CONTEXT: Methanol poisoning induces acute optic neuropathy with possible long-term visual damage. OBJECTIVE: To study the dynamics and key determinants of visual pathway functional changes during 4 years after acute methanol poisoning. METHODS: A total of 42 patients with confirmed methanol poisoning (mean age 45.7 ± 4.4 years) were examined 4.9 ± 0.6, 25.0 ± 0.6, and 49.9 ± 0.5 months after discharge. The following tests were performed: visual evoked potential (VEP), retinal nerve fiber layer (RNFL) measurement, brain magnetic resonance imaging (MRI), complete ocular examination, biochemical tests, and apolipoprotein E (ApoE) genotyping. RESULTS: Abnormal VEP P1 latency was registered in 18/42 right eyes (OD) and 21/42 left eyes (OS), abnormal N1P1 amplitude in 10/42 OD and OS. Mean P1 latency shortening during the follow-up was 15.0 ± 2.0 ms for 36/42 (86%) OD and 14.9 ± 2.4 ms for 35/42 (83%) OS, with maximum shortening up to 35.0 ms. No significant change of mean N1P1 amplitude was registered during follow-up. A further decrease in N1P1 amplitude ≥1.0 mcV in at least one eye was observed in 17 of 36 patients (47%) with measurable amplitude (mean decrease -1.11 ± 0.83 (OD)/-2.37 ± 0.66 (OS) mcV versus -0.06 ± 0.56 (OD)/-0.83 ± 0.64 (OS) mcV in the study population; both p < .001). ApoE4 allele carriers had lower global and temporal RNFL thickness and longer initial P1 latency compared to the non-carriers (all p < .05). The odds ratio for abnormal visual function was 8.92 (3.00-36.50; 95%CI) for ApoE4 allele carriers (p < .001). The presence of ApoE4 allele was further associated with brain necrotic lesions (r = 0.384; p = .013) and brain hemorrhages (r = 0.395; p = .011). CONCLUSIONS: Improvement of optic nerve conductivity occurred in more than 80% of patients, but evoked potential amplitude tended to decrease during the 4 years of observation. ApoE4 allele carriers demonstrated lower RNFL thickness, longer P1 latency, and more frequent methanol-induced brain damage compared to non-carriers.

• Klíčová slova
• Toxic optic neuropathy, apolipoprotein E, chronic axonal neurodegeneration, long-term visual sequelae, methanol poisoning, remyelination, visual evoked potential,
• MeSH
• apolipoprotein E4 genetika   MeSH
• časové faktory MeSH
• dospělí MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• methanol otrava   MeSH
• následné studie MeSH
• nemoci zrakového nervu chemicky indukované   diagnóza   genetika   patofyziologie   MeSH
• nervus opticus účinky léků   patofyziologie   MeSH
• poruchy zraku chemicky indukované   diagnóza   genetika   patofyziologie   MeSH
• prognóza MeSH
• prospektivní studie MeSH
• reakční čas MeSH
• rizikové faktory MeSH
• studie případů a kontrol MeSH
• zrak účinky léků   genetika   MeSH
• zrakové evokované potenciály MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• apolipoprotein E4 MeSH
• methanol MeSH

Methyl alcohol intoxication is a global problem with high mortality and long-term visual sequelae and severe brain damage in survivors. The role of neuroinflammation in the mechanisms of methyl alcohol-induced toxic brain damage has not been well studied. We measured the acute concentrations and dynamics of lipoxins LxA4 and LxB4 and the interleukins IL-4, IL-5, IL-9, IL-10, and IL-13 in the serum of patients treated with methyl alcohol poisoning and the follow-up concentrations in survivors two years after discharge from the hospital. A series of acute measurements was performed in 28 hospitalized patients (mean age 54.2 ± 5.2 years, mean observation time 88 ± 20 h) and the follow-up measurements were performed in 36 subjects who survived poisoning (including 12/28 survivors from the acute group). Visual evoked potentials (VEP) and magnetic resonance imaging of the brain (MRI) were performed to detect long-term visual and brain sequelae of intoxication. The acute concentrations of inflammatory mediators were higher than the follow-up concentrations: LxA4, 62.0 ± 6.0 vs. 30.0 ± 5.0 pg/mL; LxB4, 64.0 ± 7.0 vs. 34.0 ± 4.0 pg/mL; IL-4, 29.0 ± 4.0 vs. 15.0 ± 1.0 pg/mL; IL-5, 30.0 ± 4.0 vs. 13.0 ± 1.0 pg/mL; IL-9, 30.0 ± 4.0 vs. 13.0 ± 1.0 pg/mL; IL-10, 38.0 ± 5.0 vs. 16.0 ± 1.0 pg/mL; IL-13, 35.0 ± 4.0 vs. 14.0 ± 1.0 pg/mL (all p < 0.001). The patients with higher follow-up IL-5 concentration had prolonged latency P1 (r = 0.413; p = 0.033) and lower amplitude N1P1 (r = -0.498; p = 0.010) of VEP. The higher follow-up IL-10 concentration was associated with MRI signs of brain necrotic damage (r = 0.533; p = 0.001) and brain hemorrhage (r = 0.396; p = 0.020). Our findings suggest that neuroinflammation plays an important role in the mechanisms of toxic brain damage in acute methyl alcohol intoxication.

• Klíčová slova
• CNS damage, Interleukins, Lipoxins, Methyl alcohol poisoning, Neuroinflammation, Non-traumatic brain injury,
• MeSH
• biologické markery krev   MeSH
• časové faktory MeSH
• cytokiny krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mediátory zánětu krev   MeSH
• methanol otrava   MeSH
• mozek diagnostické zobrazování   účinky léků   patofyziologie   MeSH
• neurotoxické syndromy krev   diagnóza   mortalita   patofyziologie   MeSH
• prospektivní studie MeSH
• reakční čas účinky léků   MeSH
• zrakové evokované potenciály účinky léků   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• cytokiny MeSH
• mediátory zánětu MeSH
• methanol MeSH

• MeSH
• lidé MeSH
• methanol MeSH
• nemoci zrakového nervu * MeSH
• prospektivní studie MeSH
• zánět zrakového nervu * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• komentáře MeSH
• Názvy látek
• methanol MeSH

CONTEXT: The role of activation of lipid peroxidation in the mechanisms of acute methanol poisoning has not been studied. OBJECTIVE: We measured the concentrations of lipid peroxidation markers in acutely intoxicated patients with known serum concentrations of methanol and leukotrienes. METHODS: Blood serum samples were collected from 28 patients hospitalized with acute intoxication and from 36 survivors 2 years after discharge. In these samples, concentrations of 4-hydroxy-trans-2-hexenal (HHE), 4-hydroxynonenal (HNE), and malondialdehyde (MDA) were measured using the method of liquid chromatography-electrospray ionization-tandem mass spectrometry. RESULTS: The maximum acute serum concentrations of all three lipid oxidative damage markers were higher than the follow-up serum concentrations: HNE 71.7 ± 8.0 ng/mL versus 35.4 ± 2.3 ng/mL; p < .001; HHE 40.1 ± 6.7 ng/mL versus 17.7 ± 4.1 ng/mL; p < .001; MDA 80.0 ± 7.2 ng/mL versus 40.9 ± 1.9 ng/mL; p < .001. The survivors without methanol poisoning sequelae demonstrated higher acute serum concentrations of the markers than the patients with sequelae. A correlation between measured markers and serum leukotrienes was present: HNE correlated with LTC4 (r = 0.663), LTD4 (r = 0.608), LTE4 (r = 0.771), LTB4 (r = 0.717), HHE correlated with LTC4 (r = 0.713), LTD4 (r = 0.676), LTE4 (r = 0.819), LTB4 (r = 0.746), MDA correlated with LTC4 (r = 0.785), LTD4 (r = 0.735), LTE4 (r = 0.814), LTB4 (r = 0.674); all p < .001. Lipid peroxidation markers correlated with anion gap (r= -0.428, -0.388, -0.334; p = .026, .045, .080 for HNE, HHE, MDA, respectively). The follow-up serum concentrations of lipid oxidation markers measured in survivors with and without visual/neurological sequelae 2 years after discharge did not differ. CONCLUSION: Our results demonstrate that lipid peroxidation plays a significant role in the mechanisms of acute methanol poisoning. The acute concentrations of three measured biomarkers were elevated in comparison with the follow-up concentrations. Neuronal membrane lipid peroxidation seems to activate leukotriene-mediated inflammation as a part of the neuroprotective mechanisms. No cases of persistent elevation were registered among the survivors 2 years after discharge.

• Klíčová slova
• Methanol poisoning, lipid oxidative damage, lipid peroxidation, neuroinflammation,
• MeSH
• aldehydy krev   metabolismus   MeSH
• alkoholismus patofyziologie   MeSH
• biologické markery krev   MeSH
• inhibitory cysteinových proteinas krev   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metabolická aktivace fyziologie   MeSH
• methanol krev   otrava   MeSH
• následné studie MeSH
• peroxidace lipidů fyziologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 4-hydroxy-2-hexenal MeSH Prohlížeč
• 4-hydroxy-2-nonenal MeSH Prohlížeč
• aldehydy MeSH
• biologické markery MeSH
• inhibitory cysteinových proteinas MeSH
• methanol MeSH

PURPOSE: To study the dynamics and clinical determinants of chronic retinal nerve fiber layer thickness (RNFL) loss after methanol-induced optic neuropathy. DESIGN: Prospective cohort study. METHODS: All patients underwent complete ophthalmic evaluation including spectral-domain optical coherence tomography 3 times during 4 years of observation: 4.9 (±0.6), 25.0 (±0.6), and 49.9 (±0.5) months after discharge. PARTICIPANTS: Eighty-four eyes of 42 survivors of methanol poisoning, mean age (standard deviation) of 45.7 (±4.4) years; and 82 eyes of 41 controls, mean age 44.0 (±4.2) years. MAIN OUTCOME MEASURES: Global and temporal RNFL loss. RESULTS: Abnormal RNFL thickness was registered in 13 of 42 (31%) survivors of methanol poisoning and chronic axonal loss in 10 of 42 (24%) patients. Significant decrease of global/temporal RNFL thickness during the observation period was found in the study population compared to the controls (P < .001). The risk estimate of chronic global RNFL loss for arterial blood pH < 7.3 at admission was 11.65 (95% confidence interval 1.91-71.12) after adjusting for age and sex. The patients with chronic axonal degeneration demonstrated progressive visual loss in 7 of 10 cases. The patients with abnormal RNFL thickness had magnetic resonance signs of brain damage in 10 of 13 vs 8 of 29 cases with normal RNFL thickness (P = .003). Signs of brain hemorrhages were present in 7 of 13 patients with abnormal RNFL thickness vs 5 of 29 cases with normal RNFL thickness (P = .015). CONCLUSIONS: Methanol-induced optic neuropathy may lead to chronic retinal axonal loss during the following years. Arterial blood pH on admission is the strongest predictor of chronic RNFL thickness decrease. Chronic retinal neurodegeneration is associated with the progressive loss of visual functions and necrotic brain lesions.

• MeSH
• akutní nemoc MeSH
• axony účinky léků   patologie   MeSH
• časové faktory MeSH
• chronická nemoc MeSH
• discus nervi optici účinky léků   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• methanol otrava   MeSH
• mozek patologie   MeSH
• následné studie MeSH
• nemoci zrakového nervu chemicky indukované   diagnóza   patofyziologie   MeSH
• neurony sítnice účinky léků   patologie   MeSH
• optická koherentní tomografie metody   MeSH
• počítačová rentgenová tomografie MeSH
• progrese nemoci MeSH
• prospektivní studie MeSH
• retinální gangliové buňky účinky léků   patologie   MeSH
• rozpouštědla otrava   MeSH
• zraková ostrost MeSH
• zraková pole MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• methanol MeSH
• rozpouštědla MeSH

CONTEXT: The role of neuroinflammation in methanol-induced toxic brain damage has not been studied. OBJECTIVE: We studied acute concentrations and the dynamics of leukotrienes (LT) in serum in hospitalized patients with acute methanol poisoning and in survivors. METHODS: Series of acute cysteinyl-LT and LTB4 concentration measurements were performed in 28/101 hospitalized patients (mean observation time: 88 ± 20 h). In 36 survivors, control LT measurements were performed 2 years after discharge. RESULTS: The acute maximum (Cmax) LT concentrations were higher than concentrations in survivors: Cmax for LTC4 was 80.7 ± 5.6 versus 47.9 ± 4.5 pg/mL; for LTD4, 51.0 ± 6.6 versus 23.1 ± 2.1 pg/mL; for LTE4, 64.2 ± 6.0 versus 26.2 ± 3.9 pg/mL; for LTB4, 59.8 ± 6.2 versus 27.2 ± 1.4 pg/mL (all p < 0.001). The patients who survived had higher LT concentrations than those who died (all p < 0.01). Among survivors, patients with CNS sequelae had lower LTE4 and LTB4 than did those without sequelae (both p < 0.05). The LT concentrations increased at a rate of 0.4-0.5 pg/mL/h and peaked 4-5 days after admission. The patients with better outcomes had higher cys-LTs (all p < 0.01) and LTB4 (p < 0.05). More severely poisoned patients had lower acute LT concentrations than those with minor acidemia. The follow-up LT concentrations in survivors with and without CNS sequelae did not differ (all p > 0.05). The mean decrease in LT concentration was 30.9 ± 9.0 pg/mL for LTC4, 26.3 ± 8.6 pg/mL for LTD4, 37.3 ± 6.4 pg/mL for LTE4, and 32.0 ± 8.8 pg/mL for LTB4. CONCLUSIONS: Our findings suggest that leukotriene-mediated neuroinflammation may play an important role in the mechanisms of toxic brain damage in acute methanol poisoning in humans. Acute elevation of LT concentrations was moderate, transitory, and was not followed by chronic neuroinflammation in survivors.

• Klíčová slova
• Neuroinflammation, brain damage, leukotrienes, methanol poisoning, nontraumatic brain injury, sequelae of poisoning,
• MeSH
• akutní nemoc MeSH
• cystein krev   MeSH
• ethanol krev   MeSH
• formiáty krev   MeSH
• hospitalizace MeSH
• hydrogenuhličitany krev   MeSH
• koncentrace vodíkových iontů MeSH
• kreatinin krev   MeSH
• krevní glukóza metabolismus   MeSH
• laktáty krev   MeSH
• leukotrieny krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• methanol krev   otrava   MeSH
• mozek účinky léků   patologie   MeSH
• následné studie MeSH
• neurodegenerativní nemoci chemicky indukované   patologie   MeSH
• otrava krev   farmakoterapie   MeSH
• výsledek terapie MeSH
• zánět chemicky indukované   patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cystein MeSH
• cysteinyl-leukotriene MeSH Prohlížeč
• ethanol MeSH
• formiáty MeSH
• formic acid MeSH Prohlížeč
• hydrogenuhličitany MeSH
• kreatinin MeSH
• krevní glukóza MeSH
• laktáty MeSH
• leukotrieny MeSH
• methanol MeSH

BACKGROUND: Mutations in FOXL2 are known to cause autosomal dominant blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), variably associated with premature ovarian failure. In this study, we report results of mutational screening in a Czech and Slovak patient population with BPES. DESIGN: Case series. PARTICIPANTS: Thirteen probands of Czech and one proband of Slovak origin with BPES and their available family members. METHODS: Sanger sequencing and multiplex ligation-dependent probe amplification in 14 probands with BPES. Targeted mutational screening in first-degree relatives. MAIN OUTCOME MEASURES: Genetic characterization and phenotype evaluation in Czech and Slovak individuals with BPES and their family members. RESULTS: Eight different mutations were detected including three novel ones: c.5T>G; p.(Met2Arg), c.197C>A; p.(Ala66Glu) and c.701_702insTGCAGCCGCAGCGGCTGCAGCAGCTGCGGCTGCAGCCGC; p.(Ala222_Ala234dup). In one family, the molecular genetic cause of disease was not identified by the methodology used. In 13 pedigrees, a negative family history suggested a de novo origin, which could be confirmed by targeted mutational screening in four families. One 62-year-old female with the c.663_692dup30 mutation had an atypical phenotype presenting as moderate ptosis compensated by frontalis muscle contraction, no epicanthus inversus and no premature ovarian failure. CONCLUSIONS: The de novo mutation rate in FOXL2 is exceptionally high compared with other dominant disorders manifesting with an ocular phenotype. In cases reporting a negative family history, careful examination of both parents is important to exclude mild features of the BPES phenotype.

• Klíčová slova
• FOXL2, blepharophimosis-ptosis-epicanthus inversus syndrome, phenotype,
• MeSH
• blefarofimóza genetika   MeSH
• dítě MeSH
• DNA sondy MeSH
• dospělí MeSH
• fenotyp MeSH
• forkhead transkripční faktory genetika   MeSH
• genetické asociační studie MeSH
• kojenec MeSH
• kožní abnormality genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• missense mutace * MeSH
• mladiství MeSH
• multiplexová polymerázová řetězová reakce MeSH
• mutační analýza DNA MeSH
• předškolní dítě MeSH
• protein FOXL2 MeSH
• urogenitální abnormality genetika   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA sondy MeSH
• forkhead transkripční faktory MeSH
• FOXL2 protein, human MeSH Prohlížeč
• protein FOXL2 MeSH

CONTEXT: Visual disturbances due to the toxic effect of formic acid in acute methanol poisonings are generally transient. The subjective symptoms of visual toxicity may resolve within few weeks and fundoscopic signs of acute optic neuropathy subside within 1-2 months; therefore, the prevalence of long-term visual sequelae in the population of survivors of poisonings may be underestimated. OBJECTIVE: To study the prevalence and character of long-term visual sequelae of acute methanol poisonings based on the data from the Czech mass methanol outbreak in 2012. PATIENTS AND METHODS: A total of 50 patients with confirmed methanol poisoning were included in this longitudinal cross-sectional study, median age: 48 (range, 23-73) years. The following tests were performed: optical coherence tomography or OCT with evaluation of the retinal nerve fibers layer (RNFL), visual evoked potentials (VEP), magnetic resonance imaging (MRI) of brain, complete ocular examination (visual acuity/field, color vision, contrast sensitivity, and fundus), neurological examinations, and biochemical tests. RESULTS: Of 50 patients, 7/50 (14%) were discharged with diagnosed visual sequelae and 6/50 (12%) were discharged with both visual and central nervous system sequelae of poisoning. On the follow-up examination, 20/50 (40%) of the patients had long-term visual sequelae, with 8% of blindness. A total of 38% of the patients had abnormal (28% borderline) findings on RNFL, and 40% had abnormal (18% borderline) VEP. Among the patients discharged without detected visual sequelae, 8/37 (22%) had abnormal RNFL and VEP. Patients with visual sequelae had brain lesions more often (70% vs. 27%, p < 0.01). MRI identified optic nerve lesions in 2/20 cases with abnormal VEP only. The groups with and without visual sequelae differed in serum methanol, ethanol, HCO3-, formate, pH, anion gap, and base deficit (all p < 0.01). Visual disturbances on admission and coma were more prevalent in the patients with visual sequelae (p < 0.05). Patients with positive serum ethanol on admission were 93% less likely to have optical axonal damage (OR: 0.07 (95% CI: 0.01-0.8); p < 0.05). No association was found between visual sequelae and type of antidote administered, mode of hemodialysis, or folate substitution. Pre-hospital administration of ethanol seemed beneficial: these patients were 90% less likely to have abnormal RNFL findings (OR: 0.10 (95% CI: 0.02-0.52); p < 0.01). CONCLUSIONS: The long-term visual sequelae were clearly underestimated on discharge, suggesting a significantly higher amount of patients with long-term sequelae than earlier reported. Thorough examinations before discharge and during follow-up will likely uncover a higher morbidity also after methanol poisonings in general.

• Klíčová slova
• acute methanol poisoning, health sequelae of poisoning, hospital treatment, long-term visual damage, treatment outcome,
• MeSH
• akutní nemoc MeSH
• bazální ganglia účinky léků   patofyziologie   MeSH
• časové faktory MeSH
• diagnostické techniky oftalmologické MeSH
• dospělí MeSH
• epidemický výskyt choroby * MeSH
• hodnocení rizik MeSH
• lidé středního věku MeSH
• lidé MeSH
• lineární modely MeSH
• logistické modely MeSH
• longitudinální studie MeSH
• methanol otrava   MeSH
• mladý dospělý MeSH
• multivariační analýza MeSH
• nervus opticus účinky léků   patofyziologie   MeSH
• obnova funkce MeSH
• ochranné faktory MeSH
• odds ratio MeSH
• otrava diagnóza   epidemiologie   patofyziologie   terapie   MeSH
• poruchy zraku chemicky indukované   diagnóza   epidemiologie   patofyziologie   terapie   MeSH
• prediktivní hodnota testů MeSH
• prevalence MeSH
• průřezové studie MeSH
• retina účinky léků   patofyziologie   MeSH
• rizikové faktory MeSH
• rozdělení chí kvadrát MeSH
• senioři MeSH
• výsledek terapie MeSH
• zrak účinky léků   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• methanol MeSH

Hydroxocobalamin is an effective first-line antidote used mainly in monotherapy of cyanide poisonings, while the opinions are different on the effects of its combination with sodium thiosulfate. A 58-year-old male committed a suicide attempt by ingesting of 1200-1500 mg of potassium cyanide; he was unconscious for 1-1.5 min. after ingestion with the episode of generalized seizures. On admission to the ICU, the patient was acidotic (pH 7.28; HCO3 14.0 mmol/L, base excess -12.7 mmol/L, saturation O2 0.999) with high serum lactate (12.5 mmol/L). Hydroxocobalamin was administered 1.5 hr after ingestion in two subsequent intravenous infusions at a total dose of 7.5 g. The infusion was followed by continuous intravenous administration of 1 mL/hr/kg of 10% sodium thiosulfate at a total dose of 12 g. No complications and adverse reactions were registered. Serum lactate decreased to 0.6 mmol/L the same day, and arterial blood gases became normal (pH 7.49; HCO3 27.2 mmol/L, base excess 2.2 mmol/L, saturation O2 0.994). The follow-up examination 5 months later revealed no damage of basal ganglia and cerebellum on magnetic resonance imaging. The neurological examination revealed no pathological findings. On the ocular coherence tomography, the retinal nerve fibres layer was normal. In visual evoked potentials, there was a normal evoked complex on the left eye and minor decrease in amplitude on the right eye. Combination of hydroxocobalamin and sodium thiosulfate can have a positive effect on the survival without long-term neurological and visual sequelae in the cases of massive cyanide poisonings due to the possibility of a potentiation or synergism of hydroxocobalamin effects by sodium thiosulfate. This synergism can be explained by the different time-points of action of two antidotes: the initial and immediate effect of hydroxocobalamin, followed by the delayed, but more persistent effect of sodium thiosulfate.

• MeSH
• antidota aplikace a dávkování   terapeutické užití   MeSH
• hydroxokobalamin aplikace a dávkování   terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• kyanid draselný otrava   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pokus o sebevraždu MeSH
• thiosírany aplikace a dávkování   terapeutické užití   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antidota MeSH
• hydroxokobalamin MeSH
• kyanid draselný MeSH
• sodium thiosulfate MeSH Prohlížeč
• thiosírany MeSH

Genetic polymorphisms influence the metabolism of ethanol and methanol, but the potential effects of genetic predisposition on the clinical course, outcome and short-term health sequelae of acute methanol poisoning are unknown. To evaluate the role of the MEOS system in methanol poisoning, we analysed the effect of three polymorphisms (RsaI - rs2031920; PstI - rs3813867; insertion/deletion I/D) within the CYP2E1 enzyme (MEOS system) in 50 adult survivors of methanol poisoning and compared their genotype frequencies with 460 controls. The minor allele frequencies of all three polymorphisms were below 5% in both groups. We did not detect significant differences in the genotype frequencies between survivors of methanol poisoning and controls (p = 0.34 for the RsaI variant; p = 0.59 for the PstI variant and p = 0.21 for the I/D polymorphism). The carriers of at least one minor allele in the CYP2E1 gene had less severe clinical symptoms and better short-term outcome after acute poisoning. Variants within the CYP2E1 gene are likely not significant genetic determinants of acute methanol poisoning (if survivors are analysed), but they may influence the severity of methanol poisoning and its visual/central nervous system (CNS) outcome.

• MeSH
• alely MeSH
• cytochrom P-450 CYP2E1 genetika   MeSH
• dospělí MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• lidé středního věku MeSH
• lidé MeSH
• methanol otrava   MeSH
• mladý dospělý MeSH
• polymorfismus genetický * MeSH
• přežívající MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytochrom P-450 CYP2E1 MeSH
• methanol MeSH