Gene/Protein Disease Symptom Drug Enzyme Compound
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Diaminodiphenyl sulphone (dapsone) is a drug of choice in the treatment of leprosy. It is also useful for the treatment of many neutrophilic and other dermatoses. Dapsone hypersensitivity syndrome is a rare but well recognized serious adverse effect characterized by fever, skin rashes, generalized lymphadenopathy, hepatitis, and hepato-splenomegaly. Twenty-six patients with dapsone hypersensitivity syndrome were studied for clinical profile, outcome, and prognosis. The male:female ratio was 2.2:1, and the mean age was 33.19 years (range 13 to 64 years). The interval between start of dapsone therapy and appearance of symptoms varied from 2-7 weeks (mean 29.82 days). Twenty-four patients received dapsone as a part of multi-drug therapy for leprosy; the other two patients received dapsone for lichen planus and acne vulgaris. Exfoliative dermatitis was the most common cutaneous manifestation followed by erythematous maculo-papular eruption and Stevens-Johnson syndrome-like lesion. The other common systemic manifestations were: fever (26 cases), itching (22 cases), lymphadenopathy (21 cases), jaundice (21 cases), pallor (20 cases), hepatomegaly (19 cases), and pedal edema (14 cases). Investigation profile revealed elevated levels of serum liver enzymes in 100% of patients, elevated erythrocyte sedimentation rate in 92.3%, raised bilirubin in 84.6%, leucocytosis in 69.23%, low hemoglobin (<9 gm/dl) in 46.15% and hypoproteinemia in 42.3%. Eosinophilia, hemolytic anemia, and reticulocytosis count were found in 4 patients each. All the patients had favorable outcomes except three who died due to hepatic failure. Medical personnel must be aware of this potentially fatal syndrome, because it can cause considerable morbidity and mortality.
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PMID:Dapsone hypersensitivity syndrome: a clinico-epidemiological review. 1636 48

Chronic constipation that is unresponsive to laxative treatment is a severe illness, but children unresponsive to laxatives have been successfully treated with an elimination diet. We report the first cases of refractory chronic constipation caused by food hypersensitivity in adults. Four patients with refractory constipation who were unresponsive to high doses of laxatives were put on an oligo-antigenic diet and underwent successive double-blind, placebo-controlled, food challenges (DBPFC). Routine laboratory tests, immunological assays, colonoscopy, esophago-gastroduodenoscopy and rectal and duodenal histology were performed. While on an elimination diet, bowel habits normalized in all patients and a DBPFC challenge triggered the reappearance of constipation. In comparison with another 13 patients with refractory constipation unresponsive to the elimination diet, observed over the same period, the patients with food-hypersensitivity-related constipation had the following characteristics: longer duration of illness (p < 0.03), lower body mass index (p < 0.03), higher frequency of self-reported food intolerance (p < 0.01), higher frequency of nocturnal abdominal pain and anal itching (p < 0.01). In patients with food hypersensitivity, hemoglobin concentrations and peripheral leukocytes were lower than those in controls (p < 0.03). The duodenal and rectal mucosa histology showed lymphocyte and eosinophil infiltration, and the duodenal villi were flattened in two cases. In adult patients, refractory chronic constipation may be caused by food hypersensitivity and an elimination diet is effective in these subjects.
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PMID:Multiple food hypersensitivity as a cause of refractory chronic constipation in adults. 1663 22

A 21-year-old woman of Romany origin, in the third trimester of her fourth pregnancy, was admitted to the hospital because of a generalized erythematous and pustular eruption and desquamation involving her face, neck, trunk, and extremities. The skin changes were accompanied by fever (100.4 degrees F [38 degrees C]) and malaise. The patient was convinced that the dermatitis was induced by the consumption of "spoilt" pork sausage (bad smell, changed taste) approximately 24 hours earlier. Clinical examination revealed a woman with phototype III skin, black eyes, and black hair, in good general health. Widespread, symmetrical, moderately intense erythema and isolated or coalescing targetoid lesions studded with discrete, pinhead-sized, nonfollicular pustules in the center or at the periphery were distributed over her face, trunk, groins, and upper and lower extremities (Figures 1). On the neck and abdomen, lamellar desquamation was observed (Figure 2). Palms, soles, scalp, mucous membranes, hair, and nails were not affected. Nikolsky's sign was negative. The patient complained of very slight skin burning and itching. The pregnancy was proceeding without any complications and her obstetric status was normal. The woman had neither any accompanying diseases, nor previous personal or family history of psoriasis, nor any known allergies. She had taken no systemic medication (not even vitamins). She had three pregnancies; two ended with the delivery of healthy babies and one of them was aborted at her will. Laboratory studies revealed leukocytosis (13.2 x 109/L), neutrophilia (8 x 109/L), anemia (hemoglobin, 108 g/L), and an elevated erythrocyte sedimentation rate (68-110 mm/h). The results from the following investigations were normal: urinalysis, renal and hepatic function, serum albumin, Ca, Na, K, aspartate aminotransferase titer, cryoprotein, hepatitis B surface antigen, and serum markers for syphilis. Bacterial and fungal cultures of pustular content were sterile. A skin biopsy specimen of lesional skin revealed subcorneal pustules containing leukocytes and necrotic keratinocytes and a mixed perivascular inflammatory infiltrate with isolated eosinophils in the dermis (Figure 3). The patient was treated with systemic methylprednisolone in gradually reduced doses, fluocinonide cream 0.05%, and emollients. As a result, her fever disappeared and her erythema faded. Frequent obstetric examination and cardiotocography were normal and showed no evidence of placental insufficiency. At 40 weeks' gestation, the patient spontaneously gave birth without any complications to a healthy boy. She was discharged with complete resolution of the skin lesions, preceded by massive desquamation of the epidermis. The 1-year follow-up of the patient revealed no relapses or new pustular eruptions.
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PMID:Food-induced acute generalized exanthematous pustulosis in a pregnant woman. 1685 16

Few investigators have evaluated the usefulness of the JAK2 V617F mutation for explaining the phenotypic variations and for predicting the risk of major clinical events in primary myelofibrosis (PMF). In a transversal survey we assayed by allele-specific polymerase chain reaction (PCR) the JAK2 V617F mutational status in 304 patients with PMF. Multiple DNA samples were collected prospectively from 64 patients, and a highly sensitive quantitative PCR was used as a confirmatory test. In a longitudinal prospective study we determined the progression rate to clinically relevant outcomes in 174 patients who had JAK2 mutation determined at diagnosis. JAK2 V617F was identified in 63.4% of patients. None of the V617F-negative patients who were sequentially genotyped progressed to become V617F positive, whereas progression rate from heterozygous to homozygous mutation was 10 per 100 patient-years. JAK2 V617F mutation contributed to hemoglobin, aquagenic pruritus, and platelet count variability, whereas homozygous mutation was independently associated with higher white blood cell count, larger spleen size, and greater need for cytoreductive therapies. Adjusting for conventional risk factors, V617F mutation independently predicted the evolution toward large splenomegaly, need of splenectomy, and leukemic transformation. We conclude that JAK2 V617F genotype should be considered in any future risk stratification of patients with PMF.
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PMID:JAK2 V617F mutational status predicts progression to large splenomegaly and leukemic transformation in primary myelofibrosis. 1771 47

Pruritus is a common problem in dialysis patients. The aim of this study was to determine the cause(s) of pruritus and its relationship with inflammatory proteins. In a cross sectional study, all patients on hemodialysis at the Emam Khomaine and Sina Hospital, Tehran, Iran who did not have any pruritus-producing skin lesions were studied. They were questioned about the occurrence of pruritus during the preceding two weeks. Variables including inflammatory proteins (C-reactive protein, albumin, ferritin, transferrin, fibrinogen), hemoglobin, red blood cell indices, iron, iron binding capacity, transferring saturation, urea, creatinine, calcium, phosphorus, calcium x phosphorus product, alkaline phosphatase and parathormone were determined. Data were analyzed using Anova or Chi-square tests for evaluation of difference between variables. Of the 164 patients studied, 80 (49%) had pruritus. Of these, 45 subjects (23.8%) had severe and 35 (21.3%) mild to moderate pruritus. There were no significant differences between groups with or without pruritus for age, sex, duration on dialysis, dialysis adequacy, cause of renal failure and erythropoetin usage. Mean CRP was 16.6 mg/L; 58.5% of the patients had CRP > 10 mg/L. There was no significant correlation between CRP levels and presence or severity of pruritus. Also, none of the other inflammatory proteins revealed any significant differences. Among the other parameters, only the mean MCV levels were significantly different between the three groups (P < 0.05). Our study suggests that inflammatory proteins do not play any part in hemodialysis associated pruritus.
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PMID:Inflammation and pruritus in hemodialysis patients. 1808 25

This study was carried out on 30 dwarf bucks to determine the effects of cypermethrin (CY) on clinical, hemato-biochemical and histopathological parameters. Animals were divided randomly into five equal groups, and each group was dipped in 0%, 0.1%, 0.4%, 0.8% or 1.6% CY, on days 0 and 15. Animals were monitored for clinical signs. Blood and serum samples were collected on day 0 and then fortnightly till day 75. Severe clinical signs comprising itching, restlessness, salivation, skin scratching and head shaking appeared at high doses (0.8% and 1.6% CY). Erythrocyte counts, hemoglobin, hematocrit, total protein, globulin and fibrinogen decreased significantly while total leukocyte counts, alanine aminotransferase and aspartate aminotransferase concentration increased significantly in all the treated groups. In the liver, necrosis of hepatocytes along with cytoplasmic vacuolation and fibroblasts proliferation were observed at a high dose of CY (1.6%). Microscopically kidneys showed congestion of parenchyma and condensation of epithelial cells of tubules along with deposition of casts in tubules. Shrinkage of glomerular capillaries and increased urinary spaces were pronounced in the high-dose group. Lungs exhibited accumulation of fibrinous exudation, thickening of alveolar walls, collapse and broken alveoli in animals treated with a high dose of CY. It was concluded that CY caused dose-dependent effects on all parameters studied. High doses of CY (0.8% and 1.6% solution) affected the parameters on erythrocytes and leukocytes for whole evaluation period, while effects on plasma proteins were transient and on ALT, AST and fibrinogen were transient but lasted a few weeks longer.
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PMID:Effects of cypermethrin on some clinico-hemato-biochemical and pathological parameters in male dwarf goats (Capra hircus). 1877 26

Pruritus is one of the commonest symptoms of dermatologic appearances in uraemic syndrome and it occurs in 90% of patients on dialysis with different etiology and pathophysiology. The aim of the study was to estimate the frequency of uraemic pruritus and the comparison with clinical and biochemical parameters in 124 patients treated by chronic haemodialysis at Department of Haemodialysis, Clinical Centre in Kragujevac. The routine laboratory analyses were carried out in the examined patients and the concentration of parathyroid hormone was determined. The study was based on data from history of disease and questionnaire taken out in all patients. Of 124 patients 46.8% had symptoms of uraemic pruritus. Concentration of urea, albumin concentration, iron, parameters UIBC, as well as hyperglycemia and time on dialysis are the significant are significantly correlated with uraemic pruritus. 27.6% of the examined patients had itching of all the body. Between the patients with localized itching and patients with generalized itching, there are statistically significant differences in the following parameters: erythrocyte count, hemoglobin concentration, hematocrit and TIBC, as well as glycemia concentration.
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PMID:Parametres of clinical and biohumoral status of pruritus in patients on chronic haemodialysis. 1892 71

Intestinal parasitic infection prevalence in children who had been brought to our hospital together with related factors. The study was carried out in 400 children who were chosen at random among those brought to our hospital. All stool samples were examined with nativelugol, formol-ether, Kinyon acid-fast, methods. The cellophane tape preparations and hemoglobin concentration measurement were used. Intestinal parasites found in 156 of 400 (39%) children were Giardia intestinalis (19.8%) Enterobius vermicularis (15%), Blastocystis hominis (5.8%). Socio-economic and educational level of patient's family, living in urban area, having abdominal pain, anal itching, salivation during sleep, and nasal itching had been found related with the prevalence of parasitic infection. No relationship were found in the other factors. Because WHO guidelines favor routine screening and treatment of parasitic infections of school-age children when the prevalence of parasitic infections in community exceeds 50%, all children should be evaluated for parasitic infections if they have one or more risk factors.
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PMID:[The distribution of intestinal parasites and their causative factors in children]. 1915 10

Ferumoxytol is an intravenous iron preparation for treatment of the anemia of chronic kidney disease (CKD). It is a carbohydrate-coated, superparamagnetic iron oxide nanoparticle. Because little free iron is present in the preparation, doses of 510 mg have been administered safely in as little as 17 seconds. Two prospective, randomized studies compared two doses of ferumoxytol 510 mg given in 5 +/- 3 days with 3 weeks of oral iron 200 mg/day (as ferrous fumarate) in anemic patients with CKD. One study enrolled 304 patients with stages 1-5 CKD (predialysis), and the other study enrolled 230 patients with stage 5D CKD (undergoing hemodialysis). In both studies, a greater increase in hemoglobin level from baseline to end of study (day 35) was noted in patients who received ferumoxytol compared with those who received oral iron (mean +/- SD 0.82 +/- 1.24 vs 0.16 +/- 1.02 g/dl in patients with stages 1-5 CKD and 1.02 +/- 1.13 vs 0.46 +/- 1.06 g/dl in patients with stage 5D CKD, p<0.001). A greater proportion of both predialysis and hemodialysis patients who received ferumoxytol had hemoglobin level increases from baseline of 1 g/dl or more compared with those who received oral iron (p<0.001). In a prospective, double-blind, crossover study of more than 700 patients with CKD stages 1-5D that compared the safety of ferumoxytol with normal saline injection, the rates of treatment-related adverse events were 5.2% and 4.5%, respectively. Serious treatment-related adverse events were seen in one patient in each treatment group. The most common adverse events with ferumoxytol occurred at the injection site (bruising, pain, swelling, erythema). Dizziness, nausea, pruritus, headache, and fatigue occurred in less than 2% of patients receiving ferumoxytol, with a similar frequency noted after administration of normal saline. In short-term studies, intravenous ferumoxytol was safely and rapidly administered, and was more effective than oral iron therapy in increasing hemoglobin levels in anemic patients with CKD. Long-term clinical trials with clinical outcomes and studies comparing ferumoxytol with other parenteral iron agents will help define the role of ferumoxytol in treating the anemia of CKD.
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PMID:Ferumoxytol: a new intravenous iron preparation for the treatment of iron deficiency anemia in patients with chronic kidney disease. 2003 Apr 75

To evaluate the health impact of spraying organophosphorus insecticides (OPs), 34 male sprayers in the mango belt of Malihabad, a small town located 27 km from Lucknow in North India was selected. Plasma butyryl cholinesterase (PBChE) and complete blood count were assessed among sprayers after spraying pesticides and the findings obtained were compared with those determined in a reference group (n = 18). The most common symptoms observed were burning sensation in the eyes (8.82%), itching/skin irritation (23.52%) and chest symptoms (32.35%) in the exposed workers. Plasma butyrylcholinesterase (PBChE) was significantly decreased in workers. The results indicated significant decrease in the mean value of hemoglobin, hematocrit and platelets count; however, significantly higher count of leukocytes was also observed in the exposed group (sprayers) compared to that observed in the control group (P < 0.05). Monitoring of PBChE in pesticide sprayers could be useful to predict and prevent health hazards of OPs.
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PMID:Monitoring of plasma butyrylcholinesterase activity and hematological parameters in pesticide sprayers. 2004 Sep 95


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