Immediate and durable clinical improvement in the non-operated hand after contralateral surgery for patients with bilateral Carpal Tunnel Syndrome.

BACKGROUND: Little is known about clinical improvement in the non-operated hand after unilateral surgery for patients who present with bilateral carpal tunnel syndrome (CTS). In this prospective study of patients with bilateral CTS, we evaluated the clinical effects on the non-operated hand following unilateral contralateral carpal tunnel surgical release. MATERIAL AND METHODS: During a consecutive period of 22 months, 69 patients with bilateral CTS underwent unilateral open carpal tunnel release. Bilateral subjective and objective evaluations were performed pre-operatively, at days 2, 15 and 180 after surgery. Subjective evaluations, analysed with Student t test, included the Boston-Levine symptom severity score and a visual analogue scale including pain, nocturnal symptoms and numbness. A telephone survey was conducted 12 months after surgery. RESULTS: The Boston-Levine severity score of the contralateral non-operated hand decreased from 2.70 pre-operatively to 1.70 at 2 days (p < 0.001). The visual analogue pain score decreased at 2 days for 61 patients (88 %), whereas the nocturnal symptoms decreased or disappeared in 63 cases (91 %) and the paresthesia in 52 cases (75 %) (ps < 0.001). These beneficial effects were stable in time with no statistically significant change at 180 days. Overall, 58 patients (84 %) observed a total resolution or a significant improvement in their symptoms at 6 months. At 12 months, 100 % of patients responded to a telephone survey. Fifty one of them (74 %) reported minimal or no symptoms on the non-operated hand. Linear regression (analysis of variance [ANOVA]) showed that gender, age, professional status, duration of pre-operative symptoms and severity of electrophysiological disturbances were not predictive of post-operative evolution in the non-operated hand after unilateral surgery for CTS.

[Magnetic resonance imaging in meniscal bucket-handle tears]. / Imagerie par résonance magnétique dans les déchirures méniscales en anse de seau.

PURPOSE: To define MR signs of meniscal bucket-handle tears and evaluate the diagnostic efficiency of this technique. MATERIALS AND METHODS: Retrospective study of 30 patients with a meniscal bucket-handle tear and 30 with a different type of tear, all proven by arthroscopy. The following MR signs of a bucket-handle tear were evaluated: "separate meniscal fragment", "double posterior cruciate ligament", "snake sign" and "double anterior hom". RESULTS: A correct diagnosis of a bucket-handle tear was only made in 18/30 of patients. Several of the MR signs were seen in the same patient in 17 cases. A double posterior cruciate ligament was present only in cases of medial meniscus tears. The 12 menisci without these signs, and therefore not diagnosed as bucket-handle tears, were all classified as meniscal tears on the basis of signal extending to the meniscal surface. Nine of these were not displaced into the intercondylar notch at arthroscopy. The interobserver agreement was excellent: kappa = 0.88. CONCLUSION: The diagnosis of a bucket-handle meniscal tear, if it is displaced, can be made when one or more of the four MR evaluated signs are present. Other forms of meniscal tears are only exceptionally diagnosed as bucket-handle tears.

Familial adrenocorticotropin unresponsiveness associated with alacrima and achalasia: biochemical and molecular studies in two siblings with clinical heterogeneity.

UNLABELLED: The syndrome of familial adrenocorticotropin (ACTH) unresponsiveness is a rare form of primary adrenal insufficiency, usually without mineralocorticoid deficiency. It is characterized by elevated plasma ACTH concentrations and undetectable plasma cortisol levels not responding to exogenous ACTH. Alacrima and achalasia have also been occasionally associated with adrenal insufficiency (triple A syndrome). Pathogenetic mutations have been identified in the ACTH receptor gene in families with isolated familial ACTH unresponsiveness. Whether the ACTH receptor represents the locus of the defect for the triple A syndrome is not known. Here we report two siblings with familial ACTH unresponsiveness who were discrepant for skin pigmentation and mineralocorticoid function. In addition, achalasia and alacrima were documented only in the older sibling. The boy, studied at the age of 2 years, was hyperpigmented, in contrast to his normally pigmented sister, studied at the age of 9 years; basal plasma alpha-melanocyte stimulating hormone immunureactivity levels were 79 and 38 pg/ml, respectively (normal < 40 pg/ml). Furosemide-induced diuresis resulted in normal rises of plasma renin activity in both patients; however, plasma aldosterone levels increased only in the boy and not in his sister. Screening for abnormalities of the ACTH receptor gene by single strand conformation polymorphism analysis revealed no abnormality. Direct sequencing of the entire coding area of the ACTH receptor gene was also normal. CONCLUSION: The syndrome of familial ACTH unresponsiveness can vary clinically and biologically within the same family.(ABSTRACT TRUNCATED AT 250 WORDS)

Twin study of the 24-h cortisol profile: evidence for genetic control of the human circadian clock.

To determine whether genetic factors control the expression of human circadian rhythmicity, we analyzed the 24-h profile of plasma cortisol in 11 monozygotic and 10 dizygotic pairs of normal male twins. Blood was sampled every 15 min, and sleep was monitored. Circadian rhythmicity was characterized by measures of amplitude, phase, and overall waveshape. Pulsatility was quantified by pulse frequency, pulse amplitude, and relative contribution of pulsatile vs. circadian variations. Data were analyzed by a procedure specifically developed for twin studies. Genetic control was demonstrated for the timing of the nocturnal nadir and for the proportion of overall temporal variability associated with pulsatility. Environmental effects were detected for the 24-h mean and the timing of the morning acrophase. The timing of the cortisol nadir is a robust marker of human circadian phase and is dependent, under entrained conditions, on the length of the endogenous period. Animal studies have shown that the endogenous period and the pattern of entrainment to exogenous 24-h periodicities are genetically controlled. Our results indicate that, despite the increased impact of social inputs, genetic factors also control human circadian rhythmicity.

Erythrocyte metabolic alterations in type I diabetes: relationship to metabolic control.

Erythrocytes from young type I diabetic patients (n = 11), incubated in their plasma in anaerobic conditions, exhibited higher glucose consumption than cells from controls (n = 11). This increased metabolic activity is believed to reflect erythrocyte alterations dependent on the degree of metabolic control, as glucose consumption was significantly correlated to glycosylated haemoglobin (HbA1) and to glucose levels (P < 0.05 and P < 0.01 respectively). Red cell hexokinase (HK) and pyruvate kinase (PK) activities were similar in both groups whereas phosphofructokinase (PFK) activity was slightly higher in patients' cells (P < 0.05). No difference was found between patients and controls for red cell ATP and 2.3 diphosphoglycerate (2.3 DPG) levels. However, the concentrations of these glycolytic products seem also closely related to the glucose homeostasis in diabetes. Indeed, within the diabetic group, ATP levels showed a negative relationship with glucose level (P < 0.05) and 2.3 DPG a positive relationship with HbA1 (P < 0.05). In conclusion, higher glycolytic activity is present in young diabetic red cells. This activity as well as ATP and 2.3 DPG levels are related to the degree of short- or long-term diabetic control. These findings stress the importance of a careful metabolic control to avoid haematological disturbances.

Dexamethasone bovine pharmacokinetics.

Dexamethasone phosphate (DXM-PHO) is an ester which is quickly hydrolysed by the bovine and the dexamethasone (DXM) plasma half-life was 5.16 h. It has been demonstrated that 54 h after DXM-PHO injection, DXM concentrations were lower than 0.1 mg/ml. Tritiated dexamethasone was also administered twice to an another young bull for metabolite investigation. The elapsed time required to recover, in plasma, half of the radioactivity injected was 8.8 h. Radioactivity recovery in the urine reached 36.4% and 22.6% for the first and the second injections respectively.

Choice of parameter for expressing bone mineralization.

In this cross-sectional study, the relative importance of anthropometric factors and that of biological parameters on bone mineralization were evaluated and their practical implications inferred on the choice of the parameter to be used for the estimation of bone mineralization. A close relationship between anthropometric factors and bone mineral content (BMC) was observed and this relationship was shown to be independent of age. Furthermore, by regression analyses, anthropometric parameters appeared to explain a large part of the variance in BMC and preceded the hormonal parameters in the stepwise analysis of this model. Using bone mineral density (BMD) data, however, we observed a weaker relationship between anthropometric factors and bone mineralization and a relatively stronger relationship between steroid hormones and bone mineralization than those observed using the BMC data. Furthermore, by multiple regression analysis the hormonal factors preceded the anthropometric parameters in the stepwise analysis of the model. As strong epidemiological and clinical evidence exists on the relationship between steroid hormones and bone loss, these results constitute a supplementary argument for the use of BMD for the estimation of bone mineralization.

Nocturnal elevation of glucose levels during fasting in noninsulin-dependent diabetes.

To define the spontaneous diurnal variations in glucose regulation during fasting in noninsulin-dependent diabetes (NIDDM), we measured circulating levels of glucose, insulin, C-peptide, GH, cortisol, and glucagon at 15-min intervals in 11 patients with untreated diabetes and 7 matched control subjects studied during a 24-h period. The rates of insulin secretion were derived from the concentrations of C-peptide by deconvolution using a two-compartment mathematical model for C-peptide distribution and metabolism. In both groups of subjects, despite continued fasting, glucose levels stopped declining in the evening and subsequently rose throughout the night to reach a morning maximum. Elevated levels persisted until noon. The morning glucose maximum corresponded to a relative increase of 23.8 +/- 5.5% above the evening nadir in NIDDM patients and 13.2 +/- 4.6% in nondiabetic subjects (P less than 0.05). In NIDDM patients, insulin levels and insulin secretion rates did not parallel the nocturnal glucose changes. In contrast, in control subjects, this nocturnal glucose rise coincided with a similar increase in insulin secretion rates. Cortisol concentrations in patients with NIDDM were higher than those in control subjects throughout the study period (P less than 0.001) and rose earlier in the evening than in control subjects, thus failing to demonstrate the normal nocturnal suppression. In both groups of subjects, the nighttime glucose elevation was temporally and quantitatively correlated with the circadian cortisol rise. GH secretion was increased in the evening and nighttime periods compared to the daytime values, and in NIDDM patients, but not in control subjects, the size of the morning glucose elevation was directly related to the magnitude of this increase in GH secretion (r = 0.88; P less than 0.01). Glucagon concentrations were similar in both groups of subjects and remained essentially constant throughout the study period. We hypothesize that the nocturnal glucose rise that occurs during fasting represents a normal diurnal variation in the set-point of glucose regulation amplified by counterregulatory mechanisms activated by the fasting condition.

Stabilisation of plasma substrate concentrations: A model for conducting metabolic studies.

Metabolic studies involving changes in plasma substrate concentrations are frequently carried out after an overnight fast. This condition, however, is a transition between the post-prandial period and the beginning of starvation, and thus is associated with rapid changes in the plasma concentration of many substrates. Such alterations might interfere with the interpretation of modifications in plasma concentrations resulting from experimental manipulations. Infusion of glucose at a rate of 250 mg kg(-1) h(-1) for 1h and subsequently at 162 mg kg(-1) h(-1) together with amino-acids at 50 mg kg(-1) h(-1) is used to stabilise the plasma concentration of most substrates within 3 h, a condition which is maintained for the subsequent 5 h or more. This study offers a model which is more suitable for many metabolic investigations than overnight fasting and which takes little time or expense to prepare.

Age, steroids and bone mineral content.

The possible existence of correlations between bone mineral content (BMC), age and serum levels of steroid hormones was investigated. It was found that dehydroepiandrosterone sulphate (DHEA-S), oestradiol (E2) and delta-4-androstenedione (A) were correlated with BMC, whereas oestrone (E1) and testosterone (T) were not. Partial correlations after adjustment for age were significant (P less than 0.05) only between E2 and DHEA-S and BMC at the L2-L4 lumbar site (BMC-1) and between DHEA-S (P less than 0.01) and BMC at the midradius site (BMC-r). Stepwise multiple regression analysis showed that, apart from age, E2 was the only factor to fit (P less than 0.05) into the mathematical model with BMC-1 as the dependent variable, while DHEA-S was the only factor to fit (P less than 0.01) with BMC-r as the dependent variable. These data suggest that different hormonal influences are related to BMC at different sites, namely E2 to lumbar trabecular bone (L2-L4) and DHEA-S to cortical bone (midradius).

Effects of the short-acting benzodiazepine triazolam, taken at bedtime, on circadian and sleep-related hormonal profiles in normal men.

Studies in rodents have shown that triazolam, a commonly used hypnotic, may shift circadian rhythms, with the direction and magnitude of the phase-shifts being dependent on the time of drug administration. To determine whether benzodiazepine, taken at standard bedtime, modifies the amount and/or temporal organization of hormonal secretion, six normal men were studied during basal conditions and on the first and third days of treatment with 0.5 mg triazolam. In each study, sleep was polygraphically monitored and plasma cortisol, growth hormone (GH), melatonin, and prolactin (PRL) (i.e., hormones influenced by circadian rhythmicity and/or sleep) were measured at 20-min intervals for 24 h. The sleep latency and the number and duration of awakenings were reduced during triazolam treatment as compared to baseline conditions. The only alteration of sleep architecture was a partial suppression of stages III + IV (SW) in late sleep. Triazolam did not affect the mean cortisol and melatonin levels or the total amount of GH secreted over the 24-h span. The circadian timings of the onsets of cortisol and melatonin secretions were essentially unaltered. The nocturnal rise of melatonin was prolonged by 45 to 60 minutes. Sleep-associated GH release was not modified by triazolam. Sleep-associated PRL secretion persisted, but in half of the nights studied was enhanced almost threefold. This effect of the drug on nocturnal PRL secretion was not specific to either the first or the third night of treatment, nor was it specific to certain subjects. Irrespective of the magnitude of the nocturnal elevation, morning PRL levels were slightly but consistently higher after triazolam treatment than under basal conditions. Normal PRL levels resumed around noon. In conclusion, administration of 0.5 mg triazolam at normal bedtime (2230) for three consecutive days may induce a transient hyperprolactinemia, but does not abolish sleep-related hormone secretion and does not affect the timing of endocrine events controlled by the circadian clock. These findings are consistent with studies in hamsters where treatment with triazolam in the early subjective night was also without effect on the rodent circadian clock.

Pseudohypoaldosteronism in eight families: different forms of inheritance are evidence for various genetic defects.

Pseudohypoaldosteronism is a rare hereditary disorder presenting in early infancy with renal salt loss leading to hyponatremia and hyperkalemia despite high levels of plasma aldosterone. The patients are insensitive to mineralocorticoids; however, sodium supplementation is able to correct electrolyte abnormalities. Absent or greatly diminished type I aldosterone receptors in peripheral mononuclear leucocytes have been recently demonstrated and explain the lack of response to mineralocorticoids. We have studied the mode of inheritance in eight families with a total of nine patients. There was evidence for an autosomal recessive form of inheritance in four families, while the other four families appeared to have an autosomal dominant mode of transmission. In three families the autosomal recessive form was characterized by normal receptor as well as hormone data in both parents, while in one family receptor levels in both parents were greatly reduced, but hormone levels were normal. In the four families with an autosomal dominant mode of transmission there was always one parent with reduced receptor binding in peripheral mononuclear leucocytes and elevated serum hormone levels. These parents were entirely asymptomatic. In an extended family we were able to study an aunt and her newborn daughter, who were both also biochemically affected but clinically asymptomatic. It, therefore, appears that this dual pattern of genetic transmission may indicate differing genetic defects which cause the same clinical picture of pseudohypoaldosteronism.

Effect of short term fasting on glucose tolerance and insulin secretion: influence of the initial glucose level.

To evaluate the effect of fasting on glucose tolerance (GT) and insulin secretion, a 5 h oral glucose tolerance test was performed after an overnight fast and after 3-6 days of fasting in 66 obese subjects presenting a normal (n = 22), impaired (n = 23) or diabetic (n = 21) GT. Insulin secretory capacity was assessed using two glucose-independent parameters of beta cell function. In the normal group, fasting induced a fall in basal glycemia from 84 +/- 1 to 58 +/- 2 mg/dl (P less than 0.001) and an increase in the area of glucose (+58 +/- 8%, P less than 0.001), insulin (+75 +/- 10%; P less than 0.001) and C-peptide (+58 +/- 10%; P less than 0.001) during OGTT, these responses were consistent with the emergence of insulin resistance. The insulin secretory capacity was significantly decreased. In the diabetic group, fasting was associated with an increase in insulin (+34 +/- 10%; P less than 0.005) and C-peptide (+34 +/- 8%; P less than 0.001) responses to OGTT despite a reduction in basal glycemia from 174 +/- 11 to 86 +/- 4 mg/dl (P less than 0.001) and in glucose response (-20 +/- 3%; P less than 0.001), indicating an improvement of insulin secretory capacity. In the group with impaired GT, basal glycemia decreased from 97 +/- 2 to 70 +/- 2 mg/dl (P less than 0.001) but glucose, insulin and C-peptide curves were not significantly affected by fasting.(ABSTRACT TRUNCATED AT 250 WORDS)

Transfer from purified porcine insulins to semisynthetic human insulins decreases insulin antibodies and circulating immune complexes in diabetic children and adolescents. A two-year follow-up.

In this long-term prospective study, including 45 diabetic children and adolescents under the age of 20 years, insulin antibodies and other immunological factors (circulating immune complexes, autoantibodies, etc.) were compared before and during a two-year follow-up after a switch-over from monocomponent porcine insulins to monocomponent semisynthetic human insulins. IgG insulin antibodies were detected in 21 children out of 45 (47%) at a mean level of 0.96 mU/ml (0.77-1.15). A significant and important decrease of both the number of patients having insulin antibodies and the level of insulin antibodies was observed 18 months after the switch-over. After 24 months, IgG insulin antibodies were only present in 5 patients (11%) at a mean level reduced by half (0.53 mU/ml; p less than 0.05). Four patients out of the five (80%) had HLA-DR3 DR4 antigens while this phenotype was only prevalent in 26% of the initial patient cohort. On the other hand, 3 months after the transfer, there was a significant and persistent decrease (by half) of non-specific immune complexes (39% of the patients with porcine insulins) which did not appear to correlate with the level of insulin antibodies. The prevalence of autoantibodies and of antinuclear factors showed no significant variations. The practical implication of these findings is that the use of semisynthetic human insulins could be of interest in patients previously treated by porcine insulins.

Osteocalcin and bone mineral content in rheumatoid arthritis.

Abnormal bone metabolism was reported in rheumatoid arthritis (RA). In order to evaluate the interest of serum osteocalcin, also called bone GLA-protein (BGP), to assess bone metabolism in RA, we studied 20 postmenopausal RA out-patients and 20 matched controls. Nine patients were treated with low-dose corticosteroids (C+) for at least one year (less than 10 mg/day, prednisolone equivalent), the remaining 11 (C-) received non-steroidal anti-inflammatory drugs (NSAID). The distal and proximal forearm bone mineral content (BMC) was measured by single photon absorptiometry, the vertebral BMC was measured by dual photon absorptiometry. A trend to low BGP was observed in the C+ group. The lowest values were observed in patients with vertebral fractures. Compared with controls, both RA groups had similar low significant BMC at the forearm sites. At the vertebral sites, the bone mineral content decrease observed in the two groups, was more marked in the C+ group. From our results, BGP did not appear as a useful index of osteoporosis in RA, except in some patients with vertebral fractures, treated with low-dose corticosteroids.

Serum osteocalcin in the assessment of corticosteroid induced osteoporosis. Effect of long and short term corticosteroid treatment.

Serum osteocalcin was measured in patients receiving corticosteroid for long and short term at different doses. Low osteocalcin levels were observed in treated patients compared to age and sex matched controls (p less than 0.001). The effect was dose dependent and paralleled the adrenal inhibition assessed by morning cortisol. Short term administration resulted in a rapid decline of baseline osteocalcin which was maintained during the treatment period and was reversible after withdrawal. Osteocalcin appeared as a sensitive index of the inhibitory effect of corticosteroid on osteoblasts.

Specific determination of plasma dexamethasone by HPLC and RIA--application to standard dexamethasone suppression test in psychiatric patients.

Three radioimmunoassays (RIA), with or without preparative HPLC, were applied to the monitoring of plasma dexamethasone (DXM) levels during standard dexamethasone suppression test (DST) in psychiatric patients. Due to the robotic ease of the fully automated HPLC process, precision of the chromatographic assay was equivalent to that of the direct assays, but prepurification improved both sensitivity and specificity. These improvements allowed the elucidation of the following features: (1) half (36) of the patients (68) displayed infranormal DXM levels (less than or equal to 0.40 ng/ml) whatever the cortisol response; (2) 22% (15) patients (68) with DXM levels in the low control range showed a strong inhibition of cortisol suppression. These observations raise some doubts on the validity of the DST test and introduce the following questions. (1) What is the dependence of cortisol suppression upon DXM absorption and catabolism? (2) Does plasma DXM measurement several hours after its physiological action still reflect its effect on the hypothalamo-hypophyseal axis? (3) What is the reliability of DXM direct assays when measuring low DXM levels in the presence of high cortisol?

Circadian variations in plasma zinc and cortisol in man.

Circadian variations of zinc and cortisol concentrations in plasma were studied in six healthy adult men. Three of them were tested over two different 24-h periods. Results were analyzed by computerizing a best-fit curve for each 24-h profile. Plasma zinc displayed a morning peak between 8.00 and 9.00 a.m. followed by an almost linear decline throughout the day with lowest values observed shortly before 6.00 p.m. A transitory increase occurred between 6.00 p.m. and 8.00 p.m. followed by a slow decrease reaching its nadir around midnight. Thereafter zinc increased steadily until 8.00 a.m. A similar profile was observed in a seventh subject who was undergoing therapeutic starvation for obesity (fifth day of the starvation period). In all subjects the time course of plasma cortisol fluctuations paralleled that of zinc. Our results confirm the existence of a circadian rhythm in plasma zinc independent of zinc intake and temporally related to the circadian rhythm of cortisol.

Serum levels of gonadotrophins and steroid hormones in the post-menopause and later life.

Changes in the serum levels of gonadotrophins and steroid hormones with increasing age were studied in 449 women aged 40 and over to investigate the relationships between these hormones even very late in life. The levels of oestradiol (E2) and dehydroepiandrosterone sulphate (DHEA-S) fell after age 50 and remained low thereafter. However, while serum oestrone (E1), testosterone (T), delta-4-androstenedione (A) and prolactin (PRL) concentrations also decreased initially after age 50 they subsequently rose again progressively and this increase was in fact significant in the case of E1. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) rose after age 50, but whereas FSH remained elevated, LH decreased late in life. Cortisol (F) increased significantly after age 70. There was a significant correlation between androgens and E1 as well as between E2 and LH, even after age 60. Owing to the great heterogeneity of the population studied, it is not yet possible to speculate as to the physiopathological significance of these observations. It would seem, however, that the negative feedback effect of oestrogens on LH secretion remains operational very late in life.

Partial 17, 20-desmolase and 17 alpha-hydroxylase deficiencies in a 16-year-old boy.

Thirteen plasma steroids as well as ACTH, LH and FSH were measured by specific RIAs under basal and dynamic conditions in a 16-year-old boy (normal external genitalia, 46, XY karyotype) who presented slowness and unachievement of pubertal development. On the delta 4-pathway: basal levels of testosterone and dihydrotestosterone were low- with a normal ratio-, delta 4-androstenedione and 11 beta-hydroxyandrostenedione were in the low normal range. Meanwhile, 17 alpha-hydroxyprogesterone and progesterone levels were markedly elevated. On the delta 5-pathway: dehydroepiandrosterone was extremely low while 17 alpha-hydroxypregnenolone and pregnenolone were almost normal; dehydroepiandrosterone sulfate was subnormal while pregnenolone sulfate was normal. Cortisol, aldosterone were normal while ACTH was moderately increased. Basal and responsive levels of LH and FSH were markedly increased. ACTH stimulation induced a subnormal rise of cortisol and 11 beta-hydroxyandrostenedione, a low or absent rise of dehydroepiandrosterone, 17 alpha-hydroxypregnenolone, androstenedione and 17 alpha-hydroxyprogesterone contrasting with a marked rise of pregnenolone and progesterone. After hCG stimulation, responses were low for testosterone, extremely high for 17 alpha-hydroxyprogesterone with a normalisation of the 17 alpha-hydroxyprogesterone/progesterone ratio. Fluoxymesterone dramatically reduced the pathologically high basal levels of progesterone and 17 alpha hydroxyprogesterone. Dexamethasone induced only a minute decrease in the delta 4-progestagens, a marked decrease in pregnenolone, with a more than 80% reduction of 17 alpha- hydroxypregnenolone, dehydroepiandrosterone, dehydroepiandrosterone sulfate and androstenedione. These data suggest a defect involving the cytochrome P450 common to both 17 alpha-hydroxylase and 17, 20-desmolase activities.(ABSTRACT TRUNCATED AT 250 WORDS)