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BioRxiv : the Preprint Server For... Jan 2024As the primary Ca release channel in skeletal muscle sarcoplasmic reticulum (SR), mutations in the type 1 ryanodine receptor (RyR1) or its binding partners underlie a...
As the primary Ca release channel in skeletal muscle sarcoplasmic reticulum (SR), mutations in the type 1 ryanodine receptor (RyR1) or its binding partners underlie a constellation of muscle disorders, including malignant hyperthermia (MH). In patients with MH mutations, exposure to triggering drugs such as the halogenated volatile anesthetics biases RyR1 to an open state, resulting in uncontrolled Ca release, sarcomere tension and heat production. Restoration of Ca into the SR also consumes ATP, generating a further untenable metabolic load. When anesthetizing patients with known MH mutations, the non-triggering intravenous general anesthetic propofol is commonly substituted for triggering anesthetics. Evidence of direct binding of anesthetic agents to RyR1 or its binding partners is scant, and the atomic-level interactions of propofol with RyR1 are entirely unknown. Here, we show that propofol decreases RyR1 opening in heavy SR vesicles and planar lipid bilayers, and that it inhibits activator-induced Ca release from SR in human skeletal muscle. In addition to confirming direct binding, photoaffinity labeling using azipropofol (AziP ) revealed several putative propofol binding sites on RyR1. Prediction of binding affinity by molecular dynamics simulation suggests that propofol binds at least one of these sites at clinical concentrations. These findings invite the hypothesis that in addition to propofol not triggering MH, it may also be protective against MH by inhibiting induced Ca flux through RyR1.
PubMed: 38260485
DOI: 10.1101/2024.01.10.575040 -
African Journal of Paediatric Surgery :... Jan 2024Transanal endorectal pull-through (TERPT) has become one of the preferred treatments for Hirschsprung's disease (HD) in our setting. This report aims to evaluate the...
BACKGROUND
Transanal endorectal pull-through (TERPT) has become one of the preferred treatments for Hirschsprung's disease (HD) in our setting. This report aims to evaluate the current outcome of TERPT in the setting.
MATERIALS AND METHODS
A retrospective review of 71 children who had TERPT for histologically-confirmed HD in 11 years (2006-2017) in Nigeria.
RESULTS
There were 48 boys and 23 girls; aged 3 days-12 years at initial presentation (median = 10 months). Three (4.2%) patients had associated anomalies (duodenal atresia; anorectal malformation and sensorineural deafness with hypopigmented skin patches each). Age at TERPT was 2 months to 15 years (median = 3 years), with surgery waiting time of 1 month-14.9 years (median = 18 months). Sixty-six (93.0%) patients had rectosigmoid, four (5.6%) patients had long segment and one (1.4%) had total colonic disease. Five (7.0%) patients with large megacolon and one (1.4%) with the total colonic disease had assisted abdominal resection of the colon at TERPT. Seventeen (23.9%) patients had post-operative complications, including post-operative enterocolitis 8 (11.3%); anastomotic dehiscence 3 (4.2%); retained aganglionic segment 2 (2.8%); anastomotic stenosis 2 (2.8%), resulting in prolonged hospital stay (P = 0.0001; range = 1-30 days; median = 5 days). The mortality rate was 4.2% (3) from malignant hyperthermia in one patient and in 2 patients, the cause of mortality was unclear. Patients were followed up for 3-6 years (median = 3.5 years). Bowel movement stabilised to 2-4 times daily by 6 weeks after surgery.
CONCLUSION
TERPT is a safe treatment for HD in this setting with good short-term outcomes. Longer follow-up is necessary to further evaluate the long-term bowel movement outcomes.!
Topics: Male; Child; Female; Humans; Hirschsprung Disease; Colonic Diseases; Anastomosis, Surgical; Anorectal Malformations
PubMed: 38259012
DOI: 10.4103/ajps.ajps_93_22 -
Qatar Medical Journal 2023Parkinsonism-hyperpyrexia syndrome (PHS) is a potentially life-threatening condition that occurs due to the abrupt withdrawal or significant dose reduction of...
BACKGROUND
Parkinsonism-hyperpyrexia syndrome (PHS) is a potentially life-threatening condition that occurs due to the abrupt withdrawal or significant dose reduction of antiparkinsonian medications. It presents similarly to neuroleptic malignant syndrome (NMS) and is characterized by severe rigidity, fever, autonomic instability, and altered mental status.
CASE
A 62-year-old male with a 10-year history of Parkinson's disease (PD) underwent laparoscopic mesh repair for a left-sided diaphragmatic and large hiatus hernia. His antiparkinsonian medications included levodopa/carbidopa, amantadine, pramipexole, and benzhexol. Medications were withheld as part of the nil per os (NPO) status. Postoperatively, he developed withdrawal features, including tremors, difficulty speaking, tachycardia, hypertension, fever, and sweating. PHS, resulting from the withdrawal of antiparkinsonian medications, was diagnosed. The patient was transferred to the intensive care unit (ICU), intubated, and his antiparkinsonian medications were reintroduced. The patient's condition improved gradually, and he was discharged home on the 15th postoperative day.
DISCUSSION
The abrupt discontinuation of antiparkinsonian medications precipitated PHS in our patient. Recognizing the clinical picture of PHS and differentiating it from other possible conditions, such as neuroleptic malignant syndrome and malignant hyperthermia, is pivotal. Management involves resuming medications and providing supportive care. Early recognition and prompt reintroduction of the antiparkinsonian medications are essential for the patient's recovery.
CONCLUSION
PHS is a rare but potentially life-threatening condition that occurs due to the withdrawal of antiparkinsonian medications, leading to an acute hypodopaminergic state. Our case emphasizes the importance of careful perioperative management of antiparkinsonian medications and early recognition and management of withdrawal symptoms in patients with Parkinson's disease undergoing surgery.
PubMed: 38204562
DOI: 10.5339/qmj.2023.34 -
Cureus Jan 2024Intracranial immature teratomas are rare, highly malignant, and fast-growing with a poor prognosis. We report the case of an infant with a large immature teratoma in the...
Intracranial immature teratomas are rare, highly malignant, and fast-growing with a poor prognosis. We report the case of an infant with a large immature teratoma in the intracranial compartment. A two-month-old child presented to the emergency room with drowsiness and seizures. CT and cranial MRI showed hydrocephalus with a large expansive process in the right cerebral hemisphere extending to the infratentorial compartment, compressing the cerebellum and brainstem. It was then decided to partially resect the lesion. Postoperatively, due to the aggressiveness of the residual tumor, the patient developed complications (status epilepticus, hyperthermia, and electrolyte disorders) and died. Histopathological and immunohistochemical studies confirmed an immature teratoma. Teratomas are a subtype of germ cell tumors. Immature teratomas contain a population of cells that retain embryonic characteristics and tissues with more primitive components derived from all or some of the three germ layers (ectoderm, mesoderm, and endoderm). The prognosis of immature teratomas is associated with the degree of tumor differentiation, and those composed of undifferentiated embryonic tissues have a poor prognosis. This case report illustrates the rare and severe occurrence of a bulky immature cerebral teratoma in an infant. Unfortunately, despite undergoing a planned partial resection, the infant ended up having complications and died. Therefore, due to the size of the lesion in an infant, these cases are always complex when deciding on a surgical approach.
PubMed: 38196986
DOI: 10.7759/cureus.51891 -
International Journal of Hyperthermia :... 2024A meta-analysis was conducted to assess the efficacy and safety of cryoablation (CRA) compared with radiofrequency ablation (RFA). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
A meta-analysis was conducted to assess the efficacy and safety of cryoablation (CRA) compared with radiofrequency ablation (RFA).
METHODS
A systematic search of PubMed, EMBASE, Cochrane Library, Wanfang, CNKI, and VIP databases was conducted to identify clinical controlled studies comparing CRA versus RFA for hepatic malignancies up to July 2022. The meta-analysis was performed using RevMan 5.3.
RESULTS
A comprehensive analysis was conducted on 8 clinical controlled studies involving a total of 943 patients. There were no significant differences in the incidence of complications, complete ablation of lesions, local recurrence, and 1-year survival between the CRA and RFA groups (OR = 0.98, 95%CI: 0.61-1.55, = 0.92; OR = 1.08, 95%CI: 0.62-1.90, = 0.78; OR = 1.28, 95%CI: 0.49-3.36, = 0.61; and OR = 1.14, 95%CI: 0.63-2.06, = 0.66, respectively).
CONCLUSION
The efficacy and safety profile of CRA was comparable to that of RFA in the context of ablation therapy for hepatic malignancies. These findings suggested that CRA may be a valuable alternative to RFA in the treatment of hepatic malignancies.
Topics: Humans; Carcinoma, Hepatocellular; Cryosurgery; Liver Neoplasms; Radiofrequency Ablation
PubMed: 38190758
DOI: 10.1080/02656736.2023.2300347 -
World Journal of Emergency Medicine 2024
PubMed: 38188551
DOI: 10.5847/wjem.j.1920-8642.2024.006 -
Korean Journal of Anesthesiology Jun 2024The intraoperative use of tourniquets is associated with several complications, including hyperthermia. We present the first documented case of tourniquet-induced...
BACKGROUND
The intraoperative use of tourniquets is associated with several complications, including hyperthermia. We present the first documented case of tourniquet-induced hyperthermia in a pediatric patient at our institution.
CASE
A 5-year-old female with no past medical history underwent tendon release surgery for congenital talipes equinovarus under general anesthesia. Following inflation of a pneumatic tourniquet to a pressure of 250 mmHg on her left thigh, the patient experienced a gradual increase in body temperature. Despite the implementation of cooling measures, the temperature continued to increase until it plateaued. The hyperthermia gradually resolved upon deflation of the tourniquet.
CONCLUSIONS
Tourniquet-induced hyperthermia should be considered as a potential cause of intraoperative hyperthermia, particularly in the absence of typical signs of malignant hyperthermia. Early recognition and appropriate management, including deflation of the tourniquet and implementation of cooling measures, are crucial for preventing potential complications associated with hyperthermia.
Topics: Humans; Tourniquets; Female; Child, Preschool; Intraoperative Complications; Hyperthermia; Clubfoot; Anesthesia, General
PubMed: 38171593
DOI: 10.4097/kja.23655 -
Veterinarni Medicina Nov 2023Malignant hyperthermia (MH) is a clinical syndrome exhibiting elevation of expired carbon dioxide, hyperthermia, muscle rigidity, rhabdomyolysis, acidosis and...
Malignant hyperthermia (MH) is a clinical syndrome exhibiting elevation of expired carbon dioxide, hyperthermia, muscle rigidity, rhabdomyolysis, acidosis and hyperkalaemia, as well as cardiac dysrhythmia and renal failure. The syndrome manifests itself as a response to anaesthetic agents, such as e.g., halothane, desflurane, and succinylcholine. Depending on the animal species, MH is characterised by autosomal dominant or recessive inheritance, and so far two genes have been identified whose mutations can be linked to MH: and . In different species, various mutations of the gene have been described which may underlie MH. One of these mutations in dogs is T1640C, which results in the substitution of alanine for valine of the amino acid 547 (V547A) in the RYR1 protein. In our work, we aimed to investigate MH at the DNA level by identifying the T1640C mutation in a group of 50 dogs. For this purpose we used the PCR-RFLP technique, and in six dogs also direct sequencing of PCR products and subsequent comparison of their sequences with the RYR1 gene sequence in an online database. The results of our study show that none of the dogs analysed had any mutant allele of the RYR1 gene, indicating that none should be affected by MH.
PubMed: 38163044
DOI: 10.17221/46/2023-VETMED -
International Journal of Hyperthermia :... 2024Glioma constitutes the most common primary malignant tumor in the central nervous system. In recent years, microwave ablation (MWA) was expected to be applied in the...
Glioma constitutes the most common primary malignant tumor in the central nervous system. In recent years, microwave ablation (MWA) was expected to be applied in the minimally invasive treatment of brain tumors. This study aims to evaluate the feasibility and accuracy of microwave ablation in brain tissue by Shear Wave Elastography (SWE) to explore the application value of real-time SWE in monitoring the process of MWA of brain tissue. Thirty brain tissues were treated with different microwave power and ablation duration. The morphologic and microscopic changes of MWA tissues were observed, and the diameter of the ablation areas was measured. In this experiment, SWE is used to quantitatively evaluate brain tissue's degree of thermal injury immediately after ablation. This study It is found that the ablation range measured by SWE after ablation is in good consistency with the pathological range [ICCSWEL1-L1 = 0.975(95% CI:0.959 - 0.985), ICCSWEL2-L2 = 0.887(95% CI:0.779 - 0.938)]. At the same time, the SWE value after ablation is significantly higher than before (mean ± SD,9.88 ± 2.64 kPa 23.6 ± 13.75 kPa; < 0.001). In this study, the SWE value of tissues in different pathological states was further analyzed by the ROC curve (AUC = 0.86), and the threshold for distinguishing normal tissue from tissue after ablation was 13.7 kPa. The accuracy of evaluating ablation tissue using SWE can reach 84.72%, providing data support for real-time quantitative observation of the ablation range. In conclusion the accurate visualization and real-time evaluation of the organizational change range of the MWA process can be realized by real-time SWE.
Topics: Swine; Animals; Elasticity Imaging Techniques; Microwaves; Brain; Radiofrequency Ablation; Catheter Ablation
PubMed: 38159561
DOI: 10.1080/02656736.2023.2297649 -
Endokrynologia Polska 2023Radioactive iodine therapy (RIT) is an effective, safe, and cheap method in benign and malignant thyroid diseases. There is still an unresolved question of whether RIT...
Radioactive iodine therapy (RIT) is an effective, safe, and cheap method in benign and malignant thyroid diseases. There is still an unresolved question of whether RIT treatment also plays a role in the treatment of, for example, breast cancer, lung cancer, or glioblastoma multiforme (GBM). These studies are currently being carried out in rats in combination with genes, but it may be an interesting challenge to assess "pure" RIT alone, thanks to the expression of sodium iodide symporter (NIS), is effective in other organ nodules, both benign and malignant. Cloning of the NIS in 1996 provided an opportunity to use NIS as a powerful theranostic transgene. In addition, NIS is a sensitive reporter gene that can be monitored by high-resolution PET imaging using the radiolabels [¹²⁴I]sodium iodide ([¹²⁴I]NaI) or [18F] tetrafluoroborate ([¹⁸F]TFB). Based on published positron emission tomography (PET) results, [¹²⁴I]sodium iodide and internally synthesized [18F]TFB were compared in an orthotopic animal model of NIS-expressing glioblastoma. The results showed improved image quality using [¹⁸F]TFB. Based on these results, we will be able to extend the NIS gene therapy approach using non-viral gene delivery vehicles to target orthotopic tumour models with low-volume disease such as GBM. Is it possible to treat RIT alone without using the NIS gene in GBM? After all, the NIS symporter was detected not only in the thyroid gland, but also in different tumours. The administration of RIT is completely harmless; the only complication is hypothyroidism. Indeed, recently it has been shown that, for example, in the case of thyroid cancer, the maximum RIT is 37000 MBq (1000 mCi). When beneficial effects of therapy in GBM are not possible (e.g. neurosurgery, modulated electro-hyperthermia, chemotherapy, immunotherapy, cancer vaccines, or oncolytic viruses), could RIT provide a "revolution" using NIS?
Topics: Rats; Animals; Thyroid Neoplasms; Iodine Radioisotopes; Glioblastoma; Sodium Iodide; Lung Neoplasms; Antiviral Agents
PubMed: 38159203
DOI: 10.5603/ep.95505