Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 4-month-old baby girl, after a period of apparent good health, began to have aphonia, dyspnea, difficulties with swallowing, cyanosis, apnea, and hypopnea during sleep that resulted in admission to an intensive care unit for intubation and mechanical ventilation. At the age of 9 months she was admitted to our hospital with a possible diagnosis of central hypoventilation syndrome. A polysomnographic study showed apnea and hypopnea (apnea + hypopnea index = 47.1), hypercapnia (mean end-tidal PCO2 89 +/- 15.0 mmHg), and arterial desaturation (mean SaO2 91 +/- 1.7%; lowest SaO2 < 50%; 68% of total sleep time at SaO2 below 93%); the study also showed an absent ventilatory response to CO2, absent cardiac responses to apnea during sleep, and right ventricular hypertrophy. Nocturnal nasal bi-level positive airway pressure (BIPAP), applied initially at 6 cmH2O and gradually increased to 16 cmH2O, caused the sleep-related abnormal respiratory events to disappear. End-tidal PCO2 decreased to 39 mmHg, and SaO2 increased to 94%. After 6 months of nocturnal BiPAP ventricular right hypertrophy reversed and arrested growth and hypotonia normalized. The child has tolerated and has remained on BiPAP support up to her current age of 3 years and continues to use this form of ventilatory assistance without difficulties.
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PMID:Bi-level positive airway pressure (BiPAP) ventilation in an infant with central hypoventilation syndrome. 926 57

The in vivo oxidation of fatty acids (FA) of different chain length was investigated in three patients with documented mitochondrial FA oxidation disorders: one patient with mild multiple acyl-CoA dehydrogenase deficiency (MADM), one with medium chain acyl-CoA dehydrogenase deficiency (MCAD), and one with carnitine palmitoyltransferase I deficiency (CPT I). Breath tests were performed after oral administration of 1-13C butyric. 1-13C octanoic, and 1-13C palmitic acids. 13C/12C ratio in the expired oxidative end product CO2 was measured. The cumulative 13C elimination was calculated and expressed as a percentage of the administered dose. In the MADM patient the influence of carnitine therapy (or deprivation) on the utilization of 1-13C palmitic acid was also examined. In the MCAD and CPT I patients, the 1-13C butyric, 1-13C octanoic and 1-13C palmitic acids in vivo oxidation were similar to five healthy controls. In the MADM patient, the oxidation of 1-13C butyric and 1-13C octanoic acids were normal, whereas the metabolism of 1-13C palmitic acid ranged from 33% of 66% of controls. In this patient the serum carnitine level decreased from 60 to 27 mumol/l without carnitine supplementation. Clinically there was mild hypotonia. 1-13C palmitic acid oxidation compared to controls was 50%. After 2 further weeks of carnitine deprivation the serum carnitine was 10-15 mumol/l. Clinically he was very hypotonic and had a large liver. 1-13C Palmitic acid oxidation was 33%. After 6 weeks of readministration of carnitine (L-carnitine 100 mg/kg/day p.o.) the serum carnitine was 60 mumol/l and the patient was in good clinical condition. 1-13C palmitic acid oxidation was 66% compared to controls. Our study implies that this simple fatty acid breath test is not of diagnostic use for detection of enzymatic defects in FA oxidation disorders. The carnitine dependent 1-13C palmitic acid oxidation indicates that this test might be of some value in cases with primary or secondary carnitine deficiencies.
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PMID:In vivo stable isotope studies in three patients affected with mitochondrial fatty acid oxidation disorders: limited diagnostic use of 1-13C fatty acid breath test using bolus technique. 926 22

Tetrahydrobiopterin (BH4) is synthesized from guanosine triphosphate (GTP) by GTP cyclohydrolase I (GCH), 6-pyruvoyltetrahydropterin synthase (PTS), and sepiapterin reductase (SPD). GCH is the rate-limiting enzyme. BH4 is a cofactor for three pteridine-requiring monooxygenases that hydroxylate aromatic L-amino acids, i.e., tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH), and phenylalanine hydroxylase (PAH), as well as for nitric oxide synthase (NOS). The intracellular concentrations of BH4, which are mainly determined by GCH activity, may regulate the activity of TH (an enzyme-synthesizing catecholamines from tyrosine), TPH (an enzyme-synthesizing serotonin and melatonin from tryptophan), PAH (an enzyme required for complete degradation of phenylalanine to tyrosine, finally to CO2 + H2O), and also the activity of NOS (an enzyme forming NO from arginine), Dominantly inherited hereditary progressive dystonia (HPD), also termed DOPA-responsive dystonia (DRD) or Segawa's disease, is a dopamine deficiency in the nigrostriatal dopamine neurons, and is caused by mutations of one allele of the GCH gene. GCH activity and BH4 concentrations in HPD/DRD are estimated to be 2-20% of the normal value. By contrast, recessively inherited GCH deficiency is caused by mutations of both alleles of the GCH gene, and the GCH activity and BH4 concentrations are undetectable. The phenotypes of recessive GCH deficiency are severe and complex, such as hyperphenylalaninemia, muscle hypotonia, epilepsy, and fever episode, and may be caused by deficiencies of various neurotransmitters, including dopamine, norepinephrine, serotonin, and NO. The biosynthesis of dopamine, norepinephrine, epinephrine, serotonin, melatonin, and probably NO by individual pteridine-requiring enzymes may be differentially regulated by the intracellular concentration of BH4, which is mainly determined by GCH activity. Dopamine biosynthesis in different groups of dopamine neurons may be differentially regulated by TH activity, depending on intracellular BH4 concentrations and GCH activity. The nigrostriatal dopamine neurons may be most susceptible to a partial decrease in BH4, causing dopamine deficiency in the striatum and the HPD/DRD phenotype.
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PMID:Regulation of pteridine-requiring enzymes by the cofactor tetrahydrobiopterin. 1032 73

The biological effects of low intensity ultrasound (US) in vitro; the mechanisms involved; and the factors that can enhance or inhibit these effects are reviewed. The lowest possible US intensities required to induce cell killing or to produce free radicals were determined. Following sonication in the region of these intensities, the effects of US in combination with either hyperthermia, hypotonia, echo-contrast agents (ECA), CO2, incubation time, high cell density or various agents were examined. The results showed that hyperthermia, hypotonia and microbubbles are good enhancers of the bioeffects, while CO2, incubation time and high cell density are good inhibitors. Cellular membrane damage is pivotal in the events leading to cell death, with the cellular damage-and-repair mechanism as an important determinant of the fate of the damaged cells. The optimal level of apoptosis (with minimal lysis) and optimal gene transfection efficiency were attained using a pulsed low intensity US. In summary, the findings suggest that low intensity US is potentially useful in therapy, while on the other hand, they also call for further investigation of such clinical scenarios as high-grade fever, edema or use of ECA which may lead to the lowering of the threshold for bioeffects with diagnostic US.
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PMID:Biological effects of low intensity ultrasound: the mechanism involved, and its implications on therapy and on biosafety of ultrasound. 1563 56

We report on a 19-year-old Russian man with Friedreich ataxia with an expanded GAA repeat. The symptoms include ataxia of the trunk and lower extremities, dysdiadochokinesia of the upper extremities with left side dominance, square wave jerks, dysarthria, decreased muscle tone, areflexia, hypesthesia, decreased vibration sense and weakness in the lower extremities, extensor plantar response, skeletal abnormalies, and hypertrophic cardiomyopathy. Somatosensory Evoked Potentials elicited by median nerve stimulation suggested involvement of the central pathways, including the posterior column with lateral dominance. Sural nerve biopsy showed a marked decrease in large myelinated fibers (120/mm2) and a moderate decrease in small myelinated fibers (1430/mm2) with normal density of unmyelinated fibers. Carbon dioxide laser stimulation of the upper limbs demonstrated "C-fiber component" toward Adelta fibers and a normal component toward C fibers. Immunohistochemical staining of a skin biopsy from the lateral malleolus for protein gene product 9.5 demonstrated a normal density (18/mm) of intraepidermal nerve fibers. To our knowledge, this is the first report using CO2 laser stimulation, skin biopsy, and sural nerve biopsy that unmyelinated fibers are not involved in Friedreich ataxia.
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PMID:[Neurological findings, neurophysiological examinations, and sural nerve biopsy in a case of Friedreich ataxia]. 1706 2

The study was aimed at the detection of endothelial factors contribution and nitric monoxide produced by constitutional and inducible NO-synthase in regulation of Ca-activated potassium channels activity of high conductivity in immobilization stress. The experiments were conducted in isolated rat-female hearts after retrograde perfusion with Krebs-Henseleit solution bubbled with 95% O2, 5% CO2 at 37 degrees C. To study BK(Ca)-channels role in the regulation of coronary vessels tone and contractile myocardial function BK(Ca)-channel blocker tetraethylammonium (ImM/l concentration) (Sigma, USA) was added in perfused solution. The obtained results justify: firstly, the non-selective blockade of constitutional and inducible NO-synthase L-NAME accompanied by the reduction of coronary flow volume velocity to control values level in the group of animals underwent to stress; second, selective blocker of inducible NO-synthase S-methylisotiourea completely eliminates evoked by stress hypotonia of cardiac vessels and reduction of contractile activity of left ventricle in stressed rats; thirdly, stress reduces the functional activity of Ca-activated potassium channels and the removal of endothelium or blockade of nitric monoxide completely it restores.
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PMID:[Nitrogen monoxide and functional activity of large conductance Ca-activated potassium channels in coronary vessels in rats with limited motor activity]. 1980 60

Joubert syndrome is a rare autosomal recessive disorder, which is characterized by absence or underdevelopment of the cerebellar vermis and severe developmental delay. The other common features include ataxia, an abnormal breathing pattern, abnormal eye movements and hypotonia. We report the anesthetic management in a 13-year-old girl with Joubert syndrome, scheduled for cauterization of nasal mucosa under general anesthesia. She had episodes of tachypnea and apnea. Oral midazolam 10 mg and famotidine 20 mg were administered 30 min before surgery. Anesthesia was induced and maintained with sevoflurane and nitrous oxide in oxygen. Vecuronium 2 mg was used to facilitate tracheal intubation. Mechanical ventilation was performed with a low ventilation setting of respiratory rate 5 beats x min(-1) and peak inspiratory pressure 9 cm H2O to maintain normal end-tidal CO2. Flurbiprofen axetil 30 mg was administered intravenously for analgesia, because opioids are not recommended. After reversal of muscle relaxation by atropin 0.5 mg and neostigmine 1.5 mg, her trachea was extubated. She did not develop postoperative apnea. In this patient with Joubert syndrome, midazolam, sevoflurane, nitrous oxide and flurbiprofen axetil were used without any complications.
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PMID:[General anesthesia for a girl with Joubert syndrome]. 2022 61

Carbon monoxide still remains one of the most common causes of fatal poisonings. Mechanisms of carbon monoxide toxic effects are complex and lead to hypoxia of body tissues. The most sensitive to tissue hypoxia are: the central nervous system and the cardiovascular system.The most characteristic cardiac symptoms of carbon monoxide poisoning are: stenocardial symptoms, hypotonia, myocardial dysfunction and arrhythmia (atrial fibrillation, tachycardia, bradycardia). Carbon monoxide connects with high affinity to metallo-proteins mainly to hemoglobin impairing oxygen transport in the body and to myoglobin, interfering with its function as oxygen reservoir among others in myocardium. Connecting to cytochrome oxidase in mitochondria it blocks the chain of electron transport which results in impairment of cellural respiration and formation of free radicals. Carbon monoxide has also relaxation effect against the smooth muscles of blood vessels, and thrombogenic effect. It is particularly adverse in patients with ischemic heart disease. In case of carbon monoxide poisoning one should always search for features of myocardial injury- as far as screening is concerned the most important ones are ECG and screening for cardiac troponin. Depending on the course of poisoning other laboratory (e.g. BNP) or imaging (echo-cardiography. scintiscanning, coronarography) tests may also prove to be useful.
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PMID:[Myocardial injury in the course of carbon monoxide poisoning]. 2324 21


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