Chronic idiopathic axonal polyneuropathy and successful aging of the peripheral nervous system in elderly people

BACKGROUND: Chronic idiopathic axonal polyneuropathy (CIAP) is a frequent neurologic disorder in elderly persons. In view of the aging population, it is important to know the long-term prognosis of CIAP. OBJECTIVES: To determine if CIAP is influenced by the superposition of the effects of aging and to evaluate the severity of CIAP according to the disease duration. DESIGN: Controlled cohort study. SETTING: Outpatient clinic for neuromuscular diseases at the University Medical Center Utrecht, Utrecht, the Netherlands. PARTICIPANTS AND METHODS: One hundred twenty-seven patients with CIAP and 108 age-matched control subjects were included. We defined CIAP on the basis of symmetrical distal sensory or sensorimotor symptoms and signs with evolution over at least 6 months, exclusion of causes by history taking, results of clinical and laboratory investigations, and electrophysiologic findings that agreed with the diagnosis of axonal polyneuropathy. RESULTS: No important neurologic or electrophysiologic differences were found between patients with early-onset (before the age of 65 years) and late-onset (at or after the age of 65 years) CIAP, but patients with early-onset CIAP who had a short disease duration (<10 years) experienced more disability than patients with late-onset CIAP who had a similar disease duration. Old controls (age of 65 years or older) more often had symptoms, sensory signs in the legs, absent ankle jerks, and lower mean distal amplitudes of compound muscle action potentials and sensory nerve action potentials than young controls (aged <65 years). Absence of the sural nerve sensory nerve action potentials or presence of spontaneous muscle fiber activity in the anterior tibial muscle was common in patients with CIAP (51% and 60%, respectively), but exceptional (both 2%) in controls. CONCLUSIONS: Neither aging of the peripheral nervous system nor disease duration affects CIAP to a considerable degree, but CIAP has a greater influence on the daily life of nonretired patients with early-onset CIAP. The diagnosis of axonal polyneuropathy is probably supported best by either the absence of the sural nerve sensory nerve action potentials or the presence of spontaneous muscle fiber activity in the anterior tibial muscle.     

Automutilation after consumption of hallucinogenic mushrooms

Two young men, 25 and 32 years old, presented with severe automutilation by knife wounds after consumption of hallucinogenic mushrooms. The first patient had also used cocaine, cannabis and alcohol, while the second patient had only used the hallucinogenic mushrooms. Both patients were treated symptomatically and survived despite their severe stab wounds. Psilocybin-containing mushrooms are used as mind-altering drugs. These drugs may sometimes induce 'bad trips', a psychotic reaction accompanied by fear, panic, and dangerous behaviour, especially when used in combination with other drugs and alcohol or by psychiatrically unstable patients. During a bad trip, patients may hurt themselves. Because the duration of the psychotic and sympathicomimetic effects of psilocybin after ingestion of mushrooms is short (up to 6 h), and since psilocin itself causes no permanent organ toxicity, the treatment of psilocybin intoxication is only symptomatic. The diagnosis ofpsilocybin intoxication is hampered by the lack of routinely available, rapid and sensitive, analytical methods for the quantification ofpsilocybin and its active metabolite psilocin.     

Identification, expression and characterisation of a Babesia bovis hexose transporter

Babesia are tick-transmitted haemoprotozoan parasites that infect cattle, with an estimated 500 million at risk worldwide. Here, two predicted hexose transporters (BboHT1 and 2) have been identified within the Babesia bovis genome. BboHT1, having 40% and 47% amino acid sequence similarity compared with the human (GLUT1) and Plasmodium falciparum (PfHT) hexose transporters, respectively, is the only one that could be characterised functionally after expression in Xenopus laevis oocytes. Radiotracer studies on BboHT1 showed that it is a saturable, Na(+)-independent, stereo-specific hexose transporter, with a K(m) value for glucose of 0.84+/-0.54mM (mean+/-SEM). Using d-glucose analogues, hydroxyl positions at O-4 and O-6 have been identified as important for ligand binding to BboHT1. d-Glucose transport was inhibited maximally by cytochalasin B (50muM). A long-chain O-3 hexose derivative (compound 3361) that selectively inhibits PfHT also inhibited relatively potently BboHT1, with an apparent K(i) value of 4.1+/-0.9muM (mean+/-SEM). Compound 3361 did not inhibit B. bovis proliferation in in vitro growth assays but inhibited invasion of glucose-depleted bovine erythrocytes. Taken together with results of inhibition studies with cytochalasin B and beta-glucogallin, these data provide new insights into glucose metabolism of erythrocytic-stage Babesia infections.     

Pathophysiology of immune‐mediated demyelinating neuropathies—part I: Neuroscience

This first article of this review deals with neuroscientific aspects of immune‐mediated demyelinating neuropathies. It describes the anatomy and physiology of normal myelinated axons, methods of studying peripheral nerve physiology, pathophysiological consequences of demyelination or damage at the node of Ranvier, and the mechanisms that may lead to impaired axonal membrane dysfunction or axonal degeneration. This article (part I) will be followed by a second (part II) dealing with clinical aspects of these neuropathies. Muscle Nerve 48 : 851–864, 2013     

An economic evaluation of vial sharing of expensive drugs in automated compounding

International Journal of Clinical Pharmacy - Background Manual compounding of expensive cytotoxic drugs often leads to drug wastage, due to residual product in vials not being used. Aim To...     

In vitro cytokine production and proliferation of T cells from patients with anti‐proteinase 3‐ and antimyeloperoxidase‐associated vasculitis,in response to proteinase 3 and myeloperoxidase

Objective

To investigate in vitro proliferative responses of CD4+ T cells and generation of specific cytokines induced by stimulation of peripheral blood mononuclear cells (PBMCs) from patients with antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis with the autoantigens proteinase 3 (PR3) and myeloperoxidase (MPO).

Methods

PBMCs from vasculitis patients with PR3 ANCA or MPO ANCA and from healthy controls were stimulated for 7 days with PR3, MPO, or control stimuli. Proliferation of CD4+ T cells was assessed by flow cytometry, using the proliferation marker Ki‐67. Levels of the pro‐proliferative cytokines interleukin‐2 (IL‐2) and IL‐6 and of the Th1 and Th2 cytokines interferon‐γ (IFNγ) and IL‐10 in culture supernatants were determined.

Results

PR3 and MPO induced proliferative responses in CD4+ T cells from individual patients with ANCA‐associated vasculitides and healthy controls in vitro. Neither PR3 nor MPO elicited significant IL‐2 production. Levels of IL‐6 were highest after stimulation with PR3 but low after stimulation with MPO, independent of study group. Stimulation with PR3, and to a lesser extent with MPO, induced a Th2 cytokine milieu, characterized by high production of IL‐6 and IL‐10 and low production of IFNγ in patients and controls.

Conclusion

PR3 and MPO promote proliferation of CD4+ T cells from patients with ANCA‐associated vasculitides, but also cross‐stimulate T cells from healthy individuals. Strong IL‐10 production elicited by PR3 in vitro may act as an inhibitory signal for T cell proliferation and may have an important immunoregulatory function in vivo.