Gene/Protein Disease Symptom Drug Enzyme Compound
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Acute dapsone poisoning is rare and such cases are either accidental or suicidal. Though accidental DDS poisoning are reported in children, the same is fairly uncommon in adults. Only 2 such cases are reported in India literature. We here report 4 cases of fatal sucidial DDS poisoning in adults resulting death in 3 cases. The reported acute symptoms include nausea, vomiting, hyperexcitability followed by depression, Carpopedal spasm or convulsions. The most marked signs are dyspnoea and cyanosis. The symptoms are due to methaemoglobinaemia, and or sulphaemoglobinaemia. Normally dapsone induces red cell haemolysis and even with small therapeutic doses of 25-100 mg per day, and in toxic doses reduces the oxygen carrying capacity of blood and damages the red cells making them more vulnerable for haemolysis. The peculiarity of the presentation in this series are manifestation of severe haemorrhagic episode in one case and progressive jaundice in another besides cyanosis. None of the cases had carpopedal spasm or convulsion. Out of four cases three died inspite of intensive care, intravenous vitamin C, exchange transfusion (2 cases) and other supportive measures. Intravenous methylene blue could not be used in these cases due to non-availability.
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PMID:Acute fatal DDS poisoning. (Report of 4 cases). 48 Sep 16

Dapsone (4-4-diaminodiphenyl-sulfone) is a member of the sulfone group of antibiotics used in the treatment of leprosy and various dermatitidies and more recently employed in the management of local reactions to the bite of the brown recluse spider, Loxosceles reclusa. A dapsone hypersensitivity syndrome, consisting of fever, headache, nausea, vomiting, lymphadenopathy, hepatitis, hemolysis, leukopenia, and mononucleosis, has been described in patients treated with the drug for leprosy. A case report of the hypersensitivity syndrome occurring in a patient being treated with dapsone for a brown recluse spider bite is presented.
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PMID:Case report: dapsone hypersensitivity syndrome associated with treatment of the bite of a brown recluse spider. 319 22

Dapsone has been used since 1976 in the treatment of relapsing polychondritis. A critical analysis of its therapeutic effectiveness based on 2 personal cases and 14 cases reported in the literature, all treated with dapsone alone, showed that treatment had to be discontinued in 4 on account of side effects (haemolytic anaemia, erythema multiforme, somnolence, headache, nausea); 1 patient showed no improvement and 5 relapsed; 6 responded favourably and without relapse during a 3 months' to 4 years' follow-up. Considering the unpredictable course of relapsing polychondritis and the fact that some of its clinical manifestations, notably auricular chondritis, may spontaneously resolve, the response of the disease to dapsone is difficult to establish and requires to be confirmed by a controlled clinical trial.
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PMID:[Chronic atrophic polychondritis. Critical analysis of the therapeutic efficacy of dapsone. 2 cases]. 623 76

A case of acute Dapsone intoxication due to voluntary ingestion of 3 g of this drug as a suicide attempt is described. A severe methemoglobinemia developed, accompanied by intense cyanosis, dyspnea, headache, and nausea. Subsequently, significant sulfhemoglobinemia responsible for prolonged cyanosis was observed, as well as mild hemolytic anemia. Relapses of methemoglobinemia after methylene blue treatment required repeated administration of the reducing agent. The need of a careful follow-up for several days in this type of intoxication is emphasized.
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PMID:Delayed sulfhemoglobinemia after acute dapsone intoxication. 715 40

In normal erythrocytes, small quantities of methaemoglobin are formed constantly and are continuously reduced, almost entirely by the reduced nicotine adenine dinucleotide (NADH) diaphorase system, rather than the reduced nicotine adenine dinucleotide phosphate (NADPH) diaphorase system. Methaemoglobinaemias are usually the result of xenobiotics, either those that may directly oxidise haemoglobin or those that require metabolic activation to an oxidising species. The most clinically relevant direct methaemoglobin formers include local anaesthetics (such as benzocaine and, to a much lesser extent, prilocaine) as well as amyl nitrite and isobutyl nitrite, which have become drugs of abuse. Indirect, or metabolically activated, methaemoglobin formation by dapsone and primaquine may cause adverse reactions. The clinical consequences of methaemoglobinaemia are related to the blood level of methaemoglobin; dyspnoea, nausea and tachycardia occur at methaemoglobin levels of > or = 30%, while lethargy, stupor and deteriorating consciousness occur as methaemoglobin levels approach 55%. Higher levels may cause cardiac arrhythmias, circulatory failure and neurological depression, while levels of 70% are usually fatal. Cyanosis accompanied by a lack of responsiveness to 100% oxygen indicates a diagnosis of methaemoglobinaemia, which should be confirmed using a CO-oximeter. Pulse oximeters do not detect methaemoglobin and may give a misleading impression of patient oxygenation. Methaemoglobinaemia is treated with intravenous methylene blue (methyl-thioninium chloride; ;1 to 2 mg/kg of a 1% solution). If the patient does not respond, perhaps because of glucose-6-phosphate dehydrogenase (G6PD) deficiency or continued presence of toxin, admission to an intensive care unit and exchange transfusion may be required. Dapsone-mediated chronic methaemoglobin formation can be reduced by coadministration of cimetidine to aid patient tolerance. Increasing knowledge and awareness of drug-mediated acute methaemoglobinaemia among physicians should lead to prompt diagnosis and treatment of this potentially life-threatening condition.
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PMID:Drug-induced methaemoglobinaemia. Treatment issues. 882 17

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication after solid organ transplantation. An elevated serum lactate dehydrogenase (LDH) is a marker of PTLD activity. We report the case of a 58-year-old female renal transplant patient with a prior history of extranodal PTLD, which developed 19 years after a second transplant. She was successfully treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) and maintained subsequently on sirolimus and prednisone. She presented 3 years later with fever, dyspnea, cough, lung infiltrates and elevated serum LDH concerning for recurrence of PTLD. Bronchoscopy revealed Pneumocystis carinii (jiroveci) pneumonia. The patient was treated with trimethoprim-sulfamethoxazole, but developed nausea and was converted to dapsone. The patient was readmitted 4 weeks later with increasing dyspnea and hypoxemia and found to have a methemoglobin level of 16%. Dapsone was discontinued with resolution of all symptoms. We discuss the diagnostic and clinical challenges in this complex case.
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PMID:Didactic lessons from the serum lactate dehydrogenase posttransplant: a clinical vignette. 1829 52

Dapsone has potent anti-inflammatory effects, and is used in the treatment of leprosy, cutaneous vasculitis, neutrophilic dermatoses, and dermatitis herpetiformis and other blistering disorders. However, it may cause severe adverse reactions such as hypersensitivity syndrome, which is characterized by fever, skin rash, hepatitis and lymphadenopathy. We report a 44-year-old female Korean patient with dapsone hypersensitivity syndrome (DHS) that presented as a bullous skin eruption. The patient had a 1-year history of urticarial vasculitis, treated with antihistamines, prednisolone and dapsone. Although the skin lesions improved, she reported fever, nausea, abdominal pain, jaundice, fatigue and skin rashes. On physical examination, there were generalized erythematous macules and purpura with facial oedema that developed into vesicles on the upper limbs. Histological examination of a skin biopsy of a vesicular lesion found subepidermal oedema with a mixed inflammatory cell infiltrate, including eosinophils in the dermis. Indirect immunofluorescence testing using normal foreskin as substrate revealed IgG deposits in the basement membrane zone. Circulating autoantibodies against antigens of 190 and 230 kDa were found by immunoblotting analysis using epidermal extracts. This case illustrates DHS with the formation of circulating autoantibodies.
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PMID:Dapsone hypersensitivity syndrome with circulating 190-kDa and 230-kDa autoantibodies. 1977 10

Epidemics of Dengue fever (DF) and Dengue hemorrhagic fever (DHF) are common in Southeast Asia. DF is defined & classified according to WHO criteria. Variable clinical manifestations of DF & DHF have been described in earlier studies. But some patients present with unusual clinical features and clinical profile not classifiable according to the present WHO criteria. Some of these complications if not recognized early and treated properly can even prove fatal. So this study was done to describe various clinical features in Dengue fever with special emphasis on unusual manifestations. This study was conducted at University College of Medical Sciences and associated Guru Teg Bahadur hospital; a tertiary care hospital, located in East Delhi in India. It was a retrospective study of 76 patients of probable DF; including 4 cases of DHF (according to WHO classification); 60 males & 16 females above 12 years of age admitted in medical wards of Guru Teg Bahadur hospital in an outbreak of DF which occurred during September-December 2009. The data obtained was analyzed to see clinical and laboratory profile of DF/DHF with special emphasis on unusual manifestations. The mean age of the patients was 28 +/- 9.6 years. Fever was present in all the cases with an average duration of fever being 5.47 +/- 2.2 days with body ache, (84.2%), vomiting (61.8%), abdominal pain (51.3%) and headache (19.7%) being the other presenting complaints. Hemorrhagic manifestations in the form of gum bleeding and epistaxis (35.5%), positive tourniquet test (27.6%); skin rashes (15.8%), melena (15.8%) and hematemesis (5.26%) were also present. In our study a fair no of patients presented with unusual symptoms like pain in abdomen 39 (51.3%), nausea 32 (42.1%), & vomiting 47 (61.8%), which is higher than that reported previous outbreak. Of the 39 patients who presented with abdominal pain; ultrasonography of abdomen was done in 25 patients. Fifteen (38%) of these were found to have acalculous cholecystitis. Amongst the known manifestations of DF, abdominal pain has been well described, but acalculous cholecystitis as a cause of abdominal pain is scantly reported. Another unusual manifestation was the presentation of patients (7.89%) in circulatory failure without the evidence of plasma leakage and not fulfilling all the criterion proposed by WHO for DHF/DSS. All of the above patients had very low platelet counts & tourniquet test was positive in all these six patients. Hepatomegaly and splenomegaly were observed in 34.2% and 7.89% of cases, respectively. Renal dysfunction was observed in 13.1% of cases. Laboratory investigations revealed thrombocytopenia (with a platelet count of < 100,000/microl) in all cases. Leucopenia (WBC < 4,000/mm2) and Hemoconcentration (Hct > 20% of expected for age and sex) were found in 38% and 5.26% of the cases, respectively. Results of our study indicate that apart from usual manifestations, sometimes unusual but clinically extremely important manifestations can occur which if not detected early can prove fatal. So a vigilant and timely approach is warranted.
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PMID:Unusual manifestations in dengue outbreak 2009, Delhi, India. 2247 Nov 94

This retrospective study was conducted to assess the differences in clinical features between children and adults with dengue hemorrhagic fever/ dengue shock syndrome (DHF/DSS) admitted to Ratchaburi Hospital, Ratchaburi Province, Thailand. A total of 273 patients with DHF/DSS admitted to Ratchaburi Hospital during January 2007 to May 2008 were included in the study. The median age (range) of studied subjects was 16 years (6 months to 62 years) and the ratio of adults to children was 1.6:1. Forty-eight percent of subjects were 16-30 years old. The common signs, symptoms and clinical features were: nausea/vomiting (74.0%), a positive tourniquet test (73.0%), anorexia (67.0%), hemoconcentration (58.0%), headache (54.0%), abdominal tenderness (43.0%), myalgia (39.0%) and pleural effusion (20.0%). Children had anorexia, a positive tourniquet test, abdominal tenderness and a convalescent rash more frequently than adults. Children also had significantly more prominent plasma leakage as shown by lower serum albumin and sodium and a higher prevalence of pleural effusion, ascites and shock. Although not statistically significant, the prevalence of bleeding in children was higher than in adults but more adults needed blood transfusion. This study provides additional insight into the clinical picture of DHF/DSS in adults and children and may be beneficial for clinicians caring for these adults and children.
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PMID:Differences in clinical features between children and adults with dengue hemorrhagic fever/dengue shock syndrome. 2443 12

Dapsone hypersensitivity syndrome (DHS) is a rare adverse effect of the commonly prescribed drug dapsone. We present a case of a 35-year-old male who was referred to us from the gastroenterologist with complaints of rash, nausea, vomiting, and jaundice since 2 days with a provisional differential diagnosis of infectious mononucleosis or viral exanthema. On enquiry patient gave history of taking dapsone a week prior for refractory urticaria. After thorough investigations we diagnosed him with DHS. This syndrome occurs in a relatively small proportion of patients, but it is associated with considerable morbidity and mortality. The reason for presenting this case is to remind physicians of the unpredictability and potential severity of this reaction which makes it a major concern in clinical practice.
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PMID:Mononucleosis-like drug rash: an interesting case presentation. 2479 Dec 43


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