Test–re-test reliability of DSM-IV adopted criteria for 3,4-methylenedioxymethamphetamine (MDMA) abuse and dependence: a cross-national study

Aims This study evaluated the prevalence and reliability of DSM‐IV adopted criteria for 3,4‐methylenedioxymethamphetamine (MDMA) abuse and dependence with a purpose to determine whether it is best conceptualized within the category of hallucinogens, amphetamines or its own category. Design Test–re‐test study. Participants MDMA users (life‐time use >5 times) were recruited in St Louis, Miami and Sydney (n = 593). The median life‐time MDMA consumption was 50 pills at the baseline. Measurements The computerized Substance Abuse Module for Club Drug (CD‐SAM) was used to assess MDMA abuse and dependence. The Discrepancy Interview Protocol (DIP) was used to determine the reasons for the discrepant responses between the two interviews. Reliability of diagnoses, individual diagnostic criteria and withdrawal symptoms was examined using the kappa coefficient (κ). Findings For baseline data, 15% and 59% met MDMA abuse and dependence, respectively. Substantial test–re‐test reliability of the diagnoses was observed consistently across cities (κ = 0.69). ‘Continued use despite knowledge of physical/psychological problems’ (87%) and ‘withdrawal’ (68%) were the two most prevalent dependence criteria. ‘Physically hazardous use’ was the most prevalent abuse criterion. Six dependence criteria and all abuse criteria were reported reliably across cities (κ: 0.53–0.77). Seventeen of 19 withdrawal symptoms showed consistency in the reliability across cities. The most commonly reported reason for discrepant responses was ‘interpretation of question changed’. Only a small proportion of the total discrepancies were attributed to lying or social desirability. Conclusion The adopted DSM‐IV diagnostic classification for MDMA abuse and dependence was moderately reliable across cities. Findings on MDMA withdrawal support the argument that MDMA should be separated from other hallucinogens in DSM.     

Pill content, dose and resulting plasma concentrations of 3,4-methylendioxymethamphetamine (MDMA) in recreational 'ecstasy' users

Aims To improve our understanding of the pharmacology of ‘ecstasy’ in recreational environments; in particular, to describe the composition of ecstasy pills, patterns of ecstasy use and the relationship between dose of 3,4‐methylendioxymethamphetamine (MDMA) and resulting plasma concentrations. Design, setting and participants A naturalistic observational study of 56 experienced ‘ecstasy’ users in recreational settings in Australia. Measurements Drug use patterns (number of pills consumed, other drugs consumed). drug content of pills and resultant plasma concentrations of MDMA and related drugs were assessed by gas chromatography/mass spectrometry (GC/MS). Findings Ecstasy pills generally contained MDMA, but this was often combined with other drugs such as 3,4‐methylendioxyethylamphetamine (MDEA) and methamphetamine. The dose of MDMA per pill ranged from 0 to 245 mg and users consumed from one‐half to five pills, with the total dose consumed ranging up to 280 mg. Plasma concentrations of MDMA increased with number of pills consumed and cumulative MDMA dose. Use of larger numbers of pills was associated with extended exposure to the drug. Conclusions MDMA is the major active drug in ecstasy pills, but there is a high degree of variation in doses. Use of multiple pills over the course of one session is common and results in a sustained increase in MDMA plasma concentrations over a number of hours. This is likely to lead to a much greater exposure of the brain to MDMA than would be predicted from controlled single‐dose pharmacokinetic studies.     

Severe Ketoacidosis Complicated by ‘Ecstasy’ Ingestion and Prolonged Exercise

Ecstasy (3,4-methylenedioxymethamphetamine or MDMA) is used with increasing frequency as a recreational drug. Accumulated evidence over recent years indicates a growing demand for the drug with a corresponding increase in number of reports of adverse effects from its use. There are reported metabolic disturbances due to MDMA use. These, in addition to the prolonged exercise involved in dancing at ‘raves’ where MDMA may be used, may exacerbate ketoacidosis. We report two cases of ketoacidosis complicated by MDMA ingestion.     

Honoring the Admiral: Boerhaave-van Wassenaer''s syndrome

SUMMARY. Dr. Herman Boerhaave (1668–1738) first described esophageal rupture and the subsequent mediastinal sepsis based upon his careful clinical and autopsy findings and hundreds of references have since been written about Boerhaave's syndrome. Several fine historical accounts of this brilliant scientist have been published over the years and he has received appropriate credit for his valuable contributions. But what about that unfortunate propositus that Dr. Boerhaave attended to, performed necropsy upon, and subsequently received acclaim with? Medical history pays inadequate regard to the Baron Jan Gerrit van Wassenaer heer van Rosenberg, Prefect of Rhineland and Grand Admiral of the Dutch Fleet. This figure was a nobleman and war hero at the peak of the Dutch Golden Age who played his role in steering the course of European history. Without this nobleman's heroic contemporaneous account, Boerhaave's celebrated impact on medical science would never have been realized. Therefore, we offer an overdue recitation of Admiral van Wassenaer's biography. Based on found precedent we propose that spontaneous rupture of the esophagus be henceforth referred to as the ‘Boerhaave‐van Wassenaer's syndrome’.     

Death of the first white resident of North Queensland

The first white resident of North Queensland’s death certificate gives the final illness as ‘arthritis’. This examination of contemporary records and more recent reports, together with the results of discussion with colleagues interested in medicine and history, attempts to suggest the reasons for his various symptoms and his final demise. This life story is reminiscent of a ‘Boy’s own’ adventure with shipwrecks, survival at sea, coexistence with Aboriginal tribesmen before returning to ‘white society’, marriage and the start of a family. Are there lessons here for the twenty‐first century physician and rheumatologist? Would the commonplace illnesses of mid nineteenth‐century Queensland be very different to the problems seen in our outpatient clinics today?     

Severe congenital factor XIII deficiency caused by novel W187X and G273V mutations in the F13A gene; diagnosis and classification according to the ISTH/SSC guidelines

Factor XIII (FXIII) consists of the A and B subunits (FXIII‐A and FXIII‐B) and stabilizes fibrin clots. Defects in either the FXIII‐A or FXIII‐B gene lead to congenital FXIII deficiency, which manifests a life‐long haemorrhagic tendency. Thus, prophylactic FXIII replacement therapy is recommended. To establish a management plan for a 30‐year‐old male patient with ‘indefinite’ FXIII deficiency (<40% of the normal FXIII), he was characterized by state‐of‐the‐art techniques as guided by the FXIII/Fibrinogen subcommittee of ISTH/SSC. FXIII activity turned out to be virtually undetectable by three functional assays. Four immunological assays detected essentially no FXIII protein, FXIII‐A antigen, and A₂B₂ antigen, but normal FXIII‐B antigen. Accordingly, he was diagnosed as a ‘severe’ FXIII‐A deficiency case. He had no anti‐FXIII antibodies, because a 1:1 cross‐mixing test (ammonia release assay) and a five‐step mixing test (amine incorporation assay) between his plasma and normal plasma demonstrated deficiency patterns. Furthermore, a dosing test using plasma‐derived FXIII concentrates revealed its normal recovery. DNA sequencing analysis identified two novel mutations, W187X & G273V , in the F13A gene. Genetic analyses confirmed that he was a compound heterozygote and his mother and sister were heterozygotes of either one of these mutations, indicating the hereditary nature of this disorder. Molecular modelling predicted that the G273V mutation would cause clashes with the surrounding residues in the core domain of FXIII‐A, and ultimately would result in the instability of the mutant molecule. Detailed characterization of ‘indefinite’ FXIII deficiency made it possible to make its definite diagnosis and best management plan.     

Hyperkalemia in fatal MDMA ('ecstasy') toxicity

3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') is an amphetamine synthetic analog widely used as an recreational drug. Acute and severe toxic effects following MDMA ingestion include hyperthermia, arrhythmias, rhabdomyolisis, disseminated intravascular coagulation, hepatotoxicity and even death. Recently, we treated a patient in whom hyperkalemia, in the absence of renal failure, aggravated the expected toxic complications of MDMA, becoming the immediate cause of his death.     

Recreational MDMA use in Sydney: a profile of 'Ecstasy' users and their experiences with the drug

‘Ecstasy’ (3,4-methylenedioxymethampketamine or MDMA) is a recreational drug that is gaining popularity world wide. There is a paucity of research regarding the ways in which Ecstasy is used and the nature of its effects. A ‘snowball’ peer network technique was used to recruit 100 users who completed anonymous questionnaires. The research revealed that Ecstasy is primarily used by infrequent recreational drug users for ‘fun’ at dance parties and social gatherings. The primary reported effects of Ecstasy were a ‘positive mood state’ and feelings of intimacy and closeness to others. The secondary effects of Ecstasy were the stimulant effects of energy and activation, and the psychedelic effects of insight and perceptual and sensual enhancement. Ecstasy was reported to share the properties of both amphetamines and hallucinogens in the nature of its side effects and residual effects which were no more severe than those of the latter two classes of drug. It appeared Ecstasy was not conducive to regular and frequent use, because tolerance was reported to develop to the positive effects of Ecstasy, while negative effects increased with use. Although few problems associated with the recreational use of Ecstasy have surfaced to date, animal research has shown it to be neurotoxic to serotonergic nerve terminals. Caution must be observed until further research can determine the level of hazard in humans.     

Guideline on the prevention of secondary central nervous system lymphoma: British Committee for Standards in Haematology

The guideline group was selected to be representative of UK‐based medical experts. Ovid MEDLINE, EMBASE and NCBI Pubmed were searched systematically for publications in English from 1980 to 2012 using the MeSH subheading ‘lymphoma, CNS’, ‘lymphoma, central nervous system’, ‘lymphoma, high grade’, ‘lymphoma, Burkitt's’, ‘lymphoma, lymphoblastic’ and ‘lymphoma, diffuse large B cell’ as keywords, as well as all subheadings. The writing group produced the draft guideline, which was subsequently revised by consensus by members of the Haemato‐oncology Task Force of the British Committee for Standards in Haematology (BCSH). The guideline was then reviewed by a sounding board of ~50 UK haematologists, the BCSH and the British Society for Haematology (BSH) Committee and comments incorporated where appropriate. The ‘GRADE’ system was used to quote levels and grades of evidence, details of which can be found in Appendix I. The objective of this guideline is to provide healthcare professionals with clear guidance on the optimal prevention of secondary central nervous system (CNS) lymphoma. The guidance may not be appropriate to patients of all lymphoma sub‐types and in all cases individual patient circumstances may dictate an alternative approach. Acronyms are defined at time of first use.     

Eating psychopathology in young non‐clinical adults: a pilot study of the impact of parental personality

This pilot study aims to determine the effect of parental personality factors on their grown‐up children's eating attitudes. Thirty sets of non‐clinical participants (mother, father, young adult child) completed standardized measures of narcissism, borderline personality disorder characteristics and eating pathology. Data were analysed using correlations. There were specific associations between parental personality pathology and their child's eating attitudes in young adulthood, but only in relation to fathers' levels of maladaptive narcissism. The ‘martyred’ form of narcissism in fathers was linked to bulimic attitudes in their children, while their ‘controlling’ narcissism was linked with restrictive eating attitudes. These results add to the growing body of research demonstrating paternal influences on the development of eating attitudes. Potential clinical implications for family and individual therapy are also discussed. Copyright © 2005 John Wiley & Sons, Ltd and Eating Disorders Association.     

3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy"): pharmacology and toxicology in animals and humans

(±)3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”), a ring-substituted amphetamine derivative first synthesized in 1914, has emerged as a popular recreational drug of abuse over the last decade. Pharmacological studies indicate that MDMA produces a mixture of central stimulant and psychedelic effects, many of which appear to be mediated by brain monoamines, particularly serotonin and dopamine. In addition to its pharmacologic actions, MDMA has been found to possess toxic activity toward brain serotonin neurones. Serotonergic neurotoxicity after MDMA has been demonstrated in a variety of experimental animals (including non-human primates). In monkeys, the neurotoxic dose of MDMA closely approaches that used by humans. While the possibility that MDMA is also neurotoxic in humans is under investigation, other adverse effects of MDMA in humans have been documented, including various systemic complications and a number of untoward neuropsychiatric sequelae. Notably, many of the adverse neuropsychiatric consequences noted after MDMA involve behavioral domains putatively influenced by brain serotonin (e.g., mood, cognition and anxiety). Given the restricted status of MDMA use, retrospective clinical observations from suspecting clinicians will probably continue to be a primary source of information regarding MDMA's effects in humans. As such, this article is intended to familiarize the reader with the behavioral pharmacology and toxicology of MDMA, with the hope that improved recognition of MDMA-related syndromes will provide insight into the function of serotonin in the human brain, in health as well as disease.     

Psychostimulant use and the brain

Psychostimulant users are typically young adults. We have conducted a narrative review of neuropsychiatric harms associated with the psychostimulants methamphetamine/amphetamine, cocaine and 3,4‐methylenedioxymethamphetamine (MDMA), focusing on epidemiological factors, common clinical presentations, underlying causal mechanisms and treatment options. The major neuropsychiatric harms of psychostimulant use are stroke, neurocognitive impairment, Parkinson's disease, seizures and psychotic illness. These arise through a combination of acute monoamine release, longer‐term neurotransmitter effects and indirect effects. These effects are moderated by factors in the individual and in the pattern of substance use. Neuropsychiatric harms associated with psychostimulant use can thus lead to severe long‐term impairment.     

Der Hohepriester der Gicht – Sir Alfred Baring Garrod (1819–1907)

The name of Sir Alfred Baring Garrod is linked with the first detection of uric acid in blood and its accumulation in sufferers from gout as well as the formulation of the term rheumatoid arthritis. The disease concept formulated by him initially (especially in Germany) caused confusion and much discussion but has now become accepted worldwide. Garrod’s work on gout delivered important contributions to the elucidation of pathophysiological problems of the symptoms. Furthermore, he made a great contribution to the reorganization of the British Pharmacopoeia. One of his sons, the also knighted Sir Archibald Edward Garrod, initially continued the work of his father in the field of rheumatology and thereby made it really known. Later he developed his own research field with the establishment of the genetics of metabolism and introduced here the term inborn errors of metabolism.     

Cracking the neural code,treating paralysis and the future of bioelectronic medicine

The human nervous system is a vast network carrying not only sensory and movement information, but also information to and from our organs, intimately linking it to our overall health. Scientists and engineers have been working for decades to tap into this network and ‘crack the neural code’ by decoding neural signals and learning how to ‘speak’ the language of the nervous system. Progress has been made in developing neural decoding methods to decipher brain activity and bioelectronic technologies to treat rheumatoid arthritis, paralysis, epilepsy and for diagnosing brain‐related diseases such as Parkinson's and Alzheimer's disease. In a recent first‐in‐human study involving paralysis, a paralysed male study participant regained movement in his hand, years after his injury, through the use of a bioelectronic neural bypass. This work combined neural decoding and neurostimulation methods to translate and re‐route signals around damaged neural pathways within the central nervous system. By extending these methods to decipher neural messages in the peripheral nervous system, status information from our bodily functions and specific organs could be gained. This, one day, could allow real‐time diagnostics to be performed to give us a deeper insight into a patient's condition, or potentially even predict disease or allow early diagnosis. The future of bioelectronic medicine is extremely bright and is wide open as new diagnostic and treatment options are developed for patients around the world.     

Aplastic anaemia following exposure to 3,4-methylenedioxymethamphetamine ('Ecstasy')

Summary. We report two cases of aplastic anaemia following exposure to 'Ecstasy' (MDMA, 3,4-methylenedioxymethamphetamine). In both cases the aplastic anaemia resolved spontaneously 7–9 weeks after presentation. Long-term bone marrow culture study of one patient demonstrated complete normalization of haemopoiesis at time of haematological recovery, suggesting either that damage to the haemopoietic stem cell had been only transient, or that a more mature, committed progenitor cell was the target. Because MDMA may have been a factor in the aetiology of the bone marrow suppression in these two cases, we recommend close haematological monitoring of young adults presenting with toxicity from MDMA, and a detailed history of exposure to recreational drugs in all new patients presenting with aplastic anaemia.     

How we treat: considerations for physiotherapy in the patient with haemophilia and inhibitors undergoing elective orthopaedic surgery

Ten weeks prior to a scheduled left total knee arthroplasty, a 25‐year‐old man with severe haemophilia A and a high‐titre inhibitor presented to the physical therapist for a preoperative assessment at the haemophilia treatment centre (HTC). Prior to the recommendation to proceed to surgery, the therapist and other members of the multidisciplinary care team had surmised that, despite two previous radiosynovectomies, an arthroscopic synovectomy, and most recently at the age of 18 years, an arthroscopic debridement, the patient continued to have a progression of joint disease manifested by pain, restricted range of motion and reduced strength. Based on these findings and the patient’s history of consistent adherence to and follow‐through with recommended treatments, the HTC staff and orthopaedic surgeon determined that he was a good candidate for total knee replacement. The patient’s pain and joint disease severely limited his mobility and participation in functional activities. The most recent radiographs were notable for severe tricompartmental arthropathy of the left knee with joint deformity, flexion contracture, and osteoporosis. When queried about current haemostatic therapy during the initial preoperative visit with the physical therapist, the patient explained that he was self‐infusing a bypassing agent to treat active bleeds and as prophylactic treatment before participating in vigorous physical activity, as advised by his haematologist. He had previously managed his joint pain with cyclooxygenase‐2 inhibitors and both short‐ and long‐acting opioids, in addition to physical therapy. His current personal inventory of mobility and rehabilitative aids consisted of crutches, compressive wraps, and a cold‐compression unit. Further assessment of relevant environmental and psychosocial factors revealed that the patient was living with his girlfriend and 3‐year‐old daughter, for whom he was the primary caregiver, in a two‐story home with five steps to enter. He was also working part‐time from home as a computer consultant. The visit concluded with a formal physical assessment and discussion of next steps, including plans for additional preoperative physical therapy sessions. The therapist also informed the patient about what to expect postoperatively in terms of rehabilitation and recovery.     

Diffusion tensor imaging in MDMA users and controls: association with decision making

Diffusion Tensor Imaging (DTI) may provide information regarding effects of 3,4-methylenedioxymethamphetamine (MDMA) use on brain structure. Twelve MDMA users and 20 healthy controls underwent whole brain DTI data acquisition. Fractional anisotropy (FA), mean diffusivity (D(av)), and longitudinal (lambda(1)) and transverse (lambda(T)) diffusivities were compared between MDMA users and controls in 6 regions of the corpus callosum. MDMA users also completed the Barratt Impulsiveness Scale (BIS), and a subset of subjects completed the Iowa Gambling Task (IGT). Results showed significantly smaller lambda(1) in the rostral body of the corpus callosum in MDMA users, with no differences between groups on lambda(T), FA, or D(av). MDMA users also had a significantly higher BIS nonplanning score and greater preference for disadvantageous choices on the IGT. There was a significant positive correlation between lambda(1) in the rostral body of the corpus callosum and advantageous choices on the IGT. Further research on the etiology of these findings is warranted.