Treatment-related changes in serum neutrophil gelatinase-associated lipocalin (NGAL) in psoriatic arthritis: results from the PIPA cohort study.

OBJECTIVES: Obesity and psoriatic arthritis (PsA) have a complicated relationship. While weight alone does not cause PsA, it is suspected to cause worse symptoms. Neutrophil gelatinase-associated lipocalin (NGAL) is secreted through various cell types. Our objective was to assess the changes and trajectories in serum NGAL and clinical outcomes in patients with PsA during 12 months of anti-inflammatory treatment. METHOD: This exploratory prospective cohort study enrolled PsA patients initiating conventional synthetic or biological disease-modifying anti-rheumatic drugs (csDMARDs/bDMARDs). Clinical, biomarker, and patient-reported outcome measures were retrieved at baseline, and 4 and 12 months. Control groups at baseline were psoriasis (PsO) patients and apparently healthy controls. The serum NGAL concentration was quantified by a high-performance singleplex immunoassay. RESULTS: In total, 117 PsA patients started a csDMARD or bDMARD, and were compared indirectly at baseline with a cross-sectional sample of 20 PsO patients and 20 healthy controls. The trajectory in NGAL related to anti-inflammatory treatment for all included PsA patients showed an overall change of -11% from baseline to 12 months. Trajectories in NGAL for patients with PsA, divided into treatment groups, showed no clear trend in clinically significant decrease or increase following anti-inflammatory treatment. NGAL concentrations in the PsA group at baseline corresponded to the levels in the control groups. No correlation was found between changes in NGAL and changes in PsA outcomes. CONCLUSION: Based on these results, serum NGAL does not add any value as a biomarker in patients with peripheral PsA, either for disease activity or for monitoring.

Effectiveness of patient education as a stand-alone intervention for patients with chronic widespread pain and fibromyalgia: a systematic review and meta-analysis of randomized trials.

OBJECTIVE: Patient education is recommended as an integral component of the therapeutic plan for the management of chronic widespread pain (CWP) and fibromyalgia (FM). The key purpose of patient education is to increase the patient's competence to manage his or her own health requirements, encouraging self-management and a return to desired everyday activities and lifestyle. The aim of this systematic review was to evaluate the evidence for the benefits and potential harms associated with the use of patient education as a stand-alone intervention for individuals with CWP and FM through randomized controlled trials (RCTs). METHOD: On 24 November 2021 a systematic search of PubMed, MEDLINE, Embase, CENTRAL, PsycINFO, CINAHL, ClinicalTrials.gov, American College of Rheumatology, European League Against Rheumatism, and the World Health Organization International Clinical Trials Registry Platform identified 2069 studies. After full-text screening, five RCT studies were found to be eligible for the qualitative evidence synthesis. RESULTS: Patient education as a stand-alone intervention presented an improvement in patients' global assessment (standardized mean difference 0.79, 95% confidence interval 0.13 to 1.46). When comparing patient education with usual care, no intervention, or waiting list, no differences were found for functioning, level of pain, emotional distress in regard to anxiety and depression, or pain cognition. CONCLUSION: This review reveals the need for RCTs investigating patient education as a stand-alone intervention for patients with FM, measuring outcomes such as disease acceptance, health-related quality of life, enhancement of patients' knowledge of pain, pain coping skills, and evaluation of prioritized learning outcomes.

Who are likely to benefit from the Good Life with osteoArthritis in Denmark (GLAD) exercise and education program? An effect modifier analysis of a randomised controlled trial.

OBJECTIVE: To identify contextual factors that modify the treatment effect of the 'Good Life with osteoArthritis in Denmark' (GLAD) exercise and education programme compared to open-label placebo (OLP) on knee pain in individuals with knee osteoarthritis (OA). METHODS: Secondary effect modifier analysis of a randomised controlled trial. 206 participants with symptomatic and radiographic knee OA were randomised to either the 8-week GLAD programme (n = 102) or OLP given as 4 intra-articular saline injections over 8 weeks (n = 104). The primary outcome was change from baseline to week 9 in the Knee injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale (range 0 (worst) to 100 (best)). Subgroups were created based on baseline information: BMI, swollen study knee, bilateral radiographic knee OA, sports participation as a young adult, sex, median age, a priori treatment preference, regular use of analgesics (NSAIDs or paracetamol), radiographic disease severity, and presence of constant or intermittent pain. RESULTS: Participants who reported use of analgesics at baseline seem to benefit from the GLAD programme over OLP (subgroup contrast: 10.3 KOOS pain points (95% CI 3.0 to 17.6)). Participants with constant pain at baseline also seem to benefit from GLAD over OLP (subgroup contrast: 10.0 points (95% CI 2.8 to 17.2)). CONCLUSIONS: These results imply that patients who take analgesics or report constant knee pain, GLAD seems to yield clinically relevant benefits on knee pain when compared to OLP. The results support a stratified recommendation of GLAD as management of knee OA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03843931. EudraCT number 2019-000809-71.

Processed meat intake and incidence of colorectal cancer: a systematic review and meta-analysis of prospective observational studies.

The objective was to use accumulated evidence to explore the association between processed meat intake and risk of colorectal cancer (CRC) and to investigate the reliability of associations by evaluating patterns of risk by study population characteristics and research quality parameters. We included 29 observational prospective cohort studies with relative risk estimates and 95% confidence intervals for CRC according to various levels of processed meat consumption. Risk of bias was assessed using Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I) tool. Data sources were PubMed and Embase up to January 2017. The summary relative risks for high versus low processed meat consumption and risk of CRC, colon, and rectal cancer were 1.13 (95% CI: 1.01, 1.26), 1.19 (95% CI: 1.09, 1.31), and 1.21 (95% CI: 0.98, 1.49), respectively. Similar estimates were observed for the dose-response analyses. Heterogeneity across studies was detected in most analytical models. The overall judgment showed that two out of 29 studies had a moderate risk of bias, 25 had a serious risk of bias, and 2 had a critical risk of bias. The bias domains most often rated critical were bias due to risk of confounding, bias due to missing data, and selective outcome reporting bias. Although this meta-analysis indicates a modest association between processed meat intake and an increased risk of CRC, our assessment of internal validity warrants a cautious interpretation of these results, as most of the included studies were judged to have serious or critical risks of bias.

Inter-rater agreement and reliability of outcome measurement instruments and staging systems used in hidradenitis suppurativa.

BACKGROUND: Monitoring disease activity over time is a prerequisite for clinical practice and research. Valid and reliable outcome measurement instruments (OMIs) and staging systems provide researchers and clinicians with benchmark tools to assess the primary and secondary outcomes of interventional trials and to guide treatment selection properly. OBJECTIVES: To investigate inter-rater reliability and agreement in instruments currently used in hidradenitis suppurativa (HS), with dermatologists experienced in HS as the rater population of interest. METHODS: In a prospective completely balanced design, 24 patients with HS underwent a physical examination by 12 raters (288 assessments) using nine instruments. The results were analysed using generalized linear mixed models. RESULTS: For the staging systems, the study found good inter-rater reliability for Hurley staging in the axillae and gluteal region, moderate inter-rater reliability for Hurley staging in the groin and for Physician's Global Assessment, and fair inter-rater reliability for refined Hurley staging and the International HS Severity Scoring System. For all the tested OMIs, the observed intervals for limits of agreement were very wide relative to the ranges of the scales. CONCLUSIONS: The very wide intervals for limits of agreement imply that substantial changes are needed in clinical research in order to rule out measurement error. The results illustrate a difficulty, even for experienced HS experts, to agree on the type and number of lesions when evaluating disease severity. The apparent caveats call for global efforts, such as the HIdradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC) to reach consensus on how best to measure physical signs of HS reliably in randomized trials. What's already known about this topic? Without valid and reliable instruments to measure outcomes, researchers and clinicians lack the necessary benchmarks to assess primary and secondary end points of interventional trials properly. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. Several outcome measure instruments exist for HS, but their validation is generally incomplete or of relatively low methodological quality. What does this study add? Using a prospective completely balanced design this study examined inter-rater reliability with HS-experienced dermatologists as the rater population of interest. The study did not find very good reliability for any included instrument or lesion counts. This study illustrates the difficulty in finding agreement on the type and number of HS lesions, even among experts. The results question whether physical signs are best measured by a traditional physician lesion count instrument. What are the clinical implications of this work? For staging, Hurley staging and physician global visual analogue scale proved to be acceptable instruments in terms of inter-rater reliability. For the instruments designed to measure changes in health status, our study illustrates how difficult it is, even for experts, to measure the physical signs of HS using a simple rater counting. Consequently, other assessment methods of physicals signs, such as ultrasound evaluation, require consideration.

Poor replicability of recommended exercise interventions for knee osteoarthritis: a descriptive analysis of evidence informing current guidelines and recommendations.

OBJECTIVE: To examine the reporting completeness of exercise-based interventions for knee osteoarthritis (OA) in studies that form the basis of current clinical guidelines, and examine if the clinical benefit (pain and disability) from exercise is associated with the intervention reporting completeness. DESIGN: Review of clinical OA guidelines METHODS: We searched MEDLINE and EMBASE for guidelines published between 2006 and 2016 including recommendations about exercise for knee OA. The studies used to inform a recommendation were reviewed for exercise reporting completeness. Reporting completeness was evaluated using a 12-item checklist; a combination of the Template for Intervention Description and Replication (TIDieR) and Consensus on Exercise Reporting Template (CERT). Each item was scored 'YES' or 'NO' and summarized as a proportion of interventions with complete descriptions and each intervention's completeness was summarized as the percentage of completely described items. The association between intervention description completeness score and clinical benefits was analyzed with a multilevel meta-regression. RESULTS: From 10 clinical guidelines, we identified 103 original studies of which 100 were retrievable (including 133 interventions with 6,926 patients). No interventions were completely described on all 12 items (median 33% of items complete; range 17-75%). The meta-regression analysis indicated that poorer reporting was associated with greater effects on pain and no association with effects on disability. CONCLUSION: The inadequate description of recommended interventions for knee OA is a serious problem that precludes replication of effective interventions in clinical practice. By consequence, the relevance and usability of clinical guideline documents and original study reports are diminished. PROSPERO: CRD42016039742.

A core domain set for hidradenitis suppurativa trial outcomes: an international Delphi process.

BACKGROUND: There is no consensus on core outcome domains for hidradenitis suppurativa (HS). Heterogeneous outcome measure instruments in clinical trials likely leads to outcome-reporting bias and limits the ability to synthesize evidence. OBJECTIVES: To achieve global multistakeholder consensus on a core outcome set (COS) of domains regarding what to measure in clinical trials for HS. METHODS: Six stakeholder groups participated in a Delphi process that included five anonymous e-Delphi rounds and four face-to-face consensus meetings to reach consensus on the final COS. The aim was for a 1 : 1 ratio of patients to healthcare professionals (HCPs). RESULTS: A total of 41 patients and 52 HCPs from 19 countries in four continents participated in the consensus process, which yielded a final COS that included five domains: pain, physical signs, HS-specific quality of life, global assessment and progression of course. A sixth domain, symptoms, was highly supported by patients and not by HCPs but is recommended for the core domain set. CONCLUSIONS: Routine adoption of the COS in future HS trials should ensure that core outcomes of importance to both patients and HCPs are collected.

Association between alcohol, cannabis, and other illicit substance abuse and risk of developing schizophrenia: a nationwide population based register study.

BACKGROUND: Several studies have examined whether use of substances can cause schizophrenia. However, due to methodological limitations in the existing literature (e.g. selection bias and lack of adjustment of co-abuse) uncertainties still remain. We aimed to investigate whether substance abuse increases the risk of developing schizophrenia, addressing some of these limitations. METHOD: The longitudinal, nationwide Danish registers were linked to establish a cohort of 3 133 968 individuals (105 178 673 person-years at risk), identifying 204 505 individuals diagnosed with substance abuse and 21 305 diagnosed with schizophrenia. Information regarding substance abuse was extracted from several registers and did not include psychotic symptoms caused by substance abuse in the definition. This resulted in a large, generalizable sample of exposed individuals. The data was analysed using Cox regression analyses, and adjusted for calendar year, gender, urbanicity, co-abuse, other psychiatric diagnosis, parental substance abuse, psychiatric history, immigration and socioeconomic status. RESULTS: A diagnosis of substance abuse increased the overall risk of developing schizophrenia [hazard ratio (HR) 6.04, 95% confidence interval (CI) 5.84-6.26]. Cannabis (HR 5.20, 95% CI 4.86-5.57) and alcohol (HR 3.38, 95% CI 3.24-3.53) presented the strongest associations. Abuse of hallucinogens (HR 1.86, 95% CI 1.43-2.41), sedatives (HR 1.68, 95% CI 1.49-1.90), and other substances (HR 2.85, 95% CI 2.58-3.15) also increased the risk significantly. The risk was found to be significant even 10-15 years subsequent to a diagnosis of substance abuse. CONCLUSION: Our results illustrate robust associations between almost any type of substance abuse and an increased risk of developing schizophrenia later in life.

Clinical features and outcome in a Danish cohort of juvenile dermatomyositis patients.

OBJECTIVES: To assess disease characteristics and outcome in Danish juvenile dermatomyositis (JDM) patients (1977-2007). METHODS: Medical record review of hospital records identified from the National Patient Register. RESULTS: Fifty-seven JDM patients were identified. Follow-up time was 7 years (range 0.06-30). Female:male ratio was 2.5:1. Mean age at disease onset was 7 years (SD±3.7), range 1.5-16.0 years. Diagnostic delay was 0.7 years (SD±1.6), range 0.04-9 years. Mean disease duration was 3.7 years (SD±3.5), range 0.7-9 years. Thirty-nine patients (70%) were in full remission. Three patients (5%) were deceased. Disease/treatment-induced damage was present in 35 (61%) patients. Decreased pulmonary function occurred early in the disease course (median 10 months), osteoporosis and calcinosis occurred later (median 18 and 22 months). Four patients developed persistent damage within the first 6 months, four developed calcinosis within the first year. Shorter disease duration was associated with less damage (p=0.004). In a multivariate assessment analysis age >10 years at disease onset was associated with more damage (p<0.01), OR 10.96 (CI 1.6-73.6), and disease duration >4 years was associated with calcinosis (p=0.01) OR 23.2 (CI 2.6-206.2). CONCLUSIONS: We present a nationwide retrospective study of Danish JDM patients from 1977-2007. Although 70% were in remission, 61% of the patients had clinical signs of damage. Only a few patients developed damage within the first year of the disease. Longer disease duration and higher age at disease onset was correlated with more disease damage.

Etiology of common childhood acute lymphoblastic leukemia: the adrenal hypothesis.

The pattern of infections in the first years of life modulates our immune system, and a low incidence of infections has been linked to an increased risk of common childhood acute lymphoblastic leukemia (ALL). We here present a new interpretation of these observations--the adrenal hypothesis--that proposes that the risk of childhood ALL is reduced when early childhood infections induce qualitative and quantitative changes in the hypothalamus-pituitary-adrenal axis that increase plasma cortisol levels. This may directly eliminate leukemic cells as well as preleukemic cells for the ALL subsets that dominate in the first 5-7 years of life and may furthermore suppress the Th1-dominated proinflammatory response to infections, and thus lower the proliferative stress on pre-existing preleukemic cells.

Epilepsy among children in Greenland.

INTRODUCTION: Epilepsy has been considered to be more frequent in Greenland than in Denmark, where the prevalence among children is 0.40%. STUDY DESIGN: Evaluation of the prevalence, diagnosis and treatment of epilepsy among children in Greenland aged 0-15 years. METHODS: During autumn 2000, 13 out of 18 hospitals in Greenland were visited. The population of children in the areas visited was 11,965 of a total of 15,226 in Greenland. All children with the diagnosis of epilepsy were referred for evaluation and the diagnosis was confirmed. When possible, informed consent was obtained to collect data from medical records. RESULTS: 43 children (18 boys) had the diagnosis of epilepsy. For 38 (15 boys) further data were obtained. Mean age was 8.5 years (3-14) for boys and 7.9 years (2-14) for girls. The age at diagnosis was 4.9 years (1-11) for boys and 4.2 years (0-10) for girls. The prevalence of epilepsy was 0.34%. In 31 cases an electroencephalograph (EEG) recording was done, comprising sleep recordings in 26 cases. Medication was according to recommendations in Denmark. CONCLUSION: The prevalence of epilepsy in children and the medical treatment of epilepsy among children in Greenland is the same as in Denmark.

Constitutive activation of tethered-peptide/corticotropin-releasing factor receptor chimeras.

Constitutive activity, or ligand-independent activity, of mutant G protein-coupled receptors (GPCRs) has been described extensively and implicated in the pathology of many diseases. Using the corticotropin-releasing factor (CRF) receptor and the thrombin receptor as a model, we present a ligand-dependent constitutive activation of a GPCR. A chimera in which the N-terminal domain of the CRF receptor is replaced by the amino-terminal 16 residues of CRF displays significant levels of constitutive activation. The activity, as measured by intracellular levels of cAMP, is blocked in a dose-dependent manner by the nonpeptide antagonist antalarmin. These results support a propinquity effect in CRF receptor activation, in which the amino-terminal portion of the CRF peptide is presented to the body of the receptor in the proper proximity for activation. This form of ligand-dependent constitutive activation may be of general applicability for the creation of constitutively activated GPCRs that are regulated by peptide ligands such as CRF. These chimeras may prove useful in analyzing mechanisms of receptor regulation and in the structural analysis of ligand activated receptors.

Electroconvulsive stimuli enhance both neuropeptide Y receptor Y1 and Y2 messenger RNA expression and levels of binding in the rat hippocampus.

Repeated electroconvulsive stimulations and other seizure modalities produce an increase in neuropeptide Y synthesis and local release in the rat hippocampus, and perhaps as a consequence, a change in the concentration of neuropeptide Y binding sites in the same region. The aim of the present study was to determine possible changes in the expression of neuropeptide Y receptor subtypes affected by repeated stimulations in the hippocampus. Rats were exposed to 14 daily stimulations, and the brains were removed 24h after the last stimulation. For in vitro receptor autoradiography and in situ hybridisation histochemistry, the brains were frozen, sectioned, and levels of neuropeptide Y binding sites and messenger RNA expressions were determined quantitatively on sections from the same animals. In order to determine the contribution of different neuropeptide Y receptor subtypes, serial sections were incubated with either 125I-labelled peptide YY alone or the same radio-labelled peptide mixed with an excess of a number of displacing compounds with affinity for either neuropeptide Y receptor subtype Y1, Y2, or both. Binding studies revealed that the majority of peptide YY binding sites was represented by Y2, and that electroconvulsive stimulations reduced the binding capacity or the concentration of this receptor. A prominent reduction of Y1-preferring binding sites was determined in the dentate gyrus, and to a lesser extent in the CA1 and CA3 regions. Similarly, the treatment produced a significant reduction of Y2-preferring binding sites in the CA1 and CA3 region, but not in the granular cell layer of the dentate gyrus. Using semi-quantitative in situ hybridization, Y1 receptor messenger RNA level in the granular cell layer of the dentate increased by the stimulations. In the same region, Y2 receptor messenger RNA was expressed in low to undetectable amounts, but after the repeated stimulations, this transcript was found in moderate to high levels. These data suggest that the neuropeptide Yergic system in the dentate gyrus and the pyramidal cell layer are affected by the treatment, and that this includes both Y1 and Y2 receptor subtypes. Because levels of messenger RNA and binding are distinctly regulated, the turnover of both Y1 and Y2 molecules is strongly increased under electroconvulsive stimulations, suggesting that the intrahippocampal neuropeptide Yergic neurotransmission is also increased under the stimulations.

Disulfide bridge engineering in the tachykinin NK1 receptor.

As in most other seven-transmembrane receptors, the central disulfide bridge from the extracellular end of TM-III to the middle of the second extracellular loop was essential for ligand binding in the NK1 receptor. However, introduction of "extra", single Cys residues in the second extracellular loop, at positions where disease-associated Cys substitutions impair receptor function in the vasopressin V2 receptor and in rhodopsin, did not cause mispairing with the Cys residues involved in this central disulfide bridge. Cys residues were introduced in the N-terminal extension and in the third extracellular loop, respectively, in such a way that disulfide bridge formation could be monitored by loss of substance P binding and breakage of the bridge could be monitored by gain of ligand binding. This disulfide bridge formed spontaneously in the whole population of receptors and could be titrated with low concentrations of reducing agent, dithiothreitol. Another putative disulfide bridge "switch" was constructed at the extracellular ends of TM-V and -VI, i.e., at positions where a high-affinity zinc site previously had been constructed with His substitutions. Disulfide bridge formation at this position, monitored by loss of binding of the nonpeptide antagonist [3H]LY303.870, occurred spontaneously only in a small fraction of the receptors. It is concluded that disulfide bridges form readily between Cys residues introduced appropriately in the N-terminal extension and the third extracellular loop, whereas they form with more difficulty between Cys residues placed at the extracellular ends of the transmembrane segments even at positions where high-affinity metal ion sites can be constructed with His residues.

[Arthritis as first symptom of leukemia in children]. / Arthritis som debutsymptom ved leukaemi hos børn.

Three children out of 30 (10%) referred for juvenile chronic arthritis had leukaemia. The patients had complained of intermittent musculoskeletal pain and painful joint swelling for three weeks, nine months and eighteen months prior to admission. On admission two of the patients had active arthritis with soft tissue swelling in one and three joints respectively. The third patient had only arthralgias and no joint swelling. All patients had slight anaemia, normal to slightly reduced thrombocyte count, slight neutropenia and absence of blasts in the peripheral blood. The correct diagnosis was made by bone marrow aspiration. Two children had acute lymphoblastic leukaemia and the third acute myeloblastic leukaemia. Leukaemia thus remains an important differential diagnosis in children presenting with musculoskeletal pain and/or arthritis.

[Randomized comparison of intravenous immunoglobulin and methylprednisolone pulse therapy in children with newly diagnosed idiopathic thrombocytic purpura. The Danish ITP Study Group]. / Randomiseret sammenligning af intravenøs immunglobulin og methylprednisolon-pulsterapi hos børn med nydiagnosticeret idiopatisk trombocytopenisk purpura. The Danish ITP Study Group.

Forty three children with newly diagnosed idiopathic thrombocytopenic purpura (ITP), platelet count (pl.c.) below 20 x 10(9)/l, and either clinically significant bleeding or failure to show a spontaneous platelet rise within three days of admission were randomly allocated to treatment with intravenous infusions of either immunoglobulin (IVIG) 1 g/kg or methylprednisolone (MPPT) 30 mg/kg on two consecutive days. Prompt induction of partial remission with pl.c. > 50 x 10(9)/l after 72 hours was seen in 21/23 given IVIG versus 10/20 given MPPT (exact p = 0.003); mean pl.c.s after 72 hours were 188 versus 77 x 10(9)/l (2p < 0.001). Poor responders were then given the alternative infusions in addition. After six days, complete remission with pl.c. > 150 x 10(9)/l was achieved in 16/23 versus 10/20 (p = 0.16). During six months follow-up, there were no significant differences regarding relapse rates or chronic course. Eleven children with relapse were crossed over to the alternative treatment arm: the estimated treatment effect in pl.c. after 72 hours was 134 x 10(9)/l in favour of IVIG. These results indicate that IVIG infusions may be preferable to high-dose corticosteroids as initial treatment for children with ITP.

Split-receptors in the tachykinin neurokinin-1 system--mutational analysis of intracellular loop 3.

Several membrane proteins have been functionally expressed from non-covalently coupled, contiguous segments especially with the split-site located between natural domains. Experiments using such 'split-proteins' were here performed in the tachykinin neurokinin-1 (NK1) receptor with co-expression of contiguous segments with split-sites positioned in various intracellular and extracellular loops. The construct where the split-site was located in intracellular loop 3 gave a reasonable expression level of substance-P-binding sites, i.e. 12% of wild-type expression. Of the other split-receptors tested, only the one with the split-site located just outside transmembrane (TM) segment-V gave any detectable substance P binding, which however only was 1% of the wild-type expression level. The construct with the split-site located in intracellular loop 3 bound all of the tested peptide agonists and non-peptide antagonists with normal affinity and was able to stimulate inositol phosphate turnover with a normal EC50 for substance P and an Emax according to the expression level. When intracellular loop 3 was either extended with 112 amino acid residues derived from the muscarine M2 receptor or, when major parts of the loop were deleted in the non-split NK1 receptor, the affinity for neither substance P nor for the prototype nonpeptide antagonist, CP96,345 was affected, yet an increase in EC50 for substance P was observed. Also in the split-receptor, most of intracellular loop 3 could be substituted or even deleted without affecting ligand affinity, although a decreased expression level was observed in constructs having major deletions. It is concluded, that the NK1 receptor is preferentially reconstituted by co-expression of a putative A-domain including TM-I-V and a B-domain including TM-VI and -VII. It is suggested that a number of rhodopsin-like 7TM receptors may function as two-domain structures based on the finding that a network of short loops has been highly conserved within each of the putative domains and, that these domains are separated by a relatively long and in respect of length poorly conserved loop, i.e. intracellular loop 3.

Neuro-acanthocytosis--a rare cause of chorea.

Neuro-acanthocytosis is a rare neurological disorder characterised by stereotyped chorea, especially of the mouth, areflexia and acanthocytes seen in the peripheral blood. No cases have been described in the literature from South Africa. We report here a case of neuro-acanthocytosis seen in a black woman who presented to Johannesburg Hospital.