Congenital methemoglobinemia due to methemoglobin reductase deficiency in two unrelated American black families.
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Biomedical subjects
Publications and source records attributed to E Hegesh.
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Reference values are presented for the activity of fructose-1-phosphate aldolase (F1PA) and fructose-1,6-bisphosphate aldolase (FBPA) in the small intestinal mucosa of 32 nonaffected children, 8 nonaffected adults and 2 children with hereditary fructose intolerance (HFI). The 96% confidence limits for F1PA in children are 1.55 to 43.0 u/g protein, completely distinct from the results of the two affected children (1.3 and less than 0.1 u/g protein). With fructose-1,6-bisphosphate as subtrate, the 96% confidence limits are 10 to 324 u/g protein and the values for the two affected children, 23.7 and 9.3 u/g. Among the nonaffected children two mucosal biopsies with F1PA activities less than 1.55 u/g were found. In one mucosal biopsy among the nonaffected children an FBPA activity less than 10 u/g was recorded. The data are interpreted as indicating that the determination of F1PA activity in intestinal mucosa is a highly sensitive test in detecting individuals with HFI. However, the specifity of the test is not absolute. Diagnosis should be based on both clinical and laboratory considerations. The determination of FBPA activity in the same biopsy specimen does not contribute substantially to the differential diagnosis.
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A case of congenital enzymopenic methemoglobinemia associated with severe mental retardation is described. The deficiency of cytochrome b5 reductase activity in the erythrocytes and the leukocytes of the propositus is demonstrated by kinetic measurement and by disc gel electrophoresis. Analysis of cultured amniotic fluid cells during a second pregnancy of the mother revealed an almost complete deficiency of the enzyme. The absence of cytochrome b5 reductase activity in the blood from the aborted fetus confirmed the prenatal diagnosis. The data presented support the opinion that in pregnancies at risk for the severe form of congenital enzymopenic methemoglobinemia, prenatal diagnosis is warranted.
Alkaline phosphatase (AP) activity is an accepted marker of epithelial cell differentiation and integrity in intestinal mucosal explant systems. In experiments involving AP it is usually expressed as activity per unit protein in tissue culture. It has been previously demonstrated that during organ culture a considerable amount of protein and nucleic acid (NA) may leave the cell and enter the surrounding medium. It may therefore not be appropriate to measure enzyme synthesis in relation to total tissue protein. In this study we attempted to gather additional information on enzyme dynamics and tissue integrity during organ culture of intestinal mucosal explants from children with celiac disease (CD) on a normal diet (ND) (n = 21), children with CD on a gluten-free diet (GFD) (n = 12), and patients with gastrointestinal disorders other than CD (controls) (n = 17). We confirmed the leakage of protein, NA, and AP from the tissue explant into the medium, and normalized the AP data by expressing AP as total AP in tissue plus medium per total NA in tissue plus medium. In patients with CD on a ND, the AP level at time 0 was 9.58 (+/- 12.2) mIU/micrograms NA and after 24 h culture rose to 21.9 (+/- 15.7) mIU/micrograms NA. In patients with CD on a GFD the baseline AP level was 24.9 (+/- 34.8) mIU/micrograms NA, and this value rose after culture to 28.6 (+/- 17.9) mIU/micrograms NA. In the controls the initial AP activity was 17.2 (+/- 15.7) mIU/micrograms NA, and the increase was to 38 (+/- 27.6) mIU/micrograms NA.(ABSTRACT TRUNCATED AT 250 WORDS)
A sensitive, precise enzymic/spectrophotometric method for determining cytochrome b5 in small amounts of blood is described. Mean values for healthy individuals, ages 20 to 70 years, were 0.26 (SD 0.03) mumol per liter of erythrocytes or 0.87 (SD 0.14) nmol per gram of hemoglobin. We believe the assay is preferable to methods described hitherto, primarily because of its high sensitivity.
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Infantile methemoglobinemia is of much more frequent occurrence among hospitalized newborns and young infants than is generally appreciated. When present, acute diarrhoea of different etiologies is almost exclusively the cause of hospitalization. No correlation between this condition and ingestion of food or water containing high concentrations of nitrates or nitrites was found. This study demonstrates for the first time that high blood nitrates are a regular part of the syndrome. The evidence presented is interpreted as indicating that diarrhoea results in endogenous, de novo synthesis of nitrites, and this is the principal cause of infantile methemoglobinemia.
Of the various common assayed parameters of iron metabolism, serum ferritin levels are the most discriminatory in distinguishing between non-treated celiac disease and other gastrointestinal disorders in the pediatric age group. Patients on normal diets usually have very low ferritin levels that increase at an average rate of 1 microgram/1/month when placed on a gluten-free diet. When the patient returns to a normal diet, however, ferritin levels decrease rapidly at an average rate of about 4 microgram/1/month. There is a relationship between abnormal intestinal changes and low ferritin levels in celiac disease with improvement in both when the patient is on a gluten-free diet. It is suggested that serial blood ferritin evaluations together with the leukocyte migration inhibition factor production assay should eliminate the need for invasive intestinal biopsies for the confirmation and possible follow-up to response to treatment.
Rheometric properties of cervical mucus were studied with the Ovutimer in 26 women. 14 women had regular menstrual cycles, 12 had menstrual irregularities and received treatment to induce ovulation. In 21 women (80.7%) a significant correlation was found between the ovulation time as established by the luteinizing hormone surge, and ovulation time as established by the Ovutimer test. The instrument was found satisfactorily accurate in establishing the day of ovulation in almost all cases.
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