Amphetamine-induced psychosis: Transition to schizophrenia and mortality in a small prospective sample.

BACKGROUND AND OBJECTIVES: We investigated transition from amphetamine-induced psychosis (AIP) to schizophrenia. METHODS: A sample of 28 individuals was identified while hospitalized for AIP. We reviewed their hospital records after six years. RESULTS: During follow-up, seven individuals (25%) died and nine (32%) had moved from the area. Of the remaining 12, four individuals (25%) were diagnosed with schizophrenia. These individuals were, at baseline, characterized by fewer hallucinatory symptoms and more homelessness. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Hospitalization for AIP was a relatively specific risk factor for schizophrenia and the mortality rate in AIP was high.

Influence of drugs of abuse and alcohol upon patients admitted to acute psychiatric wards: physician's assessment compared to blood drug concentrations.

In acute psychiatric services, rapid and accurate detection of psychoactive substance intake may be required for appropriate diagnosis and intervention. The aim of this study was to investigate the relationship between (a) drug influence as assessed by physicians and (b) blood drug concentrations among patients admitted to acute psychiatric wards. We also explored the possible effects of age, sex, and psychotic symptoms on physician's assessment of drug influence. In a cross-sectional study, the sample comprised 271 consecutive admissions from 2 acute psychiatric wards. At admission, the physician on call performed an overall judgment of drug influence. Psychotic symptoms were assessed with the positive subscale of the Positive and Negative Syndrome Scale. Blood samples were screened for a wide range of psychoactive substances, and quantitative results were used to calculate blood drug concentration scores. Patients were judged as being under the influence of drugs and/or alcohol in 28% of the 271 admissions. Psychoactive substances were detected in 56% of the blood samples. Altogether, 15 different substances were found; up to 8 substances were found in samples from 1 patient. Markedly elevated blood drug concentration scores were estimated for 15% of the patients. Physician's assessment was positively related to the blood drug concentration scores (r = 0.52; P < 0.001), to symptoms of excitement, and to the detection of alcohol, cannabis, and amphetamines. The study demonstrates the major impact of alcohol and drugs in acute psychiatric settings and illustrates the challenging nature of the initial clinical assessment.

Psychoactive substance use among patients admitted to an acute psychiatric ward: laboratory findings and associations with clinical characteristics.

BACKGROUND: Estimates of psychoactive substance use among acutely admitted psychiatric patients vary among studies, and few have used comprehensive laboratory methods. AIMS: This study used chromatography-based analyses of blood and urine to identify the rates of substance use among acute psychiatric admissions, and to study the associations with socio-demographic variables, clinical characteristics and patients' reports of symptoms, substance use and need for treatment. METHODS: A cross-sectional study was conducted in 2006/2007 in Oslo, Norway. Blood and urine samples were collected from 298 acute psychiatric admissions and extensively analysed for alcohol, medicinal and illicit drugs. Psychotic symptoms were assessed with the positive subscale of the Positive and Negative Syndrome Scale. Patient self-report questionnaires included the Alcohol and Drug Use Disorder Identification Tests. Patients were also asked if they needed professional help for substance use. RESULTS: Psychoactive substances were detected in 63% of the 298 admissions, medicinal drugs in 46%, alcohol in 12% and illicit drugs in 28%. Patients using alcohol had a high suicidal risk score at admission and the shortest length of stay (median 1 day). Use of illicit drugs was associated with psychotic symptoms and readmission. Self-report questionnaires indicated harmful use of alcohol for half of the patients and of other substances for one-third. A need for professional help for substance use was reported by one-third of patients. CONCLUSION: Given the high rates of substance use and the important clinical associations, drug screening seems warranted in acute psychiatric settings. Interventions designed for substance-using patients should be developed and integrated.

Recent substance intake among patients admitted to acute psychiatric wards: physician's assessment and on-site urine testing compared with comprehensive laboratory analyses.

This cross-sectional study of acute psychiatric admissions compared physicians' assessments of recent substance intake and on-site urine testing with comprehensive laboratory drug analyses. The sample comprised 325 consecutive admissions from 2 acute psychiatric wards. Physicians on call were asked to judge if the patient had recently taken benzodiazepines, opiates, alcohol, amphetamines, cannabis, or cocaine. Blood and urine samples were obtained and analyzed with chromatographic laboratory methods for a wide range of substances. A routine on-site urine screening test was performed in 92 of the cases. Physicians' assessments and on-site urine testing were compared with the reference standard of laboratory analyses. The sensitivity of the physician's assessment was highest for amphetamines (76%), followed by benzodiazepines (61%), opiates (57%), cannabis (55%), and cocaine (50%), whereas specificity was greater than 90% for all substances. The sensitivity of the on-site test ranged from 76% for amphetamine to 97% for cannabis, and specificity ranged from 82% for cannabis to 100% for cocaine. The study indicates clinical underdetection of recent substance intake among acute psychiatric admissions. On-site urine testing identified substance use that was not recognized by the physician's initial assessment, although specificity for cannabis and benzodiazepines was low. Chromatographic methods, which offered important supplementary information about substance use, should be considered for the routine screening of acutely admitted psychiatric patients.

Differentially Expressed Proteins in Intra Synovial Compared to Extra Synovial Flexor Tendon Grafts in a Rabbit Tendon Transplantation Model.

 Uncomplicated healing of grafts for tendon reconstruction remains an unsolved problem in hand surgery. Results are limited by adhesion formation and decreased strength properties, especially within the tight fibro-osseous sheath of the digits. This is especially problematic when an extra synovial tendon graft is used to replace an intra synovial flexor tendon. Compositional differences are likely to play an important role in these processes. The aim of this study was, therefore, to compare protein expression in pair-matched intra synovial tendon grafts with extra synovial tendon grafts, using a rabbit tendon injury model. We hypothesized that there would be significant differences in proteins critical for response to tensile loading and adhesion formation between the two groups. Using mass spectrometry and multivariate statistical data analysis, we found tissue-specific differences in 22 proteins, where 7 explained 93% (R2) of the variation, with a prediction of 81% (Q2). Among the highest discriminating proteins were Galectin, Histone H2A, and Periostin, which were found in a substantially larger amount in the extra synovial tendons compared to the intra synovial tendons. These findings may contribute to improved understanding of the differences in outcome seen after tendon reconstruction using tendon grafts with intra synovial and extra synovial grafts.

Drugs of abuse among acute psychiatric and medical admissions: laboratory based identification of prevalence and drug influence.

OBJECTIVE: To use laboratory based analyses of blood and urine to determine the prevalence and influence of drugs of abuse among acute psychiatric and medical admissions. METHOD: In a cross sectional study, urine and blood samples were collected from 100 psychiatric and 106 medical admissions and extensively analysed for legal drugs with abuse potential, alcohol and illegal drugs. Drug influence at the time of admission was estimated on the basis of blood drug concentrations. RESULTS: Legal drugs were found in 47% of the psychiatric and 42% of the medical admissions. Alcohol was detected in 8% of the psychiatric and 4% of medical admissions, and illegal drugs were detected in 36% of the psychiatric and 13% of the medical admissions. Drug influence was estimated in 26% of the psychiatric and 14% of the medical patients. CONCLUSION: This study shows widespread use of substances among psychiatric and medical inpatients and that many are under the influence of drugs on admission.

PXL01 in sodium hyaluronate results in increased PRG4 expression: a potential mechanism for anti-adhesion.

PURPOSE: To investigate the anti-adhesive mechanisms of PXL01 in sodium hyaluronate (HA) by using the rabbit lactoferrin peptide, rabPXL01 in HA, in a rabbit model of healing tendons and tendon sheaths. The mechanism of action for PXL01 in HA is interesting since a recent clinical study of the human lactoferrin peptide PXL01 in HA administered around repaired tendons in the hand showed improved digit mobility. MATERIALS AND METHODS: On days 1, 3, and 6 after tendon injury and surgical repair, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to assess mRNA expression levels for genes encoding the mucinous glycoprotein PRG4 (also called lubricin) and a subset of matrix proteins, cytokines, and growth factors involved in flexor tendon repair. RabPXL01 in HA was administered locally around the repaired tendons, and mRNA expression was compared with untreated repaired tendons and tendon sheaths. RESULTS: We observed, at all time points, increased expression of PRG4 mRNA in tendons treated with rabPXL01 in HA, but not in tendon sheaths. In addition, treatment with rabPXL01 in HA led to repression of the mRNA levels for the pro-inflammatory mediators interleukin (IL)-1ß, IL-6, and IL-8 in tendon sheaths. CONCLUSIONS: RabPXL01 in HA increased lubricin mRNA production while diminishing mRNA levels of inflammatory mediators, which in turn reduced the gliding resistance and inhibited the adhesion formation after flexor tendon repair.

A comparison of symptoms and drug use between patients with methamphetamine associated psychoses and patients diagnosed with schizophrenia in two acute psychiatric wards.

Psychosis induced by the use of amphetamine or methamphetamine leads to dramatic symptoms and frequent readmissions and poses diagnostic challenges. Earlier studies have often relied on history taking and/or urine samples to reveal drug use. The aim of this study was to compare the psychotic symptoms of two groups: (1) acutely admitted patients who tested positive for methamphetamines and were diagnosed with drug-induced or methamphetamine-induced psychoses and (2) acutely admitted patients who tested negative for methamphetamines and were diagnosed with schizophrenia. Blood and urine samples were used. In addition, we investigated whether the severity of symptoms, in those who tested positive, was related to the blood concentration of methamphetamine. Of 285 patients who volunteered blood and/or urine samples within 48h of admission, 37 (13%) had recently taken methamphetamine. Positive psychotic symptoms between the two groups were compared by PANSS using the positive subscale. The results showed no differences in positive psychotic symptoms between the two groups. The severity of positive psychotic symptoms in patients with three different levels of urine/blood methamphetamine concentrations, were compared. We found no clinically or statistically significant relationship between blood methamphetamine levels and severity of psychotic symptoms.

The major T cell epitope on type II collagen is glycosylated in normal cartilage but modified by arthritis in both rats and humans.

Type II collagen (CII) is a target for autoreactive T cells in both rheumatoid arthritis and the murine model collagen-induced arthritis. The determinant core of CII has been identified as CII260-270, and the alteration of this T cell epitope by posttranslational modifications is known to be critical for development of arthritis in mice. Using CII-specific T cell hybridomas we have now shown that the immunodominant T cell epitope in the normal (healthy) human and rat joint cartilage is O-glycosylated at the critical T cell receptor recognition position 264 with a mono- or di-saccharide attached to a hydroxylysine. In contrast, in the arthritic human and rat joint cartilage there are both glycosylated and non-glycosylated CII forms. Glycosylated CII from normal cartilage could not be recognized by T cells reactive to peptides having only lysine or hydroxylysine at position 264, showing that antigen-presenting cells could not degrade the O-linked carbohydrate. Thus, the variable forms of the glycosylated epitope are determined by the structures present in cartilage, and these vary during the disease course. We conclude that the chondrocyte determines the structures presented to the immune system and that these structures are different in normal versus arthritic states.

Role of the galactosyl moiety of collagen glycopeptides for T-cell stimulation in a model for rheumatoid arthritis.

Two protected derivatives of beta-D-galactopyranosyl-5-hydroxy-L-lysine, in which HO-4 of galactose has been O-methylated or replaced by fluorine, have been prepared. The building blocks were incorporated at position 264 of the peptide fragment CII259-273 from type II collagen by solid-phase synthesis. The ability of these two glycopeptides, and two CII259-273 glycopeptides in which HO-4 of galactose was either unmodified or deoxygenated, to elicit responses from T-cell hybridomas obtained in a mouse model for rheumatoid arthritis was then determined. The hybridomas were all highly sensitive towards modifications at C-4 of the beta-D-galactosyl residue of CII259-273, highlighting the role of HO-4 as an important contact point for the T-cell receptor. Most likely, this glycopeptide hydroxyl group is involved in hydrogen bonding with the T-cell receptor.

Glycopeptide specificity of helper T cells obtained in mouse models for rheumatoid arthritis.

Five protected analogues of beta-D-galactosyl-(5R)-5-hydroxy-L-lysine were prepared, in which the galactosyl moiety was modified by monodeoxygenation or inversion of stereochemistry at C-4. The building blocks were used in the solid-phase synthesis of a set of glycopeptides related to the peptide fragment CII256-273 from type II collagen. Evaluation of the glycopeptides revealed that T-cell hybridomas obtained in collagen-induced arthritis (CIA), which is a common mouse model for rheumatoid arthritis, recognized the galactosyl moiety with high specificity for individual hydroxy groups. Moreover, T-cell hybridomas obtained in a humanized variant of CIA were also found to recognize the glycopeptides in an equally carbohydrate-specific manner. The results allowed the generation of models of the complexes formed between the appropriate class II major histocompatibility complex (MHC) molecule, glycopeptide, and the T-cell receptor, that is, of an interaction that is critical for the stimulation of T cells in the arthritis models. In the structural models, peptide side chains anchor the glycopeptide in pockets in the class II MHC molecule, whereas the galactosylated hydroxylysine residue forms the key contacts with the T-cell receptor. Importantly, the results also suggest that a T-cell response towards glycopeptide fragments from type II collagen could play an important role in the development of rheumatoid arthritis in humans.

Predominant selection of T cells specific for the glycosylated collagen type II epitope (263-270) in humanized transgenic mice and in rheumatoid arthritis.

Rheumatoid arthritis (RA) is associated with certain MHC class II alleles and is characterized by a chronic autoimmune response in the joints. Using transgenic mice expressing human DR4 (DRB1*0401) and human CD4, but lacking endogenous MHC class II, we show that posttranslational glycosylation of type II collagen (CII) influences the level of T cell tolerance to this candidate cartilage-specific autoantigen. In such mice, the expression of human CII resulted in a tolerized murine T cell response to human CII. However, tolerance induction remained incomplete, preferentially deleting responses to the nonmodified CII 263-270 epitope, whereas T cell recognition of a glycosylated variant of this epitope was affected to a lesser degree. A similar dominance of T cell responses to CII-glycopeptides was recorded in a cohort of severely affected RA-patients (n = 14). Thus, RA T cells predominantly recognize the immunodominant CII peptide in its glycosylated form and may explain why previously it has been difficult to detect T cell responses to CII in RA patients.

Glycosylation of type II collagen is of major importance for T cell tolerance and pathology in collagen-induced arthritis.

Type II collagen (CII) is a candidate cartilage-specific autoantigen, which can become post-translationally modified by hydroxylation and glycosylation. T cell recognition of CII is essential for the development of murine collagen-induced arthritis (CIA) and also occurs in rheumatoid arthritis (RA). The common denominator of murine CIA and human RA is the presentation of an immunodominant CII-derived glycosylated peptide on murine Aq and human DR4 molecules, respectively. To investigate the importance of T cell recognition of glycosylated CII in CIA development after immunization with heterologous CII, we treated neonatal mice with different heterologous CII-peptides (non-modified, hydroxylated and galactosylated). Treatment with the galactosylated peptide (galactose at position 264) was superior in protecting mice from CIA. Protection was accompanied by a reduced antibody response to CII and by an impaired T cell response to the glycopeptide. To investigate the importance of glycopeptide recognition in an autologous CIA model, we treated MMC-transgenic mice, which express the heterologous CII epitope with a glutamic acid in position 266 in cartilage, with CII-peptides. Again, a strong vaccination potential of the glycopeptide was seen. Hence CII-glycopeptides may be the optimal choice of vaccination target in RA, since humans share the same epitope as the MMC mouse.