differences associated with Pgi SNP genotypes in the Glanville fritillary butterfly (Melitaea cinxia).

Allozyme variation at the phosphoglucose isomerase (PGI) locus in the Glanville fritillary butterfly (Melitaea cinxia) is associated with variation in flight metabolic rate, dispersal rate, fecundity and local population growth rate. To map allozyme to DNA variation and to survey putative functional variation in genomic DNA, we cloned the coding sequence of Pgi and identified nonsynonymous variable sites that determine the most common allozyme alleles. We show that these single-nucleotide polymorphisms (SNPs) exhibit significant excess of heterozygotes in field-collected population samples as well as in laboratory crosses. This is in contrast to previous results for the same species in which other allozymes and SNPs were in Hardy-Weinberg equilibrium or exhibited an excess of homozygotes. Our results suggest that viability selection favours Pgi heterozygotes. Although this is consistent with direct overdominance at Pgi, we cannot exclude the possibility that heterozygote advantage is caused by the presence of one or more deleterious alleles at linked loci.

Anterior positioning of tibia during motion after anterior cruciate ligament injury.

PURPOSE: The purpose of this study was to describe the sagittal tibial translation and EMG activity of muscles v. medialis and lateralis, gastrocnemius, and hamstrings, during common locomotion, in patients with an anterior cruciate ligament deficiency (ACL-def) and uninjured controls. METHODS: In 12 ACL-def patients and 17 controls, sagittal tibial translation was registered with the CA-4000 electrogoniometer during level walking, cutting, and stair walking. Tibial position at each flexion angle was expressed relative to the femuro-tibial position at passive knee extension. EMG activity, measured with ME-4000, was normalized to the individual maximum isometric voluntary contraction for each muscle. RESULTS: During the weight-bearing phase of motion, the tibia was anteriorly positioned in all legs. In the injured leg, the tibia translated more rapidly to an anterior position that was maintained for a longer time during the gait cycle. In the noninjured knees, motions with increased load lead to an increased anterior tibial translation in contrast to the injured knees, where the maximum displacement was already reached during level walking. The quadriceps and gastrocnemius muscles were simultaneously active during stance phase. Hamstrings were mainly active when the knee was close to extension and translation increased in spite of this activity. CONCLUSIONS: The mechanism of the anterior positioning of tibia is qualitatively similar in the normal and the injured knee, but that position is obtained much further forward in the ACL deficient knee. Quadriceps and gastrocnemius muscles seem to work synergistically to stabilize the knee by maintaining the anterior position of tibia during weight-bearing motion. The role of hamstrings to restrict anterior translation is questioned.

Anterior tibial translation during different isokinetic quadriceps torque in anterior cruciate ligament deficient and nonimpaired individuals.

STUDY DESIGN: Factorial quasi-experimental design. OBJECTIVES: To quantify the effect of different levels of isokinetic concentric and eccentric knee extensor torques on the anterior tibial translation in subjects with anterior cruciate ligament (ACL) deficiency. Electromyogram (EMG) activity of 4 leg muscles was recorded in order to detect any co-activation of extensors and flexors. BACKGROUND: The rehabilitation after an ACL injury is of importance for the functional outcome of the patient. In order to construct a rehabilitation program after that injury, it is important to understand the in vivo relationships between muscle force and tibial translation. METHODS AND MEASURES: Twelve patients with unilateral ACL injury and 11 uninjured volunteers performed 36 repetitions of a quadriceps contraction at different isokinetic concentric and eccentric torque levels, on a KinCom machine (60 degrees x s(-1)), with simultaneous recordings of tibial translation (CA-4000) and EMG activity from quadriceps and hamstrings muscles. Tibial translations and EMG levels were normalized to the maximum of each subject. RESULTS: The individual anterior tibial translation increased with increased quadriceps torque in a similar manner in both quadriceps contraction modes in all legs tested. During concentric mode, translation was similar in all groups, but during eccentric mode, the mean translation was 38% larger in the ACL injured knees. No quadriceps-hamstrings co-activation occurred in any test or group. CONCLUSIONS: An ACL deficient knee can limit the translation within a normal space during concentric muscle activity but not during eccentric activity. That limitation depends on other mechanisms than hamstrings co-activation.

Sagittal plane knee translation and electromyographic activity during closed and open kinetic chain exercises in anterior cruciate ligament-deficient patients and control subjects.

Using electrogoniometry and electromyography, we measured tibial translation and muscle activation in 12 patients with unilateral anterior cruciate ligament injury and in 12 control subjects. Measurements were made during an active extension exercise with 0-, 4-, and 8-kg weights and during squats on two legs and on one leg where the projection of the center of gravity was placed over, behind, and in front the feet. In the uninjured subjects, tibial translation increased with increasing load except during the squat with the center of gravity behind the feet, which produced the smallest translation. For the active extension exercises, translation was greater during eccentric activity. In the anterior cruciate ligament-injured knees, all squats resulted in similar translation, which was smaller than that during the active extension exercise. The highest muscle activation was seen during squats. Hamstring muscle activity was low. Increased static laxity in the anterior cruciate ligament-deficient knee can be controlled during closed but not during open kinetic chain exercises. Coactivation of the quadriceps and gastrocnemius muscles seems to be important for knee stability, whereas hamstring muscle coactivation was insignificant. To minimize sagittal translation during nonoperative management of anterior cruciate ligament-deficient knees, closed kinetic chain exercises are preferable to open kinetic chain exercises, and importance should be attached to the spontaneous coactivation of the quadriceps and gastrocnemius muscles.

Anterior tibial translation during eccentric, isokinetic quadriceps work in healthy subjects.

The effect of increasing isokinetic, eccentric quadriceps torques on sagittal translation of the tibia was examined in six healthy volunteers and compared to the translation at 20 degrees of knee flexion during a drawer test with 90 N force. The tibial translation increased in a linear fashion with a mean of 0.5 mm per 20% torque increase. In 20 degrees of knee flexion, 10% of eccentric quadriceps peak torque consumed 80% of the anterior tibial translation induced by the 90 N Lachman test while eccentric quadriceps peak torque utilized 100% of the translation at the same test. The in vivo relation between muscle force and tibial translation is of importance in the treatment of patients with injury to the cruciate ligaments. The results indicate that an already low eccentric quadriceps torque causes a tibial translation that reaches the limit of the passive knee joint displacement where strain is assumed to develop in the anterior cruciate ligament. Already low eccentric quadriceps torque levels may therefore be harmful during rehabilitation after anterior cruciate ligament surgery.

Effect of repeated sleep deprivation on clinical symptoms and the TRH test in endogenous depression.

Twenty-eight patients with endogenous depression were treated with repeated total sleep deprivation (TSD) as the only treatment. In eight patients complete remission was obtained, but an early relapse occurred in five, and after 6 months only three patients (11%) remained in remission. The remaining group of 20 patients with no or only a partial response to TSD also had a significant reduction of the score on the Hamilton Rating Scale (median 23 versus 17, P less than 0.01). A thyrotropin-releasing hormone (TRH) stimulating test was performed before and after TSD. According to previous studies an increase of the maximal response in serum thyrotropin (TSH) to TRH (delta delta max TSH greater than 2.0 microU/ml), after TSD was taken as a predictor of a favourable long-term outcome. Under blind conditions a correct prognosis was made in all patients (n = 8) from the group of responders. By comparison, only two of the 20 patients from the nonresponding group had a delta delta max TSH greater than 2.0 microU/ml after TSD.