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Pathophysiology
Published in Ibrahim Natalwala, Ammar Natalwala, E Glucksman, MCQs in Neurology and Neurosurgery for Medical Students, 2022
Ibrahim Natalwala, Ammar Natalwala, E Glucksman
A 41-year-old man with HD is prescribed haloperidol. The patient visits his GP weeks later complaining of increasing difficulty in ambulating. Vital signs include a temperature of 38.7°C, pulse rate of 124bpm, respiratory rate of 26 breaths per minute and blood pressure of 128/82 mmHg. Laboratory test results indicate a raised serum creatine kinase. What is the most appropriate pharmacological treatment for this patient’s presentation that has been caused by haloperidol? FlumazenilDantroleneNaloxoneAtropineAminocaproic acid
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Published in Henry J. Woodford, Essential Geriatrics, 2022
Blood tests may show an elevated creatine kinase (CK). EMG shows characteristic changes. Autoantibodies are more common in people with a younger onset (e.g. antinuclear antibody and anti-Jo-1 antibody). Muscle biopsy may help diagnosis. An underlying cause should be sought. Treatment is with immunosuppressant drugs.
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Published in Samar Razaq, Difficult Cases in Primary Care, 2021
McArdle’s syndrome is another glycogen storage disease, resulting in inefficient use of energy substrate in muscle due to muscle phosphorylase deficiency. Exercise results in cramp that tends to settle with a period of rest. Creatine kinase levels may be elevated. It is generally a benign disorder and may not even be picked up until later in adult life when the individual takes up strenuous exercise. No specific treatment exists but the patient should be advised to stop exercise on the onset of muscle cramps. Failure to do so may result in rhabdomyolysis, myoglobinuria and subsequent renal failure.
CARD9 deficiency promotes pancreatic cancer growth by blocking dendritic cell maturation via SLC6A8-mediated creatine transport
Published in OncoImmunology, 2023
Cheng Tian, Huimin Yuan, Yi Lu, Henghui He, Qing Li, Senlin Li, Jian Yang, Mengheng Wang, Ruochen Xu, Qian Liu, Ming Xiang
Creatine, an organic acid containing nitrogen, is associated with the progression and metastasis of PC20. It is also implicated in the activation of CD8+ T cells and polarization of macrophages21,22. Creatine is mainly synthesized by glycine amidinotransferase (GATM) and N-guanidinoacetate methyltransferase (GAMT) in the liver and kidney. GATM acts on glycine and L-arginine to produce guanidinoacetate, which is subsequently transformed into creatine by GAMT. Creatine is also transported into cells from circulation through solute carrier family 6 member 8 (SLC6A8), a specific transporter of creatine22, and is subsequently phosphorylated to phosphocreatine. Phosphocreatine is an energy storage metabolite that participates in ATP metabolism and provides energy for energy-consuming cells through the action of creatine kinase23. Cyclocreatine, a creatine analog, exerted the similar effect as creatine without the transporter SLC6A822. Cyclocreatine is phosphorylated to cyclocreatine phosphate, which provides energy for cells with high energy demands24.
Tolerability of long-term temperature controlled whole-body thermal treatment in advanced cancer-bearing dogs
Published in International Journal of Hyperthermia, 2022
B. Wylleman, L. Brancato, I. Gorbaslieva, E. van Zwol, M. G. M. C. Mori da Cunha, J. Benoit, D. Tierny, P. Vueghs, J. Van den Bossche, O. Rudenko, M. Janicot, J. Bogers
Overall, most blood parameters remained within their normal ranges during WBTT sessions. Slight decreases in urea and ionized calcium were noted in 4 dogs. Observed changes in other blood parameters reflect the impact on 4 organs or systems. First, there was a noticeable effect on the liver, as illustrated by an increase in the enzyme alanine aminotransferase (ALT, Figure 5). Simultaneously, there was a mild increase of alkaline phosphatase (ALP) in 6 out of 14 treatments and a stronger increase in the enzyme aspartate transaminase (AST) in all the 14 treatments. The latter can represent stress on skeletal muscles and the heart. This second observation is supported by the increase of creatine kinase (CK) levels in all 14 treatments. Third, there was an increase in cTnI. Last, there was also mild prolongation of blood clotting times. For prothrombin time (PT) this happened in 6 of the 14 sessions, whereas for activated partial thromboplastin time (aPTT) during 12 of the 14 sessions. In one case however, there was an important increase in aPTT, combined with spontaneous bleeding at the catheter site and from the nose. All changes in blood parameters were clinically non-significant and transient. They peaked at 24–48 h after WBTT and were found to be back within their normal ranges at the first follow-up visit at 14 days (no blood sampling after 48 h). It is very likely that the values normalized much faster, as it was observed in the first dog patient. This was the only animal that had a control visit 6 days after WBTT, finding that all parameters were already restored at that time (Figures 4 and 5).
Thr124Met myelin protein zero mutation mimicking motor neuron disease
Published in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2022
Giulia Bisogni, Angela Romano, Amelia Conte, Giorgio Tasca, Daniela Bernardo, Marco Luigetti, Andrea Di Paolantonio, Gian Maria Fabrizi, Agata Katia Patanella, Emiliana Meleo, Mario Sabatelli
Routine hematological examinations were within normal limits. The serum creatine kinase level was normal. Brain and spinal cord MRI were unremarkable. Analysis of TTR and HEXB genes and of major ALS-related genes, including SOD1, FUS, TARDBP, and C9ORF72, did not show any variant. Slowly progressive MND with subclinical sensory nerve involvement was diagnosed. Whole-body muscle magnetic resonance imaging (MRI) showed on T1-weighted images a pattern of reticular fatty replacement, consistent with neurogenic changes, in lower leg muscles, which were more evident in the distal part. The posterior compartment, with particular regard to the gastrocnemius medialis, was more involved than the anterior. Thigh muscles showed minimal changes while glutei were severely atrophic and fatty replaced (Figure 1).