Early Nutritional Follow-Up after Discharge Prevents Deterioration of ADL Functions in Malnourished, Independent, Geriatric Patients Who Live Alone - A Randomized Clinical Trial.

OBJECTIVES: To compare the effects of two nutritional follow-up interventions with regard to preventing short-term deterioration in ADL, and to compare their effects on physical function, emotional health, and health-related quality of life. DESIGN: Randomized clinical trial with two intervention groups and one control group, and a follow-up period of eight weeks. SETTING: Intervention in the participants' homes after discharge from hospital. PARTICIPANTS: Inclusion: Malnourished geriatric patients and patients at risk of malnutrition (MNA<24), aged 75 years and older, living at home and alone. Exclusion: Nursing home residents and patients with terminal illnesses or cognitive impairment. Randomization: At discharge, the patients were assigned to one of three groups: 'home visit', 'telephone consultation', or 'control' group. INTERVENTION: Individually tailored nutritional counselling of the patient and the patient's daily home carer by a clinical dietician one, two, and four weeks after discharge from hospital. The counselling was either in-person at the patients' homes, or by telephone. The control group received no follow-up after discharge. MEASUREMENTS: Primary outcome: Change in ADL (Barthel-100 score) at discharge and eight weeks later. SECONDARY OUTCOMES: Change in physical performance (handgrip strength, 30-sec. chair stand test, CAS), quality of life and depression measurements (SF-36, Depression List, Geriatric Depression Score), and Avlund mobility-tiredness score (Mob-T). RESULTS: Two-hundred and eight participants were randomized, 73 to home visits and 68 to telephone consultations. The control group comprised 67 patients. The mean age of the participants was 86.1 years. At eight weeks after discharge, 157 completed the follow-up (home visit 52, telephone consultation 51, and control group 54). The mean age of these patients was 85.8 years. More patients in the home visit group improved or maintained their ADL (96%), compared to the telephone (75%) and control groups (72%), p<0.01. No difference was detected among the groups with regard to physical measurements, health-related quality of life, and emotional health. CONCLUSION: Early nutritional follow-up after discharge, performed as home visits, prevents deterioration of ADL in malnourished, independent, geriatric patients who live alone and thereby preserves their independence.

Comparative effect of paracetamol, NSAIDs or their combination in postoperative pain management: a qualitative review.

BACKGROUND: Quantitative reviews of postoperative pain management have demonstrated that the number of patients needed to treat for one patient to achieve at least 50% pain relief (NNT) is 2.7 for ibuprofen (400 mg) and 4.6 for paracetamol (1000 mg), both compared with placebo. However, direct comparisons between paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) have not been extensively reviewed. The aims of this review are (i) to compare the analgesic and adverse effects of paracetamol with those of other NSAIDs in postoperative pain, (ii) to compare the effects of combined paracetamol and NSAID with those of either drug alone, and (iii) to discuss whether the adverse effects of NSAIDs in short-term use are justified by their analgesic effects, compared with paracetamol. METHODS: Medline (1966 to January 2001) and the Cochrane Library (January 2001) were used to perform a systematic, qualitative review of postoperative pain studies comparing paracetamol (minimum 1000 mg) with NSAID in a double-blind, randomized manner. A quantitative review was not performed as too many studies of high scientific standard (27 out of 41 valid studies, including all major surgery studies) would have been excluded. RESULTS: NSAIDs were clearly more effective in dental surgery, whereas the efficacy of NSAIDs and paracetamol seemed without substantial differences in major and orthopaedic surgery, although firm conclusions could not be made because the number of studies was limited. The addition of an NSAID to paracetamol may confer additional analgesic efficacy compared with paracetamol alone, and the limited data available also suggest that paracetamol may enhance analgesia when added to an NSAID, compared with NSAIDs alone. CONCLUSION: Paracetamol is a viable alternative to the NSAIDs, especially because of the low incidence of adverse effects, and should be the preferred choice in high-risk patients. It may be appropriate to combine paracetamol with NSAIDs, but future studies are required, especially after major surgery, with specific focus on a potential increase in side-effects from their combined use.

Effects of gabapentin in acute inflammatory pain in humans.

BACKGROUND AND OBJECTIVES: The aim of the study was to examine the analgesic effects of the anticonvulsant, gabapentin, in a validated model of acute inflammatory pain. METHODS: Twenty-two volunteers were investigated in a double-blind, randomized, placebo-controlled cross-over study. Gabapentin 1,200 mg or placebo was given on 2 separate study days. Three hours after drug administration, a first-degree burn injury was produced on the medial aspect of the nondominant calf (12.5 cm(2), 47 degrees C for 7 minutes). Quantitative sensory testing (QST) included pain ratings to thermal and mechanical stimuli (visual analog scale [VAS]), assessments of thermal and mechanical detection thresholds, and areas of secondary hyperalgesia. Side effects drowsiness and postural instability were assessed by subjective ratings (VAS). RESULTS: The burn injury induced significant primary and secondary hyperalgesia (P <.0001). Gabapentin diminished the decrease in mechanical pain threshold in the burn area (P =.04) and reduced secondary hyperalgesia, but the reduction was not significant (P =.06). Heat pain thresholds, pain during the burn, and mechanical pain in the area of secondary hyperalgesia were not significantly changed by gabapentin (P <.2). Ratings of drowsiness and unsteadiness during walking were significantly higher for gabapentin than for placebo (P <.05). CONCLUSIONS: The study indicates that gabapentin has no analgesic effect in normal skin, but may reduce primary mechanical allodynia in acute inflammation following a thermal injury. These observations suggest a clinical potential of gabapentin in the treatment of postoperative pain.

Effect of peripheral morphine in a human model of acute inflammatory pain.

Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo-controlled, three-way crossover design in a human model of acute inflammatory pain (heat injury). We studied 18 healthy volunteers who each received morphine locally (2 mg), morphine systemically (2 mg), or placebo on three separate study days. The subjects received morphine infiltration subcutaneously (s.c.). 1 h before heat injury (47 degrees C, 7 min) and naloxone infiltration s.c. (0.2 mg) 2.5 h after the heat injury. Hyperalgesia to mechanical and heat stimuli were examined using von Frey hairs and thermodes, and pain was rated using a visual analogue scale. The burns produced significant hyperalgesia, but local morphine infiltration neither reduced pain during the burn, nor primary or secondary hyperalgesia to mechanical and heat stimuli after the burn. In conclusion, peripherally applied morphine had no acute antinociceptive effects in this human model of acute inflammatory pain.

Inflammatory pain in experimental burns in man.

Human experimental pain models are important tools in pain research. The primary aims of pain research in normal man is 1) to provide insight in pain mechanisms, 2) to provide a rational basis for clinical trials of pain relieving interventions, and 3) to confirm the anti-nociceptive effects demonstrated in animal models. Most often clinical pain is due to tissue damage leading to acute inflammation and hyperalgesia, but only few human pain models have examined pain responses in injured tissues. Therefore, models with controlled and reversible tissue trauma are needed. The human burn model is an example of such a model, and several groups have performed studies of analgesics and pain mechanisms based on the model. The thesis aims to provide a critical review of the human burn model as a tool in pain research, and to give suggestions for development of the model and future research. The pain and inflammatory responses to superficial thermal burns in skin have been studied in healthy volunteers. Burns have the potential for releasing most of the inflammatory and chemical mediators that produce sensitisation and excitation of nociceptors, and the intense nociceptive input during injury produces sensitisation of central neurones in the nociceptive pathway. Pain and hyperalgesia have been evaluated in the model by thermal, various mechanical, and electrical stimuli. The different methods of pain assessments are discussed to clarify the underlying neural mechanisms, the questions that can be addressed by the measurements, and the discrepancies in results between studies. Inflammation has been evaluated in the model by skin erythema intensity, area of flare, and blister formation. The major determinant of skin erythema intensity is the amount of blood in the most superficial part of the dermis, and burn-induced erythema may be primarily due to congestion of capillary loops and postcapillary venules. The area of flare may be used to evaluate the efferent function of heat-sensitive A delta- and C-fibre nociceptors, whereas blisters may be used to assess edema formation and the degree of injury. Hyperalgesia is induced immediately by the burns and lasts about 24 h dependent on the intensity of the heat stimulus. The burns heal without sequela. A study of the reproducibility of pain assessments in the burn model has shown that measures based on repeated measurements were significantly more reproducible than measures based on single time points. Further, within-day reproducibility was better than between-day reproducibility. Within-day variations of heat pain responses to 45 degrees C and 47 degrees C were smaller than that of pain responses to 43 degrees C, suggesting that assessments using clearly painful stimuli may be more reproducible. A methodological study also demonstrated that habituation to experimental pain developed as the study proceeded. Habituation is common in experimental pain models, and dividing analgesics and placebo evenly between the study days is one way of eliminating the effects of habituation. The use of simultaneous right-left comparisons represents the ideal design when possible. The burn model has been a valuable tool in the study of pain mechanisms. Hyperalgesia to heat in the burned area (primary hyperalgesia) is mediated by sensitisation of C-fibre mechano-heat-sensitive (CMH) nociceptors and A delta-fibre mechano-heat-sensitive (AMH) nociceptors of type I in hairy skin. A contribution from sensitised CNS neurones is likely, and the sensitisation of nociceptors is confined to the injured area. The presence of hyperalgesia to heat in normal skin surrounding a burn (secondary hyperalgesia) has been demonstrated in several studies, but the pain threshold may be unaltered. The mechanisms for primary hyperalgesia to mechanical stimuli may be both peripheral and central, but the importance of peripheral mechanisms is unclear and central mechanisms may account for mechanical hyperalgesia in both the primary and th

Effect of riluzole on acute pain and hyperalgesia in humans.

Riluzole modulates several transmitter systems which may be involved in nociception. Antinociceptive effects have been shown in animal studies, but there are no human data. Therefore, we have examined the acute analgesic effect of riluzole in a human model of inflammatory pain induced by a thermal injury on the distal leg (47 degrees C, 7 min, 12.5 cm2) in 20 healthy volunteers. Hyperalgesia to mechanical and heat stimuli were examined by von Frey hairs and thermodes. We used a randomized, double-blind, placebo-controlled design, and subjects received riluzole 100 mg or placebo for 2 days with a 14-day interval. The burns produced significant hyperalgesia, but riluzole had no acute analgesic effects in normal or hyperalgesic skin.

Peripheral analgesic effects of ketamine in acute inflammatory pain.

UNLABELLED: BACKGROUND. This study examined the analgesic effect of local ketamine infiltration, compared with placebo and systemic ketamine, in a human model of inflammatory pain. METHODS: Inflammatory pain was induced by a burn (at 47 degrees C for 7 min; wound size, 2.5 x 5 cm) on the calf in 15 volunteers on 3 separate days with 7-day intervals. They received either (1) subcutaneous infiltration with ketamine in the burn area (local treatment) and contralateral placebo injections, or (2) subcutaneous ketamine contralateral to the burn (systemic treatment) and placebo in the burn area, or (3) placebo on both sides. The study was double-blinded and the order of the treatments was randomized. Hyperalgesia to mechanical and heat stimuli was examined by von Frey hairs and contact thermodes (3.75 and 12.5 cm2), and pain was rated using a visual analog scale (0-100). RESULTS: The burns produced significant hyperalgesia. Local ketamine infiltration reduced pain during the burn injury compared with systemic treatment and placebo (P < 0.01). Heat pain thresholds were increased by local ketamine treatment compared with placebo immediately after injection (P < 0.03), and so were the mechanical pain thresholds (P = 0.02). Secondary hyperalgesia and suprathreshold pain responses to heat and mechanical stimuli were not significantly affected by local ketamine. No difference between local ketamine and placebo could be detected 1 h and 2 h after the burn. CONCLUSIONS: Ketamine infiltration had brief local analgesic effects, but several measures of pain and hyperalgesia were unaffected. Therefore, a clinically relevant effect of peripheral ketamine in acute pain seems unlikely.

Hyperalgesia in a human model of acute inflammatory pain: a methodological study.

The aim of the study was to examine reproducibility of primary and secondary hyperalgesia in a psychophysical model of human inflammatory pain. Mild burns were produced on the crura of 12 volunteers with a 50 x 25 mm thermode (47 degrees C, 7 min). Assessments of (i) cold and warm detection thresholds, (ii) mechanical and heat pain thresholds, (iii) pain to heat (43 degrees C and 45 degrees C, 5 s), (iv) secondary hyperalgesia, and (v) skin erythema were made 1.75 and 0.5 h before, and 0, 1, 2, 4, and 6 h after a burn injury. Sensory thresholds and hyperalgesia to heat and mechanical stimuli were examined by contact thermodes and von Frey hairs, and pain intensity was rated with a visual analog scale (0-100). To describe between-day reproducibility, the subjects were examined three times at intervals of 21 days. Within-day comparisons showed that a 20% change could be detected as significant for all variables with fewer than 12 subjects in a cross-over design (2alpha = 5% and power = 80%). Between-day comparisons demanded up to 25 subjects to detect changes of the same magnitude. The burns caused mild to moderate pain (VAS: mean 29, SD 14) and the subjects (all right-handed) were more sensitive to heat pain on their left side (P < 0.03). Hyperalgesia was induced instantaneously by the burn and outlasted the study period (6 h). However, no spontaneous pain was observed after the injury, and a brief period of hypoesthesia to warm and cold stimuli was induced by the burn. The painful measurements themselves evoked hyperalgesia to heat and mechanical stimuli on the arm, but only to mechanical stimuli on the legs. including secondary hyperalgesia. Hyperalgesia evoked by the measurements was significantly less intense than that induced by injury. Habituation to the painful stimuli was demonstrated by significantly higher pain thresholds and lower pain responses on the second and third day of the study. The burn model is a sensitive psychophysical model of acute inflammatory pain, when cross-over designs and within-day comparisons are used, and the model is suitable for double-blind, placebo-controlled studies of analgesics. In similar models, we recommend that analgesic and placebo are evenly divided between right and left sides and study days.

Hyperalgesia and temporal summation of pain after heat injury in man.

Temporal summation of pain occurs when repeated stimuli become increasingly painful in spite of unchanged stimulus intensity. Summation can be quantified as the difference in pain between the first and the last stimulus in a train of stimuli. The aim of the study was to compare temporal summation of pain in normal skin with summation of pain in skin with primary and secondary hyperalgesia evoked by a heat injury. A heat injury was produced on the crus of 12 volunteers with a 50 x 25 mm thermode (47 degrees C, 7 min). Measurements were made before, and 0, 1, 2, and 4 h after the heat injury, in three areas: primary and secondary mechanical hyperalgesia induced by the heat injury, and in a mirror image of the injury on the opposite leg. Temporal summation of pain was induced by repeated electrical stimuli (five stimuli at 2 Hz) and assessed by visual analog scale (VAS). Primary hyperalgesia was evaluated by von Frey hairs and electrical stimuli, and the areas of secondary hyperalgesia with a rigid von Frey hair (314 mN). Significant primary (P < 0.000001) and secondary (P < 0.00006) mechanical hyperalgesia were evoked by the heat injury. The pain threshold to single electrical stimuli was reduced within the injury (P < 0.03), but not outside. The pain responses to single and repeated electrical stimuli were not significantly altered by the injury. Temporal summation of pain occurred in 418 stimulus trains out of 576 (73%), but no significant changes in summation developed in skin with primary or secondary mechanical hyperalgesia compared with normal skin (baseline measurements). Temporal summation at high stimulus intensities was more pronounced than at lower intensities (P < 0.0002). We found no correlation between either temporal summation and area of secondary hyperalgesia, or temporal summation and pain intensity during the induction of heat injury. We conclude that the development of primary and secondary mechanical hyperalgesia after heat injury in man was not associated with changes in temporal summation of painful electrical stimuli.

Effect of sympathetic nerve block on acute inflammatory pain and hyperalgesia.

BACKGROUND: Sympathetic nerve blocks relieve pain in certain chronic pain states, but the role of the sympathetic pathways in acute pain is unclear. Thus the authors wanted to determine whether a sympathetic block could reduce acute pain and hyperalgesia after a heat injury in healthy volunteers. METHODS: The study was made as a randomized, single blinded investigation, in which the volunteers served as their own controls. A lumbar sympathetic nerve block and a contralateral placebo block were performed in 24 persons by injecting 10 ml bupivacaine (0.5%) and 10 ml saline, respectively. The duration and quality of blocks were evaluated by the sympatogalvanic skin response and skin temperature. Bilateral heat injuries were produced on the medial surfaces of the calves with a 50 x 25 mm thermode (47 degrees C, 7 min) 45 min after the blocks. Pain intensity induced by heat, pain thresholds to thermal and mechanical stimulation, and secondary hyperalgesia were assessed before block, after block, and 1, 2, 4, and 6 h after the heat injuries. RESULTS: Of the 24 volunteers, eight were excluded because of somatic block or incomplete sympathetic block. The study revealed no significant differences between sympathetic block and placebo for pain or mechanical allodynia during injury, or pain thresholds, pain responses to heat, or areas of secondary hyperalgesia after the injury. The comparisons were done for the period when the block was effective. CONCLUSION: Sympathetic nerve block did not change acute inflammatory pain or hyperalgesia after a heat injury in human skin.

[The acute inflammatory response. Mechanisms and therapeutic possibilities]. / Det akutte inflammatoriske respons. Mekanismer og behandlingsmuligheder.

The paper reviews the events and mechanisms of the inflammatory response and the possibilities of modulation. The functions of several important inflammatory mediators and possible therapy related to these are summarized. The paper further describes the major events of the inflammatory response, primary and secondary mediators, the cellular origin of the mediators and possible regulatory mechanisms of the inflammatory response. The causes of inflammatory dysregulation are not clear in most cases and control of the inflammatory response will be improved, when the timing of and the relations between the mediators are clarified. Management of the dysregulated or autonomous inflammatory response may go beyond inhibition of mediators and include active support of depleted mediators. Interventions should start early in the acute process and be multimodal. Treatment of pain related to inflammatory conditions may be improved by more specific interventions at the level of the nociceptors.

Analgesic and anti-inflammatory effects of lignocaine-prilocaine (EMLA) cream in human burn injury.

Pain relief may be improved by reducing sensitization of nociceptive pathways caused by tissue injury. Such a reduction depends mainly on inhibition of local inflammatory changes and the relation between duration of nociceptive block and nociceptive input. In this study we examined if prolonged topical treatment with local anaesthetics could reduce late hyperalgesia and local inflammation after burn injury in healthy volunteers. The effects of EMLA treatment for 8 h after burn on hyperalgesia, inflammation and wound healing were compared with the contralateral placebo-treated leg for 48 h after bilateral burn injuries (15 x 25 mm, 49 degrees C for 5 min) in a double-blind, randomized study in 12 healthy volunteers. Wound healing was studied 1 and 2 weeks after injury. Neither mechanical nor thermal primary hyperalgesia were affected significantly by prolonged EMLA treatment. Secondary hyperalgesia and skin erythema were also not changed. Seven of 12 placebo-treated legs developed blisters, in contrast with four of 12 EMLA-treated legs. Wound healing showed no apparent differences. Our data suggest that prolonged, topical treatment with local anaesthetics did not reduce local inflammation and late hyperalgesia.

Effect of preemptive nerve block on inflammation and hyperalgesia after human thermal injury.

BACKGROUND: Postoperative pain relief may be improved by reducing sensitization of nociceptive pathways caused by surgical trauma. Such a reduction may depend on the timing and efficacy of analgesia and the duration of the nociceptive block versus the duration of the nociceptive input. We examined whether a prolonged nerve block administered before a superficial burn injury could reduce local inflammation and late hyperalgesia after recovery from the block. METHODS: The effects of a preemptive saphenous nerve block on primary and secondary hyperalgesia, skin erythema, and blister formation, were compared to the opposite unblocked leg for 12 h after bilateral thermal injuries (15 x 25 mm, 49 degrees C for 5 min) in 20 healthy volunteers. Recovery from the block was identified by return of sensation to cold. RESULTS: Six subjects were excluded because of insufficient initial block (2 subjects) or because the block lasted beyond the study period (4 subjects). The remaining 14 subjects experienced significantly reduced primary (P = 0.005) and secondary hyperplasia (P = 0.01) in the blocked leg after return of cold sensation compared to the unblocked leg. Erythema intensity and blister formation were not significantly affected by the blockade (P = 0.94 and P = 0.07, respectively). CONCLUSIONS: These data suggest that a prolonged, preemptive nerve block reduced late hyperalgesia after thermal injury, whereas the erythema and blister formation were not significantly affected.

Topical ketorolac has no antinociceptive or anti-inflammatory effect in thermal injury.

This study investigated the antinociceptive and anti-inflammatory effect of a topical non-steroidal anti-inflammatory drug in human thermal injury. Twelve healthy unmedicated volunteers had identical burn injuries produced on the medial side of both calves with a 49 degrees C 15 x 25 mm thermode. Ketorolac gel or placebo were randomly applied on the right or left calf 1.5 h before burn injury, immediately after burn injury and 6 and 12 h later in a double-blind trial where every subject served as his own control. Heat pain detection thresholds (HPDT), head pain tolerance (HPT), mechanical pain detection thresholds (MPDT) and the intensity of burn-induced erythema (erythema index, EI) were assessed in the area of the thermal injury, and areas of hyperalgesia to pin prick were determined outside the injury before and 3, 6 and 24 h after the burn injury. Burn injury led to a decrease in HPDT, HPT and MPDT, an increase in EI and development of mechanical hyperalgesia (P < 0.05). Ketorolac gel had no effect on any of the nociceptive or inflammatory variables studies (P > 0.2).

Spermaturia in two normal boys without other signs of puberty.

We report spermaturia in two normal boys with testicular volumes of 3 ml and no other signs of puberty. This supports the hypothesis that spermatogenesis can begin before any other signs of puberty and indicates that the definition of start of puberty as testicular volumes of 4 ml or more may be too rigorous.

Topical glucocorticoid has no antinociceptive or anti-inflammatory effect in thermal injury.

We have studied the antinociceptive and anti-inflammatory effects of topical glucocorticoids in human thermal injury. The right and left legs of 12 healthy volunteers were allocated randomly to be treated with either 0.05% clobetasol propionate cream or placebo in a double-blind trial. Thermal injuries were induced with a thermode, which was heated to 49 degrees C for 5 min under standardized pressure. Clobetasol propionate or placebo cream was applied to the skin 1 h before burn injury, immediately after the injury and every 12 h for the next 3 days. Heat pain detection thresholds (HPDT), heat pain tolerance (HPT), mechanical pain detection thresholds (MPDT) and the intensity of burn-induced erythema (erythema index, EI) were assessed inside the thermal injury and areas of hyperalgesia to pinprick outside the injury were determined before and regularly for 72 h after the burn injury. Burn injury caused a decrease in HPDT, HPT and MPDT, an increase in EI and development of mechanical, secondary hyperalgesia. Clobetasol propionate had no effect on any of the nociceptive or inflammatory variables studied.

Spermaturia and puberty.

The pattern of spermaturia in boys at different stages of puberty was investigated. Fractionated 24 hour urine was collected for nine consecutive days from eight boys aged 13-14 years and 10 boys aged 15-17 years. Spermatozoa were detected by microscopic examination of the sediment. Sex characteristics were recorded. Fifty five per cent of all urine samples were positive for sperm and all boys showed spermaturia. A large variation in spermaturia was found between and within boys at the same stage of puberty. Spermaturia was a more common and regular event during early and mid-puberty than in more mature subjects. This indicates that the mechanism of spermaturia in early and late puberty could be different. It is suggested that spermaturia in non-virilised boys could be a result of a spontaneous, continuous flow of spermatozoa to the urethra in contrast with the peristaltic flow during ejaculation occurring at a later stage of puberty.

[Torsades de pointes ventricular tachycardia caused by terodiline (Mictrol)?]. / Torsades de pointes ventrikulaer takykardi udløst af terodilin (Mictrol)?

We report a 84 year old man taking terodiline who had torsades de pointes ventricular tachycardia with prolongation of the QT-interval. The QT-interval became normal after withdrawal of terodiline. Worldwide, the manufacturers have received a total of 37 reports of ventricular tachyarrhythmia during the past months, 28 of which were torsades de pointes ventricular tachycardia and have decided to recall the product temporarily.

Resolution and binding site determination of D,L-thyronine by high-performance liquid chromatography using immobilized albumin as chiral stationary phase. Determination of the optical purity of thyroxine in tablets.

Human and bovine serum albumin bound to silica or aminopropyl silica were used as chiral stationary phases (CSPs). D,L-Thyronine, D,L-tryptophan, N-benzoyl-D,L-phenylalanine, D,L-warfarin and D,L-benzoin could be resolved on these CSPs using a mobile phase of 0.05 M phosphate buffer, pH 7.0. The capacity factor of D-thyronine was higher than that of L-thyronine. The resolution of D,L-thyronine was completely lost by the presence of bilirubin in the mobile phase, but only little affected by caprylate. By contrast, the resolution of D,L-tryptophan was not affected by bilirubin, but lost by the presence of caprylate. These results are consistent with binding of D-thyronine to the bilirubin binding site and L-tryptophan to the caprylate binding site in albumin, respectively, and suggests that such "displacement chromatography" can be used for the determination of binding sites. The optical purity of D-thyroxine in tablets was determined indirectly after de-iodination by catalytic hydrogenation.