Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0231835 (tachypnea)
 2,543 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathophysiology, clinical features, and management of cyanide toxicity are reviewed and sources of cyanide are listed. Cyanide is a deadly poison that is found in many foods and household and industrial products, including some that are readily available. Cyanide binds with cytochrome oxidase, the enzyme responsible for oxidative phosphorylation, and paralyzes cellular respiration. Because the tissues cannot use oxygen that is delivered, aerobic metabolism ceases. The signs and symptoms of cyanide poisoning reflect the extent of cellular hypoxia. Manifestations may include respiratory abnormalities (progressing from tachypnea and dyspnea to respiratory depression and apnea), hemodynamic instability, metabolic acidosis, and, possibly, local irritant effects after oral ingestion of cyanide. The mainstays of therapy are 100% oxygen and specific antidotes to cyanide. Sequential treatment with amyl nitrite by inhalation, intravenous sodium nitrite 3%, and intravenous sodium thiosulfate 25% is directed toward decreasing the amount of cyanide available for cellular binding. Nitrites convert hemoglobin to methemoglobin, which reacts with cyanide to form cyanomethemoglobin. Sodium thiosulfate serves as a source of sulfur groups, which are needed for conversion of cyanide to thiocyanate, a compound that is relatively less toxic and is excreted renally. Supportive care also is important. Cobalt EDTA, hydroxocobalamin, and aminophenols have also been used but are not considered standard treatments. Cyanide poisoning is a medical emergency that requires prompt recognition and immediate and aggressive treatment.
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PMID:Clinical features and management of cyanide poisoning. 353 Jun 15

Nitromethane is used as a rocket and engine fuel; as a synthesis intermediate for agricultural fumigants, biocides, and other products; as a solvent; and as an explosive in mining, oil-well drilling, and seismic exploration. It has been detected in air, in surface and drinking water, and in cigarette smoke. Nitromethane was studied because of the potential for widespread human exposure and because it is structurally related to the carcinogens 2-nitropropane and tetranitromethane. Male and female F344/N rats and B6C3F1 mice received nitromethane (purity 98% or greater) by inhalation for 16 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and peripheral blood erythrocytes of mice. 16-DAY STUDY IN RATS: Groups of five male and five female rats were exposed to 0, 94, 188, 375, 750, or 1,500 ppm nitromethane by inhalation, 6 hours per day, 5 days per week, for 16 days. All rats survived until the end of the study. The mean body weight gain of male rats in the 1,500 ppm group was slightly but significantly less than that of the controls; the final mean body weights and mean body weight gains of exposed females were similar to those of the controls. Clinical findings in all male and female rats in the 1,500 ppm groups included increased preening, rapid breathing, hyperactivity early in the study, and hypoactivity and loss of coordination in the hindlimbs near the end of the study. The relative liver weights of all exposed groups of male rats and the absolute and relative liver weights of females exposed to 375 ppm or greater were significantly greater than those of the controls. Minimal to mild degeneration of the olfactory epithelium was observed in the nose of males and females exposed to 375 ppm or greater. Sciatic nerve degeneration was present in all male and female rats exposed to 375 ppm or greater; rats exposed to 750 or 1,500 ppm also had reduced myelin around sciatic axons. 16-DAY STUDY IN MICE: Groups of five male and five female mice were exposed to 0, 94, 188, 375, 750, or 1,500 ppm nitromethane by inhalation, 6 hours per day, 5 days per week, for 16 days. All mice survived to the end of the study. The final mean body weights and weight gains of exposed males and females were similar to those of the controls. Clinical findings included hypoactivity and tachypnea in male and female mice in the 1,500 ppm groups. Absolute and relative liver weights of male mice in the 750 and 1,500 ppm groups and female mice in all exposed groups and the relative liver weight of males in the 375 ppm group were significantly greater than those of the controls. Degeneration of the olfactory epithelium of the nose was observed microscopically in all males and females exposed to 375 ppm or greater; this lesion was of minimal severity in males and minimal to mild severity in females. 13-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were exposed to 0, 94, 188, 375, 750, or 1,500 ppm nitromethane by inhalation, 6 hours per day, 5 days per week, for 13 weeks. All rats survived to the end of the study. The final mean body weight and weight gain of male rats in the 1,500 ppm group were significantly less than those of the controls. Clinical findings included hindlimb paralysis in rats in the 750 and 1,500 ppm groups. Inhalation exposure of rats to nitromethane resulted in an exposure concentration-dependent, microcytic, responsive anemia; anemia was most pronounced in males and females exposed to 375 ppm or greater. The presence of schistocytes, Heinz bodies, and spherocytes and increased mean cell hemoglobin concentration and methemoglobin concentration were evidence that a hemolytic process was occurring; this hemolytic process could have accounted, in part, for the anemia. Thrombocytosis accompanied the anemia and would be consistent with a reactive bone marrow or could have been due to the erroneous inclusion of small erythrocyte fragments as part of the platelet count. On day 23, transient decreases in serum triiodothyronine, thyroxine, and fr and free thyroxine were observed in male rats exposed to 375 ppm or greater and female rats exposed to 750 or 1,500 ppm. There was little or no pituitary response to the thyroid hormone decreases, as evidenced by the lack of significantly increased concentrations of thyroid-stimulating hormone in exposed rats. No biologically significant differences in organ weights were observed. The forelimb and hindlimb grip strengths of males in the 1,500 ppm group were significantly less than those of the controls. The hindlimb grip strengths of females in the 750 and 1,500 ppm groups were also significantly less than the control value. Minimal to mild hyperplasia of the bone marrow was observed microscopically in male rats in the 750 and 1,500 ppm groups and in females exposed to 188 ppm or greater. Nasal lesions in exposed males and females included olfactory epithelial degeneration in males and females exposed to 375 ppm or greater and in one female exposed to 188 ppm and respiratory epithelial hyaline droplets and goblet cell hyperplasia in males and females in the 750 and 1,500 ppm groups; the severity of nasal lesions in males and females was minimal to mild. Males and females exposed to 375 ppm or greater had minimal to mild degeneration of the sciatic nerve and the lumbar spinal cord. 13-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were exposed to 0, 94, 188, 375, 750, or 1,500 ppm nitromethane by inhalation, 6 hours per day, 5 days per week, for 13 weeks. All mice survived to the end of the study. The final mean body weights and weight gains of exposed mice were generally similar to those of the controls. There were no treatment-related clinical findings. The absolute right kidney weights of all groups of exposed male mice except the 1,500 ppm group and of females exposed to 188 ppm or greater and the relative right kidney weights of all groups of exposed males and of females in the 750 and 1,500 ppm groups were significantly greater than those of the controls. The absolute liver weight of male mice in the 750 ppm group and the relative liver weights of males exposed to 375 ppm or greater were significantly greater than those of the controls. Olfactory epithelial degeneration and respiratory epithelial hyaline droplets were observed microscopically in all male and female mice exposed to 375 ppm or greater. Degeneration also occurred in females in the 188 ppm group, and hyaline droplets occurred in females in the 94 and 188 ppm groups. The average severity of the nasal lesions ranged from minimal to mild in males. In females, the average severity of olfactory epithelial degeneration ranged from minimal to mild and the severity of respiratory epithelial hyaline droplets ranged from minimal to moderate. All males and nine females in the 1,500 ppm groups also had minimal extramedullary hematopoiesis of the spleen. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were exposed to 0, 94, 188, or 375 ppm nitromethane by inhalation, 6 hours per day, 5 days per week, for 103 weeks. Survival,Body Weights, and Clinical Findings: There were no significant differences in survival rates between exposed and control male or female rats. The mean body weight of females in the 375 ppm group was slightly greater than that of the control group; the mean body weights of exposed males were generally similar to the mean body weight of the controls throughout the study. Clinical findings were consistent with incidences of mammary gland neoplasms in females exposed to 188 or 375 ppm; no hindlimb paralysis, as occurred in rats in the 13-week study, was observed in male or female rats in the 2-year study. Pathology Findings: The incidences of mammary gland fibroadenoma and fibroadenoma, adenoma, or carcinoma (combined) in female rats in the 188 and 375 ppm groups were significantly greater than those in the controls. Additionally, the incidences of mammary gland carcinoma in the 375 ppm group were significantly greater than those in the controls. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were exposed to 0, 188, 375, or 750 ppm nitromethane by inhalation, 6 hours per day, 5 days per week, for 103 weeks. Survival,Body Weights, and ClinicalFindings The survival rate of females in the 750 ppm group was marginally greater than that of the controls. The mean body weights of exposed females were generally slightly greater than the mean body weights of the controls during the study but were generally similar to the mean body weight of the controls at the end of the study. The mean body weights of exposed males were similar to those of the controls throughout the study. Clinical findings included swelling around the eyes and exophthalmos in exposed males and females; these findings were coincident with harderian gland neoplasms. Pathology Findings: The incidences of harderian gland adenoma and adenoma or carcinoma (combined) in exposed mice increased with increasing exposure concentration and were significantly greater in males and females in the 375 and 750 ppm groups than those in the controls. The incidences of harderian gland carcinoma in males and females in the 375 and 750 ppm groups were also slightly greater than those in the controls. Female mice in the 188 and 750 ppm groups had significantly greater incidences of hepatocellular adenoma and hepatocellular adenoma or carcinoma (combined) than the controls. The incidences of liver eosinophilic focus increased with increasing exposure concentration, and the incidences in the 375 and 750 ppm groups were significantly greater than the control incidence. The incidences of alveolar/bronchiolar carcinoma in male mice in the 750 ppm group and female mice in the 375 ppm group were significantly greater than those in the controls. Females in the 750 ppm group also had a significantly greater incidence of alveolar/bronchiolar adenoma or carcinoma (combined) and a slightly greater incidence of alveolar/bronchiolar adenoma than the controls. Females in the 375 ppm group had a significantly greater incidence of cellular infiltration of histiocytes in the lung than the controls. The incidences of degeneration and metaplasia of the olfactory epithelium and hyaline degeneration of the respiratory epithelium were significantly greater in exposed male and female mice than those in the controls. Additionally, males in the 375 and 750 ppm groups had significantly greater incidences of inflammation of the nasolacrimal duct than did the controls. GENETIC TOXICOLOGY: Nitromethane was not mutagenic in any tests performed by the NTP. It did not induce mutations in Salmonella typhimurium, with or without S9 metabolic activation, and no induction of sister chromatid exchanges or chromosomal aberrations in cultured Chinese hamster ovary cells exposed to nitromethane was noted with or without S9. No increase in the frequency of micronucleated erythrocytes was observed in peripheral blood samples of male and female mice at the end of the 13-week inhalation study of nitromethane. CONCLUSIONS: Under the conditions of these 2-year inhalation studies, there was no evidence of carcinogenic activity of nitromethane in male F344/N rats exposed to 94, 188, or 375 ppm. There was clear evidence of carcinogenic activity of nitromethane in female F344/N rats based on increased incidences of mammary gland fibroadenomas and carcinomas. There was clear evidence of carcinogenic activity of nitromethane in male B6C3F1 mice based on increased incidences of harderian gland adenomas and carcinomas. There was clear evidence of carcin ogenic activity in female B6C3F1 mice, based on increased incidences of liver neoplasms (primarily adenomas) and harderian gland adenomas and carcinomas. Increased incidences of alveolar/bronchiolar adenomas and carcinomas in male and female mice exposed to nitromethane were also considered to be related to chemical administration. Exposure to nitromethane by inhalation for 2 years resulted in increased incidences of nasal lesions including degeneration and metaplasia of the olfactory epithelium and degeneration of the respiratory epithelium in male and female mice. Synonym: Nitrocarbol
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PMID:NTP Toxicology and Carcinogenesis Studies of Nitromethane (CAS No. 75-52-5) in F344/N Rats and B6C3F1 Mice (Inhalation Studies). 1258 15

OBJECTIVE: To study the changes in methemoglobinemia of 17 children admitted with acute exposure to dapsone complicated by a methemoglobin concentration greater than 20% of the total hemoglobin. The children were treated with multiple doses of activated charcoal with or without the administration of methylene blue.PATIENTS AND METHODS: Seventeen patients (ages 1-13 y, median 3 y), were admitted 1-72 h after the ingestion of 100-1200 mg (median 350 mg, 10 patients) or an unknown amount of dapsone (7 patients). The methemoglobin blood concentrations upon admission ranged from 23.5%-49.7% (median 37.8%), and the main clinical features were cyanosis (17), tachycardia (17), vomiting (11) and tachypnea (8). All of the children received multiple doses of activated charcoal orally or via nasogastric tube (1g/kg, 10% solution, 4-6 times/day, 3-16 doses with a median of 8 doses). Twelve of the 14 patients with methemoglobin levels greater than 30% were also treated with a single dose of methylene blue (1-2% solution, 1-2 mg/kg) infused IV over 5 min.RESULTS: There was a progressive decrease in the methemoglobin levels after the beginning of both treatments (multiple doses of activated charcoal alone or associated with methylene blue), and only one dose of methylene blue was necessary. There were no significant statistical differences between the results of the two treatments according to the time-course decrease in methemoglobinemia (p=0.49 Wilcoxon test).CONCLUSIONS: Multiple doses of activated charcoal given when methemoglobin levels were greater than 20% can be considered as a possible treatment for pediatric patients, with or without the administration of methylene blue, after acute dapsone exposure.
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PMID:[Acute dapsone exposure and methemoglobinemia in children: treatment with multiple doses of activated charcoal with or without the administration of methylene blue] 1464 58

This report describes a case of methemoglobinemia in association with dapsone therapy. The patient, an immunocompromised child with chronic immune thrombocytopenic purpura, presented with fever, cough, perioral cyanosis, bilateral lower lobe rales, and low O2 saturation by pulse oximetry (89%). His medications included prednisone and rituximab for chronic immune thrombocytopenic purpura, and dapsone for Pneumocystis carinii pneumonia prophylaxis. Because of his lack of dyspnea and tachypnea, and the temporal association of his perioral cyanosis with the initiation of dapsone therapy, a methemoglobin (MetHb) level was obtained and found to be elevated at 9.6%. The authors discuss the mechanism and treatment of methemoglobinemia secondary to dapsone. They also stress the importance of monitoring for signs and symptoms of methemoglobinemia in immunocompromised patients on dapsone therapy for P. carinii pneumonia prophylaxis.
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PMID:Methemoglobinemia associated with dapsone therapy in a child with pneumonia and chronic immune thrombocytopenic purpura. 1679 11

The patient is a young infertile lady with right tubal block on hysterosalpingogram was subjected for diagnostic hysterolaparoscopy.Hysterolaparoscopy findings were normal. Transcervical chromopertubation was performed using 20 -30 ml of diluted methylene blue through hysterosalpingogram cannula. Hesitant flow of dye was noted on left side after 2-3 flushing attempts. Ampullary block noted on right side with no spillage of the dye. Patient made an uneventful anaesthetic recovery. Five hours later patient developed tachypnea,hypotension and bluish colored urine was drained. She was shifted to ICU and patient eventually recovered after hemodynamic support with oxygen, steroids and inotropes. Spectrophotometric analysis showed methemoglobin levels of 26.3%. This case is reported for its rare but potentially fatal complication of pulmonary oedema following methylene blue. In this case pulmonary oedema manifested late in the postoperative period compared to other reported cases in the literature where pulmonary oedema was seen during intraoperative period.
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PMID:A Rare Case of Delayed Pulmonary Oedema due to Methemoglobinemia Following Laparoscopic Chromopertubation with Methyleneblue. 2512 Oct 35

A juvenile male mixed breed dog was presented for lethargy, exercise intolerance, and aggression when touched on the head. Cyanosis, tachycardia, and tachypnea were observed and persisted during oxygen supplementation. Arterial blood gas analysis by co-oximetry identified an increased methemoglobin concentration (27%; normal, <2%) with normal arterial oxygen tension. The methemoglobinemia and associated clinical signs resolved after administration of methylene blue (1 mg/kg) IV, and the dog was discharged. The affected dog's whole-genome sequence contained 2 potentially causal heterozygous CYB5R3 missense mutations suggesting that cytochrome b5 reductase deficiency was responsible for the methemoglobinemia. This hypothesis was confirmed by enzyme analysis that identified cytochrome b5 reductase activity in the affected dog's erythrocytes to only approximately 6% of that in a control sample. Clinical signs recurred 11 days after discharge but normalized and the methemoglobin concentration decreased with methylene blue administration PO (1.5 mg/kg, initially daily and then every other day).
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PMID:Long-term Treatment with Methylene Blue in a Dog with Hereditary Methemoglobinemia Caused by Cytochrome b5 Reductase Deficiency. 2896 29