A phase II study of continuous infusion recombinant human granulocyte- macrophage colony-stimulating factor as an adjunct to autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma in first remission

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) clearly hastens myeloid recovery in patients with relapsed hematologic malignancies undergoing autologous bone marrow transplantation (ABMT). In efforts to further improve neutrophil engraftment and shorten hospital stay in ABMT patients, rhGM-CSF was administered by a potentially more potent route (continuous infusion) to non-Hodgkin's lymphoma (NHL) patients with better BM reserve (first remission). Time to myeloid engraftment was compared with that of NHL patients treated in first remission at our institution on a similar ABMT protocol but without growth factor support (controls). Median neutrophil engraftment (absolute neutrophil count, 500 cells/microL) in first remission patients treated with rhGM-CSF was 14 days, compared with 22 days in controls (P = .0001). Hospital stays were also significantly reduced for rhGM-CSF patients (P = .0003). Platelet engraftment did not differ between the two groups. Persistent fever and generalized serositis were the primary toxicities. rhGM-CSF, delivered by this route, was efficacious but more toxic than 2-hour rhGM-CSF infusions previously reported by other investigators. Future alterations in both dose and schedule may retain comparable efficacy yet diminish toxicity.     

Analytical profile of N‐ethyl‐N‐cyclopropyl lysergamide (ECPLA), an isomer of lysergic acid 2,4‐dimethylazetidide (LSZ)

Recent investigations have shown that N‐ethyl‐N‐cyclopropyl lysergamide (ECPLA) produces LSD‐like behavioral effects in mice, which suggests that it may act as a hallucinogen in humans. Although the use of ECPLA as a recreational drug has been limited, key analytical data that can be used to detect ECPLA are required for future forensic and clinical investigations. ECPLA is an isomer of (2′S,4′S)‐lysergic acid 2,4‐dimethylazetidide (LSZ), a lysergamide that emerged as a recreational drug in 2013. Several analytical approaches were examined, including single‐ and tandem mass spectrometry platforms at low and high resolution, gas‐ and liquid chromatography (GC, LC), nuclear magnetic resonance spectroscopy (NMR), and GC condensed‐phase infrared spectroscopy (GC‐sIR). ECPLA and LSZ could be differentiated by NMR, GC‐sIR, GC, and LC‐based methods. The electron ionization mass spectra of ECPLA and LSZ contained ion clusters typically observed with related lysergamides such as m/z 150–155, m/z 177–182, m/z 191–197, m/z 205–208, and m/z 219–224. One of the significant differences in abundance related to these clusters included ions at m/z 196 and m/z 207/208. The base peaks were detected at m/z 221 in both cases followed by the retro‐Diels‐Alder fragment at m/z 292. Minor but noticeable differences between the two isomers could also be seen in the relative abundance of m/z 98 and m/z 41. Electrospray ionization mass spectra included lysergamide‐related ions at m/z 281, 251, 223, 208, 197, 180, and 140. LSZ (but not ECPLA) showed product ions at m/z 267 and m/z 98 under the conditions used.     

Return of the lysergamides. Part VI: Analytical and behavioural characterization of 1‐cyclopropanoyl‐d‐lysergic acid diethylamide (1CP‐LSD)

Lysergic acid diethylamide (LSD) is a prototypical serotonergic psychedelic drug and the subject of many clinical investigations. In recent years, a range of lysergamides has emerged with the production of some being inspired by the existing scientific literature. Others, for example various 1‐acyl substituted lysergamides, did not exist before their appearance as research chemicals. 1‐Cylopropanoyl‐LSD (1CP‐LSD) has recently emerged as a new addition to the group of lysergamide‐based designer drugs and is believed to be psychoactive in humans. In this investigation, 1CP‐LSD was subjected to detailed analytical characterizations including various mass spectrometry (MS) platforms, gas and liquid chromatography, nuclear magnetic resonance spectroscopy, solid phase and GC condensed phase infrared spectroscopy. Analysis by GC–MS also revealed the detection of artificially induced degradation products. Incubation of 1CP‐LSD with human serum led to the formation of LSD, indicating that it may act as a prodrug for LSD in vivo, similar to other 1‐acyl substituted lysergamides. The analysis of blotters and pellets is also included. 1CP‐LSD also induces the head‐twitch response (HTR) in C57BL/6 J mice, indicating that it produces an LSD‐like behavioural profile. 1CP‐LSD induced the HTR with an ED₅₀ = 430.0 nmol/kg which was comparable to 1P‐LSD (ED₅₀ = 349.6 nmol/kg) investigated previously. Clinical studies are required to determine the potency and profile of the effects produced by 1CP‐LSD in humans.     

Absconding from Public Mental Health Inpatient Units – Who Does it,and why?

Psychiatric Quarterly - Patients who abscond from acute inpatient psychiatric wards put themselves and others at risks of variable nature and severity. There is a limited understanding of what...     

Fragile X‐associated tremor/ataxia syndrome (FXTAS) in grey zone carriers

The grey zone (GZ; 45–54 CGG repeats in the FMR1 gene) is considered a normal allele; however, several studies have found a high frequency of GZ in movement disordered populations. Here, we describe neurological features of fragile X‐associated tremor/ataxia syndrome (FXTAS) in two carriers of GZ alleles, although FXTAS has been defined as occurring only in premutation carriers (55–200 CGG repeats). Both patients had family members who had premutation and were diagnosed with FXTAS. The presence of relatively high GZ alleles with elevated fragile X mental retardation 1 mRNA (FMR1‐mRNA) combined with a family history of FXTAS that may represent a facilitating genetic background for FXTAS are the factors that led to the presence of FXTAS in these individuals with a GZ allele. Further research into clinical involvement of GZ alleles is recommended and the definition of FXTAS may require revision.