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Nitrite, which has been mainly regarded as a chemical hazard, can induce infant methemoglobinemia. As for nitrite as a product of microbial metabolism, the contribution of the oral or gut microbiome has mostly received attention, whereas the role of nitrite-producing bacteria (NPBs) in food has been less elucidated. In this study, mesophilic NPBs were isolated from food samples (n = 320) composed of raw ingredients for weaning foods (n = 160; beetroot, broccoli, carrot, lettuce, rice powder, spinach, sweet potato, and honey) and processed baby foods (n = 160; cereal snack, cheese, yogurt, powdered infant formula, sorghum syrup, vegetable fruit juice, and weaning food). The phylogenetic diversity of the NPB strains was analyzed via 16S rRNA sequencing. All 15 food items harbored NPBs, with a prevalence of 71.9 % and 34.4 % for the raw ingredients and processed foods, respectively. The NPBs isolated from the foods were identified as Actinomycetota (Actinomycetes), Bacteroidota (Flavobacteriia, Sphingobacteriia), Bacillota (Bacilli), or Pseudomonadota (Alpha-, Beta-, and Gammaproteobacteria). Among the raw and processed foods, beetroot (85.0 %) and powdered infant formula (70.0 %) showed had the highest NPB prevalence (P > 0.05). Bacillota predominated in both types of food. The contamination source of Pseudomonadota, which was another major phylum present in the raw ingredients, was presumed to be the soil and endophytes in the seeds, whereas that of Bacillota was the manufacturing equipment used with the raw ingredients. Common species for probiotics, such as Lacticaseibacillus, Leuconostoc, Enterococcus, and Bacillus, were isolated and identified as NPBs. To our knowledge, this is the first study to reveal the taxonomical diversity and omnipresence of NPBs in food for babies. The results of this study highlight the importance of food-mediated microbiological risks of infant methemoglobinemia which are yet underrecognized., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The quality and quantity of groundwater resources are affected by landuse/landcover (LULC) dynamics, particularly the increasing urbanization coupled with high household wastewater discharge and decreasing open lands. This study evaluates temporal changes of groundwater quality for 2012 and 2019, its relation to Landuse/landcover, and its impact on Peshawar's residents (study area), Pakistan. A total of 105 and 112 groundwater samples were collected from tube wells in 2012 and 2019. Samples were then analyzed for seven standard water quality parameters (i.e., pH, electric conductivity (EC), turbidity, chloride, calcium, magnesium, and nitrate). Patient data for waterborne diseases were also collected for the years 2012 and 2019 to relate the impact of groundwater quality on human health. Landsat satellite images were classified for the years 2012 and 2019 to observe landuse/landcover dynamics concerning groundwater quality. Results manifested a decrease in groundwater quality for the year 2019 compared to 2012 and were more highlighted in highly populated areas. The nitrate concentration level was found high in the vicinity of agricultural areas due to the excessive use of nitrogenous fertilizers and pesticides, and thus the methemoglobinemia patients ratio increased by 14% (48-62% for the year 2012 and 2019, respectively). Besides, Urinary Tract Infections, Peptic Ulcer, and Dental Caries diseases increased due to the high calcium and magnesium concentration. The overall results indicate that anthropogenic activities were the main driver of Spatio-temporal variability in groundwater quality of the study area. The study could help district health administration understand groundwater quality trends, make appropriate site-specific policies, and formulate future health regulations., (© 2021. The Author(s).)

Background: Recognition of the agents most commonly implicated in causing methemoglobinemia can provide context for making therapeutic decisions and inform the diagnostic process. We evaluated the etiologic agents most commonly implicated in clinically significant methemoglobinemia using data from the National Poison Data System (NPDS)., Study Question: What are the most frequent etiologic agents associated with clinically significant methemoglobinemia., Study Design: This was a retrospective cross-sectional chart review using electronic data from the NPDS. The NPDS database was queried to identify cases from July 1, 2007, to June 30, 2017, that were coded as methylene blue treatment recommended and/or performed. Cases were excluded if the substance(s) have never been known to cause methemoglobin or the substances suggested methylene blue was used adjunctively for refractory shock (eg, calcium channel or beta blocker). Multiple substance exposures were reviewed and substances not known to cause methemoglobinemia were excluded., Measures and Outcomes: The primary end point was to summarize the most frequent etiologic agents associated with the administration of methylene blue for clinically significant methemoglobinemia., Results: There were 2563 substances reported in 1209 cases. After excluding coingestants and cases not associated with methemoglobinemia, there were 1236 substances. The top 4 substance categories were benzocaine, phenazopyridine, dapsone, and nitrates/nitrites., Conclusions: This study reveals the relative contribution of various drugs and chemicals associated with methylene blue administration. Over two-thirds of all cases were associated with benzocaine, phenazopyridine, dapsone, and nitrates/nitrites., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Methemoglobinemia (MetHb) is a rare congenital or acquired cause of infantile cyanosis. We examined the role of MetHb in a neonatal intensive care unit (NICU)., Study Design: A retrospective observational study was conducted reviewing blood gas analyses of hospitalized newborns over a 2-year period. MetHb-positive patients (MetHb >1.8%) were matched with a control group for gestational age, weight, disease, and illness severity at admission. Maternal, neonatal, clinical, and laboratory parameters were collected and analyzed in both groups., Results: MetHb incidence was 6%. The mean MetHb in the case group was 7.2%, and the first positive samples were observed at a mean of 22 days of life, 6 days prior to clinical or culture-proven sepsis. We identified low maternal age (31 vs. 34 years; p  = 0.038), sepsis (90 vs. 45%; p  = 0.022), and protracted parenteral nutrition (46 vs. 23 days; p  = 0.013) as risk factors for MetHb, and early minimal enteral feeding as protective factor (12th vs. 9th day; p  = 0.038)., Conclusion: MetHb has a high occurrence in NICU and can be a helpful prognostic indicator of an infectious process. Understanding and prompt identification of MetHb can allow pediatricians to implement a life-saving therapy., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Methemoglobin is formed when the iron center in hemoglobin is oxidized from ferrous iron to ferric iron. The functional consequence of this change is that hemoglobin is transformed to methemoglobin and cannot oxygenate tissues adequately, causing hypoxia and cyanosis. Infants have unique physiology that increases their risk of developing methemoglobinemia. Infants drink more water per body weight compared to children and adults, have lower NADH cyb5r reductase activity that converts methemoglobin to hemoglobin, and have a higher percentage of fetal hemoglobin, which is easier to convert to methemoglobin. A well-studied exposure to a chemical that can cause methemoglobinemia in infants is nitrate in well water. For the first part specifically about methemoglobin in infants, articles that were recent (2015-now) were given preference over articles that were older. Search terms included: methemoglobin, methemoglobinemia, infant, acquired, congenital, and methylene blue. For the latter half of the paper on nitrate and methemoglobinemia, preference was given to articles that described regionally important cases. In addition, search terms were: Minnesota, methemoglobinemia, nitrate, well water, drinking water, and infant. Acquired methemoglobinemia is rare, yet can still be seen in medical settings, and when an infant is exposed to nitrate in well water above 10 mg/L. To prevent exposure, parents should have their water tested for nitrate before the baby comes home. Physicians should make it practice to ask what the source of drinking water is for newly pregnant women and urge them to test for nitrate and bacteria if using a well. Using bottled water to make formula is also an option, but the best option is still breastfeeding., (Published by Elsevier Inc.)

A total of 1291 drinking water samples were examined for nitrite and nitrate during 6 months from December, 2015 to May, 2016 at 17 cities of Dakahlia governorate (Nile Delta, north of Egypt), and the results were utilized for assessment of health risk of the exposure from drinking water by calculating average daily intake (ADI), hazard quotient (HQ), and the hazard index (HI). The nitrite and nitrate in drinking water had a concentration range of 0.030-0.113 and 2.41-8.70 mg L -1 , with mean values of 0.059 ± 0.014 and 5.25 ± 1.61 mg L -1 , respectively. Nitrite and nitrate levels in rural areas and ground water samples were significantly higher than that in the urban ones. None of the analyzed samples exceeded WHO guideline values that set out to prevent methemoglobinemia. The values of HQ and HI for all age groups do not exceed unity indicating a low risk of methaemoglobinaemia for the population in this area. Results of the present study indicate that there is no health risk of residents from nitrite and nitrate through drinking water in the studied area. However, the other sources of exposure to nitrite and nitrate should be investigated in further studies.

Aim: Poppers have become legal in France since June 2013. Is their liberalisation associated with an increase of severe side effects observed?, Methods: To identify elevated methaemoglobinaemia related to poppers abuse, we reviewed all methaemoglobin concentrations measured in Nantes university hospital, during 12 months., Results: Methaemoglobin concentrations were superior to 25% in three cases of poppers consumption that occurred after the legalisation., Conclusion: Evaluating the prevalence of elevated methaemoglobinaemia could help to monitor severe complications of poppers use in France., (Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: Methemoglobinemia (MetHb) is a rare condition that may have mortal consequences. Literature shows cases of methemoglobinemia due to the use of lidocaine and other local anesthetics. This is a cross-sectional study to determine the incidence of methemoglobinemia after the application of lidocaine., Methods: In this study, 88 patients admitted to the emergency department of a university hospital between May 2014 and May 2015 and needed lidocaine application for small surgical procedures were included. When compared before and after the administration of lidocaine <2 mg/kg and >2 mg/kg, there was not a significant difference in the level of methemoglobin, hemoglobin, or in the hematocrit (p=0.604, p=0.502, and p=0.367, respectively)., Results: Mean age of the patients was 33.85 (±17.58) years, and 83% of the patients were male. Methemoglobin levels were not significantly different before and after the procedures (p>0.05)., Conclusion: The results of our study were consistent with the literature; lidocaine associated methemoglobinemia is a rare complication.

Type I congenital methemoglobinemia is an autosomal recessive disorder. A high frequency of congenital methemoglobinemia has been reported among Native Americans inhabiting the Yukon-Kuskokwim Delta. Other rare cases of congenital methemoglobinemia of types I and II have been reported in Japan and other countries. In Russia-namely, in Yakutia-a high frequency of type I congenital methemoglobinemia has been reported. In 2009, the Consultation Polyclinic of the Pediatric Center in Yakutsk city established a registry of children with congenital methemoglobinemia. In total, 43 patients were registered between 2005 and 2009. The median methemoglobin level was 13.5% (ranging between 4.2% and 33.9%) and physical examination revealed cyanosis of the skin and mucus membranes. There were significant positive relationships between percentage of methemoglobin and erythrocyte count, hemoglobin concentration, and hematocrit among male patients, consistent with an upregulation of the hypoxic response. The prevalence per 100,000 children ranged from 12.7 to 47.0 in 3 geographic regions of Yakutia. Further research is needed to clarify the clinical consequences of congenital methemoglobinemia in the children of Yakutia and the reasons for the high variability in the prevalence of the condition.

Objectives: To assess the impact of the Parklife annual music festival on the local hospital, North Manchester General., Methods: Data was obtained retrospectively by analysis of emergency department records during the weekend of Parklife 2015., Results: 32 patients were identified, 56% reported taking drugs. 34% were admitted for overnight observation. 4 patients presented with methaemoglobinaemia following oral ingestion of amyl nitrate. One patient had a methaemoglobin fraction of 90.6%, which is amongst the most extreme recorded in literature., Conclusion: Music festivals can impose a burden on local health services. Organisers should operate an efficient surveillance system in order to prevent the sale and use of recreational drugs, providing adequate on-site health services and working in collaboration with local emergency services.

We report the clinical features and molecular characterization of 23 patients with cyanosis due to NADH-cytochrome b5 reductase (NADH-CYB5R) deficiency from India. The patients with type I recessive congenital methemoglobinemia (RCM) presented with mild to severe cyanosis only whereas patients with type II RCM had cyanosis associated with severe neurological impairment. Thirteen mutations were identified which included 11 missense mutations causing single amino acid changes (p.Arg49Trp, p.Arg58Gln, p.Pro145Ser, p.Gly155Glu, p.Arg160Pro, p.Met177Ile, p.Met177Val, p.Ile178Thr, p.Ala179Thr, p.Thr238Met, and p.Val253Met), one stop codon mutation (p.Trp236X) and one splice-site mutation (p.Gly76Ser). Seven of these mutations (p.Arg50Trp, p.Gly155Glu, p.Arg160Pro, p.Met177Ile, p.Met177Val, p.Ile178Thr, and p.Thr238Met) were novel. Two mutations (p.Gly76Ser and p.Trp236X) were identified for the first time in the homozygous state globally causing type II RCM. We used the three-dimensional (3D) structure of human erythrocyte NADH-CYB5R to evaluate the protein structural context of the affected residues. Our data provides a rationale for the observed enzyme deficiency and contributes to a better understanding of the genotype-phenotype correlation in NADH-CYB5R deficiency., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: After an outbreak of Pneumocystis pneumonia (PCP) in our nephrology unit, dapsone was used as the second-line chemoprophylactic agent. Dapsone is the most common cause of drug-induced methemoglobinemia (MHb). Its prevalence is poorly described in the renal transplant population. Because dapsone is excreted by the kidneys, we hypothesized that the rate of MHb in these patients would be higher than previously reported. We aimed to describe the demographics, risk factors, and presenting features of MHb in these renal transplant patients., Methods: Twenty-six transplant recipients commenced on dapsone for chemoprophylaxis against PCP from February to September 2011. All patients had normal glucose-6-phosphate dehydrogenase levels before treatment. Characteristics of patients with MHb were compared with those of the rest of the cohort to determine potential risk factors., Results: Twelve (46%) patients developed MHb (levels 6.4 ± 4.1%). Six (50%) of the patients with MHb were asymptomatic on presentation. Cases had a mean drop in hemoglobin of 19 ± 7%. MHb led to five admissions (median length of stay 5 days, range 1-10 days). MHb level showed a strong correlation with the length of stay (correlation coefficient 0.762, P = 0.002)., Conclusion: This is the highest reported prevalence of MHb, to our knowledge, in patients receiving dapsone, and its use led to significant hospitalization in this population. This study raises concerns about the use of dapsone as chemoprophylaxis in renal transplant recipients., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Importance: Methemoglobinemia is a rare but serious disorder, defined as an increase in oxidized hemoglobin resulting in a reduction of oxygen-carrying capacity. Although methemoglobinemia is a known complication of topical anesthetic use, few data exist on the incidence of and risk factors for this potentially life-threatening disorder., Objective: To examine the incidence of and risk factors for procedure-related methemoglobinemia to identify patient populations at high risk for this complication., Design and Setting: Retrospective study in an academic research setting., Participants: Medical records for all patients diagnosed as having methemoglobinemia during a 10-year period were reviewed., Exposures: All cases of methemoglobinemia that occurred after the following procedures were included in the analysis: bronchoscopy, nasogastric tube placement, esophagogastroduodenoscopy, transesophageal echocardiography, and endoscopic retrograde cholangiopancreatography., Main Outcomes and Measures: Comorbidities, demographics, concurrent laboratory values, and specific topical anesthetic used were recorded for all cases. Each case was compared with matched inpatient and outpatient cases., Results: In total, 33 cases of methemoglobinemia were identified during the 10-year period among 94,694 total procedures. The mean (SD) methemoglobin concentration was 32.0% (12.4%). The methemoglobinemia prevalence rates were 0.160% for bronchoscopy, 0.005% for esophagogastroduodenoscopy, 0.250% for transesophageal echocardiogram, and 0.030% for endoscopic retrograde cholangiopancreatography. Hospitalization at the time of the procedure was a major risk factor for the development of methemoglobinemia (0.14 cases per 10,000 outpatient procedures vs 13.7 cases per 10,000 inpatient procedures, P < .001)., Conclusions and Relevance: The overall prevalence of methemoglobinemia is low at 0.035%; however, an increased risk was seen in hospitalized patients and with benzocaine-based anesthetics. Given the potential severity of methemoglobinemia, the risks and benefits of the use of topical anesthetics should be carefully considered in inpatient populations.

Methaemoglobinaemia is a rare condition of unknown prevalence. Diagnostic tests in resource limited settings are very rare but clinical signs can be a good guide. We set out to describe a case of Methaemoglobinaemia, raise awareness among practitioners in resource limited settings and to share experiences in its diagnosis and management. A previously well three and a half year old girl was admitted with central cyanosis of sudden onset. She underwent clinical, laboratory and radiological evaluation. Having been in a resource limited setting, the process of making a diagnosis was slow and difficult. After the diagnosis, the treatment was not available in the country but we managed to get it all the way from Nairobi, Kenya. A diagnosis of Methaemoglobinaemia was made using Spectrophotometry and she was successfully treated using 2 doses of intravenous Methylene blue. The cause of Methaemoglobinaemia was established to have been nitrites from food preservatives.

The retrospective cohort study described in this article examined 150 Iowa private well users' (aged 1-60 years) drinking water below the 10 parts per million nitrate-nitrogen (nitrate-N) maximum contaminant level and analyzed health history data and blood samples including hemoglobin fractions and immunological parameters. Positive associations existed (bivariate fit) between higher nitrate exposure and body mass index, lower recreational activity, perceived poorer health, and perceptions of susceptibility to illness. A directly proportionate relationship was seen between methemoglobin level in the blood and nitrate ingestion. High tumor necrosis factor-beta (TNF-beta) expression was also seen (bivariate fit, f = 3.76, p = .05). Complaints of stomach/ intestinal difficulties (heartburn/reflux > 50%; f = 5.274, p = .0231) and bone, muscle, and nerve complaints (osteoarthritis [rheumatoid excluded] = 47%; f = 6.0533, p = .0150) were found with increasing nitrate exposure. In vivo exposures of nitrate-N associated with complaints of bone/joint disorders or with altered ex vivo production of TNF-beta or Th2/Treg cytokine interleukin-10 have not been previously illustrated with environmental exposures.

Background: Occasionally, patients suffer systemic adverse effects from injections of local anaesthetic solutions. This may range from minor transient vasovagal attacks to life-threatening collapse., Methods: The suspected adverse reactions reported to the Office of Product Review of the Therapeutic Goods Administration (TGA) were analysed in detail., Results: There was a high incidence (70%) of adverse reactions associated with prilocaine, which is much greater than its market share (less than 20%). There is a tendency to consider all systemic adverse reactions as being 'allergic' reactions although this is rarely the case. Syncope, cardiovascular and central nervous system reactions are much more common. There is also a risk of methaemoglobinaemia to prilocaine and articaine. A small series of cases referred to one of the authors were also reported., Conclusions: Recommendations are made as to the prevention, acute care and subsequent investigation of adverse reactions. The most important conclusion is not to just label the response as allergic and to use an alternative agent. Detailed investigation and reporting should be made for all cases of suspected severe adverse reaction to local anaesthetic agents., (© 2011 Australian Dental Association.)

Background: Inhaled nitric oxide (iNO), commonly used for hypoxic neonates, may react with haemoglobin to form methaemoglobin (MetHb). MetHb monitoring during iNO therapy has been questioned since low doses of iNO are used., Aim: To evaluate the incidence of and identify risk factors associated with elevated MetHb in neonates treated with iNO., Methods: Neonates who were treated with iNO and had at least one MetHb measurement were included. Demographic characteristics and methods of iNO administration (dosage, duration) at the time of each MetHb measurement were analysed., Results: Four hundred and fifty-two MetHb measurements from 81 premature and 82 term and near-term infants were analysed. MetHb was above 5% in one-term infant, and between 2.5-5% in 16 infants. A higher maximum dose of iNO (22.7 vs 17.7 p.p.m.), but not gestational age, was a significant risk factor for elevated MetHb. Significantly higher oxygen levels (75.5% vs 51.7%) were associated with higher MetHb in term infants. Preterm infants had no risk for high MetHb when iNO was kept below 8 p.p.m. These data suggest the possibility of limiting blood withdrawal when low doses iNO are used., Conclusion: High MetHb is exceptional in neonates treated with low dose iNO. Associated risk factors are related to high iNO dose and the simultaneous use of high concentrations of oxygen., (© 2010 The Author(s)/Journal Compilation © 2010 Foundation Acta Paediatrica.)

Objective: The aim of this review is to warn about the effects of methemoglobin and its catabolic products and the toxic effects caused by environmental oxidants that cause high-risk pregnancy and may later impair the health of newborns, children and adolescents., Methods: In our study of pregnant women (n = 36) whose methemoglobin level was >1.5 g/l, we took blood samples from their newborns to determine the frequency of sister chromatid exchange (SCE) by cultivating lymphocytes. The research took place at the Department of Biology and Medical Genetics of the School of Medicine in Rijeka (Croatia)., Results: The results have shown that no deviation in the SCE frequency was found in either case (1990). We examined data on the health of newborns collected at perinatal hospital departments in Rijeka (Croatia), the preschool office and school service at the Labin Health Center and continued until they were 18 years of age (2008). The statistics obtained by applying the chi-square test show that the incidences of neonatal jaundice (p = 0.034), heart murmur at a later age (p = 0.011) and dyslalia and learning/memory impairments (p = 0.002) were significantly higher than in children of control mothers (n = 19)., Conclusion: Depending on the mother's exposure to environmental oxidants, during its development the fetus is more likely to be affected by methemoglobin and hemolysis. Oxidants affect the vascular endothelium of kidneys, brain and other vital organs, because they have the capacity to cross the damaged fetomaternal placental barrier. 'Fetal preeclampsia' is an expected manifestation of the condition. Our research proves our thesis on the pathophysiological relationship between methemoglobinemia and unexplained jaundice and hyperbilirubinemia, heart murmur at a later age, dyslalia and learning and memory impairments that have not exactly been demonstrated yet.

Unlabelled: Ground water is a major source of public supply for the rural population and in some areas, it is only source of available water. It is well known the toxic action of nitrate upon organisms, by formatting methemoglobin and N-nitroso compounds., Material and Methods: In this study it was investigated the presence of nitrates and nitrites in same well waters, mountain and hill areas in Neamţ district. The chemical parameters were carried out by following standard methods. The statistical analysis includes descriptive statistics of the water quality parameters., Results: It is noticed high values of the nitrate concentrations, over Maximum Admissible Concentration (MAC), explained by excessive use of agricultural synthetic fertilizer and telluric nitrogen. It was registered a number of 38 cases of methemoglobinemia in small children with artificial nutrition, all cases from hill area. The maximum methemoglobin level was 60% and the minimum value of nitrate concentration in the water samples was 396 mg NO3-/L., Conclusions: We established a direct correlation between the level of methemoglobin and the nitrate concentrations in water samples. It is recommended the use well waters with maximum 48 mg/L nitrates content.

Background: The purpose of this article is to summarize all episodes of local anesthetic-related methemoglobinemia found in the medical literature., Methods: I performed a search of the American National Library of Medicine's PubMed with the following key words: "local anesthetic" and "methemoglobinemia.", Results: Two-hundred-forty-two episodes (40.1% published in year 2000 or after) were found. Chocolate-colored blood suggests methemoglobinemia but other colors may be found. A discrepancy between the pulse oximeter saturation (< or = 90%) and the arterial oxygen partial pressure (> or = 70 mm Hg) was present in 91.8% of the episodes. The difference between oxygen saturation measured by pulse oximetry and co-oximetry varied from -6.2% to 44.7%. Plain prilocaine may induce clinically symptomatic methemoglobinemia in children older than 6 mo at doses exceeding 2.5 mg/kg. In adults, the dose of prilocaine should be kept lower than 5.0 mg/kg, which is reduced to 3.2 mg/kg in the presence of renal insufficiency and to 1.3 mg/kg if other oxidizing drugs are used concurrently. A single spray of benzocaine may induce methemoglobinemia. Clinical symptoms may be observed at relatively low methemoglobin values, including coma at 32.2 and 29.1% in children and adults, respectively. Rebound methemoglobinemia (benzocaine on mucous membranes) with methemoglobin values as high as 59.9% may occur up to 18 h after methylene blue administration. Complications of methemoglobinemia include hypoxic encephalopathy, myocardial infarction, and death., Conclusion: Benzocaine should no longer be used. Prilocaine should not be used in children younger than 6-mo-old, in pregnant women, or in patients taking other oxidizing drugs. The dose should be limited to 2.5 mg/kg.

Primaquine (PQ) is recommended to prevent relapses in patients with Plasmodium vivax malaria infection. However, treatment with PQ causes methemoglobinemia. In this study, we measured the methemoglobin (MetHB) levels in three groups of subjects who received PQ treatment at 0.58, 0.83, or 1.17 mg/kg/d. A total of 112 subjects were studied. MetHB levels were detected at > or = 4% in 46-50% 1 day after PQ treatment in all three groups and 4-9% of subjects had MetHB levels > or = 4% 15 days after treatment. Only subjects receiving the highest doses of PQ had mild and brief adverse events, and 17% of them were associated with treatment. We conclude that when PQ is administered under certain conditions (i.e., normal glucose-6-phosphate dehydrogenase activity, in non-pregnant subjects and with a light meal), daily doses as high as 1.17 mg/kg do not represent a serious risk of high MetHB levels to patients.

Context: Nitrate is ubiquitous in environmental media (air, water and soil) and other sources (some medicines, inorganic fertilizers and household's chemicals). It is a hemoglobin-oxidizing agent that can cause methemoglobinemia. The effect of nitrate on infants is well known but less is known about nitrate-induced methemoglobinemia in young children., Method: Two cross-sectional studies were carried out in Salé, Morocco to determine the prevalence of methemoglobinemia among 411 infants and children aged 1-7 years in two adjacent areas that were similar in terms of the air quality, available vegetables and medicines but different in terms of the drinking water quality (nitrate-contaminated well water versus municipal water)., Results: In the exposed area, nitrate concentration was measured in 78 wells and ranged from 15.39 to 246.90mg/l as NO3-. Nitrate levels were higher than 50mg/l in 69.2% of the surveyed wells, and 64.2% of the participants were drinking nitrate contaminated well waters. The prevalence of methemoglobinemia among study children was 36.2% in the exposed area, and 27.4% in the non-exposed area. Study children drinking well water with a nitrate concentration >50mg/l were significantly more likely to have methemoglobinemia than those drinking well water with a nitrate concentration <50mg/l (p=0.001 at 95% CI=[1.22-2.64]) or than those drinking municipal water (p<0.01 at 95% CI=[1.16-2.21]). In the exposed area, the mean methemoglobin (MetHb) level increased with age (R2= 0.79, p=0.04), whereas in the unexposed area, the mean MetHb level remained relatively stable in the first 6 years of life (R2=0.21, p=0.44). Mean MetHb was normal when the nitrate concentration in water was below 50mg/l as NO3-, and reached an abnormal level, when the nitrate concentration in water ranged between 50 and 90mg/l as NO3-. This last level was statistically similar to mean MetHb at nitrate level above 90mg/l as NO3- (up to 246.9mg/l as NO3-). No association was observed between methemoglobinemia prevalence and gender. This is the first study about methemoglobinemia conducted in Morocco.

Is nitrate harmful to humans? Are the current limits for nitrate concentration in drinking water justified by science? There is substantial disagreement among scientists over the interpretation of evidence on the issue. There are two main health issues: the linkage between nitrate and (i) infant methaemoglobinaemia, also known as blue baby syndrome, and (ii) cancers of the digestive tract. The evidence for nitrate as a cause of these serious diseases remains controversial. On one hand there is evidence that shows there is no clear association between nitrate in drinking water and the two main health issues with which it has been linked, and there is even evidence emerging of a possible benefit of nitrate in cardiovascular health. There is also evidence of nitrate intake giving protection against infections such as gastroenteritis. Some scientists suggest that there is sufficient evidence for increasing the permitted concentration of nitrate in drinking water without increasing risks to human health. However, subgroups within a population may be more susceptible than others to the adverse health effects of nitrate. Moreover, individuals with increased rates of endogenous formation of carcinogenic N-nitroso compounds are likely to be susceptible to the development of cancers in the digestive system. Given the lack of consensus, there is an urgent need for a comprehensive, independent study to determine whether the current nitrate limit for drinking water is scientifically justified or whether it could safely be raised.

Background: The potentially life-threatening condition of methemoglobinemia is characterized by cyanosis, low pulse oximetric readings, and normal arterial Po(2) values. Acquired methemoglobinemia has been linked to the use of the topical anesthetic benzocaine in endoscopic procedures, including transesophageal echocardiography (TEE). Yet, the incidence of benzocaine-induced methemoglobinemia with TEE and the clinical factors associated with its development are unclear., Methods: All cases of methemoglobinemia complicating TEE at our institution (from January 1, 1999, to July 1, 2006) were identified by a comprehensive review of medical records and echocardiography and pharmacy databases., Results: During 90 months among 28 478 TEEs, 19 cases of methemoglobinemia were identified, with a mean +/- SD methemoglobin level of 32% +/- 15%. All patients were cyanotic, with low oxygen saturations. Eighteen of 19 patients received methylene blue (mean +/- SD dose, 1.3 +/- 0.4 mg/kg of body weight), with resolution of symptoms and signs. One of 19 cases resolved spontaneously. Compared with a random sample of 190 patients undergoing TEE, the age, sex, body mass index, left ventricular systolic function, and dose of sedation (midazolam hydrochloride, fentanyl citrate, or both) were similar in the 2 groups. However, study patients who developed methemoglobinemia were more likely to be hospitalized (89.5% vs 57.6%, P =.005), be anemic (84.2% vs 44.7%, P =.002), and have active systemic infection (68.4% vs 6.8%; P < .001) at the time of TEE compared with the random control cohort., Conclusions: In a large series of patients undergoing TEE, the incidence of methemoglobinemia is low (1 case per 1499 [0.067%; 95% confidence interval, 0.040%-0.100%]) and has a good outcome if promptly recognized and treated. Clinical factors associated with the development of methemoglobinemia include sepsis, anemia, and hospitalization. Minimizing or avoiding the use of benzocaine in these patients is recommended.

Benzocaine administration to facilitate upper endoscopic procedures can result in the relatively uncommon but potentially fatal complication known as methemoglobinemia. For this reason, the Veterans Health Administration (VA) announced on February 8, 2006, that they would stop using benzocaine-containing sprays for procedures involving the mouth and throat. Methemoglobinemia should be considered in any patient who demonstrates cyanosis, respiratory distress, headache, lightheadedness, and a dark, chocolate-colored blood after receiving pharyngeal anesthesia. Prompt recognition of this rare (but potentially fatal) condition is important. Once identified, treatment is generally rapid with methylene blue. The patient should be monitored in the intensive care setting for recurrence. Knowledge of this adverse medication reaction is essential for all gastroenterology nurses.

A descriptive, cross-sectional and analytical study was carried out in 3 areas of the Gaza Strip, Palestine, in 2002, to determine the factors associated with high methaemoglobin (Met-Hb) levels in infants and the relationship with nitrate concentration in drinking water wells. Drinking water sources were likely to be the main factor for high levels of Met-Hb. Out of 338 infants attending for vaccination, having supplemental feeding, use of boiled water and age 3-6 months were associated with high Met-Hb levels. The highest mean Met-Hb level was in Khan-Younis, where the highest mean nitrate concentration was recorded in drinking water. The results emphasize the importance of exclusive breastfeeding for infants < 6 months old, and the choice of a suitable source of water for these infants.

Perambalur is the most backward district in the state of Tamil Nadu (India). It has ten unions, of which Thirumanur union has historical importance and is blessed with fertile lands. Thirumanur union has Kollidam river and Pullambadi canal as rich sources of water for irrigation. Thirumanur union has large number of Chozha temples at various places like Thirumalapadi, Periyamanai, Kamarasavalli, Thoothur, Senapathimudikondan, Kandaradhitham, Keelapalur and Melapalur. Thirumanur union being the south end union of Perambalur district, has Trichy district and Tanjore district as its neighbours. Thirumanur union has an area of 64 hectare, of which 48 hectare is under cultivating land. This union has maximum number of thirty-six villages. Though most of the villages use river water as their major source of drinking, they also use groundwater as their other source. Lot of work has been done and published already on the groundwater quality of many villages in other different unions of the Perambalur district. But in the Thirumanur union, there was need to undertake the study to assess the drinking water quality in the region. Hence, ten villages of Thirumanur union were selected, where the people use groundwater for drinking, and the water samples were subjected to systematic analysis. The depth of the bore wells varied from 100-200 feet. The values obtained for different parameters were compared with the standard values given by ISI / ICMR / WHO and the variations were notable for the parameters like nitrate and total hardness for few samples. Therefore, a medical survey was carried out to study the harmful effects on the society due to these two parameters at the villages-Keelapazhur, Palanganatham and Venganur.

Objective: This case series documents an occupational outbreak of methemoglobinemia among five steam press operators at a rubber plant. Investigative findings identified the cause as repeated exposure (through manual handling) to an adhesive containing dinitrobenzene., Results: The workers presented with yellow-stained hands and a variety of clinical manifestations. Methemoglobinemia levels obtained in the emergency room ranged from 3.8% to 41.2%. Methylthioninium chloride (methylene blue) rapidly reversed the cyanosis and alleviated associated symptoms in the rubber molding workers requiring treatment., Conclusions: Prompt action by plant officials and subsequent investigation by National Institute of Occupational Safety and Health/Occupational Safety & Health Administration personnel resulted in the timely and successful resolution of the problem. Individual presentations, assessment, and management are discussed along with recommendations for occupational investigation and referral.

Differences between children and adults with respect to exposure rates, absorption of chemicals, metabolism, and organ development make children uniquely vulnerable to environmental hazards. Moreover, biology does not exist outside of the social life of the child. At least two important implications flow from these findings. First, pediatricians must pay closer attention to the conditions of childhood and the specific details of a child's life in attempting a complete understanding of childhood diseases, particularly their sources in environmental and social conditions. At a minimum, pediatricians must inquire more carefully about environmental exposures and children's complaints in order to make accurate diagnoses. Perhaps equally critical, pediatricians must engage in more aggressive prevention efforts. While they often try to prevent exposure by educating parents about keeping household chemicals away from young children, they might likewise consider that the information they possess about children's special vulnerability to environmental risks could usefully inform political and social decisions to protect children from those risks. This includes, for example, supporting air pollution standards that are protective of children and advocating for stricter controls for certain chemicals to reduce health risks for this vulnerable group.

Background: Methemoglobinemia (MHb) is characterized by abnormal levels of oxidized hemoglobin that cannot bind and transport oxygen. When induced by benzocaine anesthetic spray and other chemicals, it can result in cyanosis and life-threatening complications., Methods: From 818 439 adverse event reports received by the US Food and Drug Administration from November 1997 through March 2002, we extracted every report for use of a benzocaine product. We classified each case by product type (eg, spray, gel, or solution), by whether MHb was involved, and by the dose given., Results: Among 198 reported adverse events of all types associated with benzocaine, 132 cases (66.7%) involved definite or probable MHb. The MHb cases included 107 serious adverse events (81.1%) and 2 deaths (1.5%). In 123 cases (93.2%), the product was a spray; in 2 cases (1.5%), a benzocaine-containing lozenge; and 1 case, a gel. In the 69 cases that specified a dose, 37 (53.6%) indicated that a single spray was applied (approximately the recommended amount)., Conclusions: Health professionals involved in endoscopy, intubation, bronchoscopy, or similar invasive procedures using benzocaine-containing sprays should know that (1) administration may cause MHb with potentially serious consequences, (2) identifying the reaction to benzocaine usually requires cooximetry (although it can be implied by symptoms), and (3) treatment involves immediate intravenous administration of 1 to 2 mg/kg of methylene blue.

The objective of this prospective study was to determine if a correlation could be established between the ground-level concentrations of sulfur dioxide and methemoglobin concentrations in pregnant women when a coal-powered thermoelectric power plant was in operation ("dirty" period) and when it was closed ("clean" period). The location of the power plant, Plomin 1, in Labin, Croatia, was taken into consideration. Blood and urine samples of each pregnant woman in the study were tested three times in the clean period (n = 138) and three times in the dirty period (n = 122), with 1 month between each test. I observed a correlation between the increase in mean values of methemoglobin and the ground-level concentration of SO(2) on corresponding dates during the dirty period (r = 0.72, p < 0.01). In the clean period, the negative mean value of methemoglobin was significant (r = -0.60, p

In 1982 and 1997 there were explosions of barley-containing silos in France, one in Metz (1982) and the other in Blaye (1997). There were a total of 25 victims, including 23 fatalities (12 in Metz and 11 in Blaye). In each case there was one survivor. This report is a retrospective study of 22 victims (11 at each site); all of them had multiple lesions due to the explosion and the immediate aftermath. The lesions demonstrated direct involvement of the blast effect associated with silo destruction, the heat from the explosion, the effects of toxic gases and asphyxia. The forensic pathologist is an important member of the emergency response team. This team has the responsibility for initially assessing the damage and for identifying the victims. The role of the forensic pathologist is therefore essential and they should be included in emergency planning to facilitate the initial assessment, shorten the time taken to identify the victims and improve safety procedures. Although dust explosions in agro-business plants are occurring more frequently, postmortem data are rare.

Benzocaine (ethyl aminobenzoate), a topical anesthetic widely used before transesophageal echocardiography, has been reported to cause acquired methemoglobinemia. The incidence of benzocaine-induced methemoglobinemia in clinical practice, however, has been difficult to estimate. After systematic review of our institutional experience for clinically recognized cases of benzocaine-induced methemoglobinemia in patients undergoing transesophageal echocardiography, we report an estimated incidence of 0.115% (95% confidence interval 0.037-0.269). This report also provides the largest analysis of the incidence of methemoglobinemia in readministration cases. Although controversy remains as to whether this is an idiosyncratic versus dose-related response, a description of purported patient risk factors is included.

In this nested case-control study, we investigated the risk factors for methemoglobinemia (MHG) in 71 children in the Transylvania region of Romania. This study was unique in that the exposures for cases and controls were calculated as continuous values and were reported in milligrams per kilogram per day of nitrate/nitrite based on careful dietary reconstruction and environmental sampling. This procedure allowed us to compare point estimates of nitrate/nitrite exposure with other continuous, categoric, and ranked risk factors such as the presence or absence of diarrheal disease, reported severity of diarrheal disease, the use of vitamin supplements, the presence, absence, and/or duration of breast-feeding, and whether or not first-generation relatives experienced MHG. Analysis of these factors and exposure levels using both univariate and multivariate whole-model tests was performed to understand the relative significance of risk factors at varying levels of exposure to the development of MHG. Univariate and multifactorial analysis of risk factors for MHG underscored that, for this population, MHG is most strongly associated with nitrate/nitrite exposure through the dietary route (p = 0.0318), via feeding of formula and tea made with water containing high levels of nitrates, and that breast-feeding protects infants younger than 6 months of age (p = 0.0244). Our findings also raise questions about the role of diarrheal disease in the development of MHG, as likelihood ratios (likelihood 4.323, p = 0.0376) and multifactorial analysis indicated a significant role for diarrheal disease for some individuals.

Aims: The primary focus of this exposure assessment work involved developing an exposure model and determining a numerical point estimate of the amount of biologically relevant nitrate/nitrite exposure that occurred for each child in the study. This assessment was done in support of two epidemiological studies. The first study was an epidemiological cohort study (three cohorts based on nitrate/nitrite exposure) that explored the relationship between high nitrate/nitrite exposure and neuropsychological development. The second study was a nested case/control study (cases of methemoglobinemia versus disease-free controls) that sought to explore the relationship between MHG and various risk factors for the disease., Methods: This work uses both dietary survey and environmental sampling and modeling in order to develop two point estimates of nitrate exposure in milligrams per kilogram per day of nitrite (the biologically active form of the hemoglobin-oxidizing agent) for the first 6 months of the child's life (2-months-of-age and 6-months-of-age point estimates). Methodologies included proxy interviews of primary caregivers, review of existing medical and environmental sampling and analysis., Results: Exposure to nitrate--nitrogen (with final calculations converted to the biologically active form of the toxin, nitrite) was categorized as high, medium, and low as determined from the distribution of the data derived from final exposure calculations at both the 2-months-of-age point estimate and at the 6-months-of-age point estimate. These tertiles correspond to greater-than-or-equal1.5 mg/kg/day nitrite-nitrogen for high-exposure individuals, <1.5-> or = 0.1 mg/kg/day for medium-exposure individuals, and <0.1 mg/kg/day for low-exposure individuals. Analyses illustrate that over 90% of the nitrate exposure occurred through the consumption of liquids (water) at the 2-months-of-age point estimate while at the 6-months-of-age point estimate, a 10-fold change in the amount of solid consumables occurred., Conclusions: Final exposure calculations were well differentiated into three tertiles based on a point estimate of average daily intake of nitrite in milligrams per kilogram body weight per day at roughly 2 and 6 months of age. These categories of exposure, based on the exposure model point estimate, correspond well with the exposure estimates as estimated only on the basis of cohort status and their corresponding nitrate/nitrite well water levels. Comparisons of these two sets of data illustrate that following the MHG incident, Cohort II shifted places with Cohort I to become the high-exposure cohort. Further, the predictive ability of the exposure assessment in regard to the outcome of MHG was estimated using a Likelihood Ratio and Pearson's Crosstab analysis. This was performed on the 2-month-of-age point estimate. Likelihood Ratio and Pearson's chi-square were 39.40 and 33.74, respectively, with a probability of achieving these fits by chance alone of <0.0001. This indicates clearly that the children who experienced MHG were also the children at the 2-month-of-age point estimate who had received the highest exposure to nitrate/nitrite through their diet.

Objective: To assess clinical and epidemiologic data of 7 infants diagnosed with acquired methemoglobinemia at the pediatric emergency department between 1993 and 1998. All cases were attributed to the consumption of mixed vegetables., Methods: Medical records were reviewed to collect anamnestic data; history of food ingestion; and results of physical examination, pulse oximetry, gasometry, cooximetry, urinalysis, and outcome. Local health authorities provided information on nitrate concentration in running water and in vegetables of common consumption in the area., Results: The mean age of the patients was 8.14 months (range: 7-13). None of the infants was undernourished, had diarrhea, or was given any drug. Drinking water showed a nitrate concentration of 3 to 6 ppm. All were fed homemade purée of mixed vegetables, prepared in advance and kept in the refrigerator for 12 to 27 hours. Silver beets were a common ingredient. No case showed metabolic acidosis. Methemoglobin level ranged between 10% and 58%. Three cases had nitrituria. Silver beets in our area were the vegetables with the highest nitrate concentration (mean: 3200 mg/kg)., Conclusions: Consumption of silver beets and incorrect storage of homemade purées of mixed vegetables were potential causes of methemoglobinemia in this series. The disease may occur in children older than 6 months of age. Nitrituria in a cyanotic infant may suggest the diagnosis of methemoglobinemia.methemoglobinemia, nitrates, nitrites, food analysis, infant food, food preservation.

This study analyses retrospectively some of the risks associated with the use of WHO-multidrug therapy (MDT) in Sri Lanka. Case records of 3,333 new cases of leprosy attending the Central Leprosy Clinic in Colombo during 1991-1995, were analysed for adverse drug reactions involving the liver and blood. There were 81 reports of suspected hepatic or haematological adverse reactions associated with the use of MDT, of which 39 were classified as haemolytic anaemia, 25 as toxic hepatitis, 2 as methaemoglobinaemia and 15 as anaemia. Dapsone, was incriminated in the majority of adverse reactions (72%). Adverse drug reactions were more common in female than male subjects (55% vs 45%; P < 0.5), but there was no significant differences between the age groups. Majority of adverse reactions was seen within the first three months of initiation of MDT. This study in no way undermines the benefits of MDT but highlights the risks and suggests measures to minimize these risks.

Methemoglobinemia is a serious medical condition that affects hundreds of infants in the United States each year. The condition involves the oxidation of red cell hemoglobin to a state that is unable to transport oxygen. Affected infants appear cyanotic and may have altered mental status. The condition is readily reversible if recognized and treated appropriately. The Wisconsin Division of Public Health investigates all cases of infant methemoglobinemia in an attempt to determine their cause. Between January 1990 and September 1999, 8 infants were diagnosed with this condition. Review of their hospitalization records found that 3 of these cases involved infants whose formula was prepared with water from nitrate-contaminated wels. Risk factors identified in the remaining cases included use of folk remedies, misuse of over-the-counter analgesics, and an inherited enzyme deficiency. Causes were not identified for 2 of the cases. All of the affected infants recovered.

Five cases of methaemoglobinaemia, following exposure to industrial waste, are examined, investigated and managed successfully. The condition is discussed in detail.

On rare occasions benzocaine has produced methemoglobinemia from oral, rectal and dermal exposures. There is disagreement whether this is an idiosyncratic event or a dose-related event. To gain a better perspective on this problem we retrospectively reviewed cases at 4 large regional poison centers of children <18-y of age from 1993-1996. One hundred and eighty-eight benzocaine exposures were reported. Mean and median ingested dosage were 86.8 (+/- 89.5) mg/kg and 50 mg/kg, respectively. Fifty-eight patients (30%) were managed in the emergency department; 8 patients had methemoglobin levels determined. One child had a methemoglobin level of 19%; all others were <1%. One hundred and seventy-three patients (92%) remained asymptomatic. Other symptoms were minor: oral numbness (8), vomiting (3), and 1 each of oral irritation, dizziness and nausea. In this series of accidental ingestions of benzocaine-containing products cyanosis was rare and apparently not dose related. These cases may be safely managed at home with telephone follow up for at least 2 h. If there is evidence of cyanosis, dusky pallor, shortness of breath, or change in mental status direct medical evaluation should be recommended.