Search Results (8)

Methaemoglobinaemia (MetHb) is a functional anaemia that can be life-threatening in severe cases. MetHb in adults and older children usually results from exposure to toxins from ingestion or skin exposure, whereas MetHb in infants under six months old usually occurs due to exposure to well water, severe metabolic acidosis from diarrhoea, or, in rare cases, secondary to cow’s milk protein allergy (CMPA). In this case report, a young infant presented acutely with shock secondary to profuse diarrhoea and MetHb requiring intravenous fluids and methylene blue and was subsequently diagnosed with CMPA. The early recognition and prompt treatment of CMPA may prevent the recurrence of MetHb symptoms and excessive diagnostic testing in this vulnerable population. Full article

Methylthioninium chloride (MTC) is a standard treatment for methaemoglobinaemia. A preparation of reduced MTC has been reported to increase blood oxygen saturation (SpO₂) and lower respiratory rates in patients with severe COVID-19. We have developed a stable form of reduced methylthionine (hydromethylthionine-mesylate, HMTM) having a benign safety profile in two Phase 3 trials in Alzheimer’s disease. The aim of this prospective study was to determine the effects of oral HMTM on SpO₂ and methaemoglobin (metHb) levels in a cohort of patients with mild hypoxaemia not due to COVID-19. Eighteen participants randomised to a single dose of 4, 75, 100 or 125 mg doses of HMTM had SpO₂ levels below 94% at baseline. Patients were routinely monitored by pulse oximetry after 4 h, and after 2 and 6 weeks of twice daily dosing. Significant ~3% increases in SpO₂ occurred within 4 h and were sustained over 2 and 6 weeks with no dose differences. There were small dose-dependent increases (0.060–0.162%) in metHb levels over 2 to 6 weeks. Minimum-energy computational chemistry revealed that HMT can bind within 2.10 Å of heme iron by donating a pair of electrons from the central nitrogen of HMT to d orbitals of heme iron, but with lower affinity than oxygen. In conclusion, HMTM can increase SpO₂ without reducing metHb by acting as a strong displaceable field ligand for heme iron. We hypothesise that this facilitates a transition from the low oxygen affinity T-state of heme to the higher affinity R-state. HMTM has potential as an adjunctive treatment for hypoxaemia. Full article

Para-aminopropiophenone (PAPP) is a methaemoglobin (MetHb) forming compound used for the lethal control of invasive carnivores and mustelids. By measuring the dose-dependent inhibition of O₂ transport arising from the oxidation of haemoglobin (HbFe²⁺) to MetHb (HbFe³⁺), we determined the sensitivity of nine bird species to PAPP. A methaemoglobinaemia absorbance index (MAI) was validated in five common bird species to determine thresholds associated with a 99% probability of survival (ST₉₉) and a 50% probability of mortality (LT₅₀). Dose–response trials in high conservation value birds sought MAI values below the ST₉₉ threshold, projecting the LT₅₀ value and avoiding the need for lethal outcomes. Black-backed gull (LT₅₀ = 1784.7) and eastern rosella (LT₅₀ = 1074 mg kg⁻¹) were the most tolerant species, while brown kiwi (LT₅₀ = 8.4 mg kg⁻¹) and weka (LT₅₀ = 9.3 mg kg⁻¹) were the most sensitive. Takahē were of intermediate acute sensitivity (LT₅₀ = 51 mg kg⁻¹), although protracted impacts on haemoglobin were observed in takahē up to 72 h later and associated with PAPP doses as low as 25.6 mg kg⁻¹. In pukeko (LT₅₀ = 138.4 mg kg⁻¹), protracted declines in haemoglobin 72 h later occurred at doses as low as 29.5 mg kg⁻¹, while at higher doses (253 and 112 mg kg⁻¹), deaths resulted after 4–6 days. Based upon PAPP doses that caused acute and protracted responses, we provide estimates for the lowest observable adverse effect level (LOAEL) and no observable effects level (NOEL) for nine bird species. Full article

A 70-year-old male patient was admitted to our dermatology outpatient clinic with newly developed personality changes and signs of hypoxemia. His anti-p200 Pemphigoid was treated with Dapsone for a few weeks. Due to generalized tonic-clonic seizure with a subsequent Glasgow Coma Scale of 5 points and a peripheral oxygen saturation not exceeding 88% under conditions of high-flow nasal cannula, he was intubated by the emergency team and transferred to the intensive care unit. Comprehensive tests were performed, but Dapsone-induced methemoglobinemia remained the exclusive explanation for the observed scenario, although arterial MetHb analysis showed a peak value of only 6%. The patient recovered shortly after repeated infusions of Methylene blue and Ascorbate, and cessation of Dapsone. We provide an overview of the pathophysiology, diagnostic procedures, and possible explanations for this case of Dapsone-induced methaemoglobinaemia. In conclusion, our case report provides evidence that even mild chronic methemglobinemia can induce severe clinical symptoms. Full article

Poppers are legal and largely used in France despite severe side effects, such as methaemoglobinaemia (MetHbia). Our work aimed to assess the prevalence of poppers consumers among patients with a MetHbia higher than or equal to 5% in French university hospitals and its evolution before and after the legalization of poppers in France. We conducted a national multicentre observational retrospective study. All patients for whom at least one MetHbia measurement was performed from 2012 to 2017 in university hospitals where the French addictovigilance network (FAN) is implanted were included. For each MetHbia measurement exceeding or equal to 5%, a return to the clinical file was made by the FAN to assess poppers consumption. We calculated the prevalence of MetHbia exceeding or equal to 5% and 25% and the prevalence of poppers consumption before and after the legalization. A total of 239 (0.14%) patients had a MetHbia level exceeding or equal to 5% with 25 (10.46%) cases of poppers consumption. Poppers consumption represented 68.4% (13 out of 19) of cases with MetHbia greater than or equal to 25%. Poppers consumption among patients with MetHbia exceeding or equal to 5% increased after the legalization from 4.76% to 11.67% (prevalence ratio PR = 2.45, 95% CI = [0.98–8.37], p-value = 0.190). The proportion of patients with a MetHbia level of 25% or more increased after the legalization from 4.76% to 8.63% (PR = 1.81, 95% CI = [0.68–6.82], p-value = 0.374). The use of poppers is very frequently reported by patients with MetHbia greater than or equal to 25%. Full article

Cytochrome b5 reductase 3 (CYB5R3) is a membrane-bound NADH-dependent redox enzyme anchored to the mitochondrial outer membrane, endoplasmic reticulum, and plasma membrane. Recessive hereditary methaemoglobinaemia (RHM) type II is caused by CYB5R3 deficiency and is an incurable disease characterized by severe encephalopathy with mental retardation, microcephaly, generalized dystonia, and movement disorders. Currently, the etiology of type II RHM is poorly understood and there is no treatment for encephalopathy associated with this disease. Defective CYB5R3 leads to defects in the elongation and desaturation of fatty acids and cholesterol biosynthesis, which are conventionally linked with neurological disorders of type II RHM. Nevertheless, this abnormal lipid metabolism cannot explain all manifestations observed in patients. Current molecular and cellular studies indicate that CYB5R3 deficiency has pleiotropic tissue effects. Its localization in lipid rafts of neurons indicates its role in interneuronal contacts and its presence in caveolae of the vascular endothelial membrane suggests a role in the modulation of nitric oxide diffusion. Its role in aerobic metabolism and oxidative stress in fibroblasts, neurons, and cardiomyocytes has been reported to be due to its ability to modulate the intracellular ratio of NAD⁺/NADH. Based on the new molecular and cellular functions discovered for CYB5R3 linked to the plasma membrane and mitochondria, the conventional conception that the cause of type II RHM is a lipid metabolism disorder should be revised. We hypothesized that neurological symptoms of the disease could be caused by disorders in the synapse, aerobic metabolism, and/or vascular homeostasis rather than in disturbances of lipid metabolism. Full article

Due to inaccessibility of potable water, rural communities drill boreholes within their homesteads despite vulnerability to groundwater contamination and associated health risks. This study assessed the quality of groundwater, identified potential sources of contamination and potential human health risks in Siloam Village, South Africa. Statistical difference between similar water quality parameters at different sites was determined at a significance level (α) of 0.05. Water quality parameters with serious potential health effects on human beings were correlated with selected water quality parameters to understand the nature of correlation and possible sources of contamination. Fluorides and nitrates had excessively high concentrations associated with tooth damage and pronounced skeletal fluorosis, and methaemoglobinaemia in infants and mucous membrane irritation in adults, respectively. There were statistically significant differences between means of most water quality parameters. Contrasting correlation of fluoride with calcium and pH indicated the need to further identify local sources and fluoride control mechanisms. Correlation of nitrate with chloride mostly indicated that faecal contamination is the potential source of high nitrates in groundwater. This requires further verification. Presence of total coliforms and E. coli in most boreholes indicated potential presence of faecal contamination. The need to educate borehole owners’ on possible strategies to minimise groundwater pollution was identified. Full article

Methaemoglobinaemia is a rarely diagnosed, life-threatening pathology and involves the presence of more than 1% of oxidised haemoglobin in the blood that is unable to carry oxygen. We report the case of a 49-year-old male who developed fulminant symptoms of acute hypoxaemic respiratory failure and in whom acute and chronic cardiovascular and respiratory conditions had been ruled out. The discrepancy between oxygen saturation determined by pulse oximetry and oxygen saturation and oxygen partial pressure determined by capillary blood gas analysis, as well as the evident lack of response to oxygen therapy, were important indicators suggestive of a haemoglobinopathy and the diagnosis of methaemoglobinaemia. His methaemoglobin level was 16%. The symptoms resolved spontaneously and the causative factor was not identified. Full article