Metabolic N-oxygenation of 2,4-diamino-6-substituted pyrimidines

Biological oxidation of 2,4-diamino-6-substituted pyrimidines have been studied using hepatic microsomes from various mammalian species. The nature of the enzyme(s) involved in the oxidation has been elucidated using various enzyme inhibitors and inducing agents. The 3-N-oxides were formed with 6-piperidino-, 6-diethylamino-, 6-methyl-, and 6-chloro-substituted 2,4-diaminopyrimidines: no evidence of 1-N-oxide formation was obtained. With the 6-hydroxy-, 6-amino-, and unsubstituted 2,4-diaminopyrimidines and melamine, no N-oxidative metabolite was detected. The differences in N-oxide formation was discussed in terms of the effect of substituents on tautomerism and electron distribution. The N-oxygenation was mediated via a cytochrome P450 dependent system.     

Comparison of PET, MRI, and CT with pathology in a proven case of Alzheimer's disease

Positron emission tomography (PET) with fluorodeoxyglucose (FDG), magnetic resonance imaging (MRI), and CT were carried out in a patient with Alzheimer's disease 16 months before he died. At autopsy, the gross appearance of the brain correlated with MRI and CT, which showed some regional atrophy. These were much less revealing than PET, which correlated with microscopic findings of neuronal loss and proliferation of glia. In areas of moderately impaired local cerebral metabolic rate of glucose, as revealed by reduced FDG uptake, there was some gliosis, primarily around the numerous senile plaques. In areas of severe metabolic impairment, there was a profound loss of neurons, extensive gliosis, and a diminished appearance of plaques. PET-FDG is a better measure of the severity of Alzheimer's disease than MRI or CT, because it reflects the degree of neuronal pathology.     

Neutropenic enterocolitis in adults with acute leukemia

Neutropenic enterocolitis has been previously described only by case reports and literature reviews. Of 499 adults with acute leukemia seen over a 23-year period (1962 to 1985), 13 cases (2.6%) of neutropenic enterocolitis have been reported. Eleven of these 13 patients were profoundly neutropenic (mean white blood cell count, 472/cu mm) and developed abdominal symptoms during either initial induction or relapse of acute leukemia. Histologic confirmation was available in ten cases, five cases after surgical resection and five cases at autopsy after nonoperative management. Three patients with isolated ileocecal inflammation without infarction at the time of surgery were successfully managed without resection. Five patients treated with surgery died four to 64 weeks postoperatively (mean survival, 21.6 weeks) of nonsurgical complications of leukemia. Three patients were still alive, one patient 42 months after right hemicolectomy and two patients five months after exploration only. All five patients managed medically died an average of 1.4 days (range, zero to four days) after the onset of abdominal pain. Survival in patients with acute leukemia who develop neutropenic enterocolitis is determined by early recognition and appropriate surgical exploration that can be expected to yield an acceptable operative mortality.     

Efficacy of phototherapy in non-haemolytic hyperbilirubinaemia

Clinical experience of phototherapy for non-haemolytic hyperbilirubinaemia in 3999 infants in Kandang Kerbau Hospital, Singapore, is documented. Phototherapy was most effective in extremely preterm infants with very low birth weight (gestation less than or equal to 32 weeks, birth weight less than or equal to 1500 g) and least effective in full term infants with very low birth weight (gestation greater than or equal to 37 weeks, birth weight less than or equal to 1500 g) and large preterm infants (gestation less than 37 weeks, birth weight greater than 2270 g). Overall, phototherapy was effective in almost all the infants, with a failure rate of only 2.00/1000 infants. No characteristic features common to all the failures could be detected. The bilirubin rebound was usually mild; repeat phototherapy was required in only 30 infants (7.50/1000), with the response to the second exposure comparable to that to the first. No infant required a third exposure. All the infants tolerated phototherapy well, none developing any illness that could be attributed to the treatment. This clinical experience shows that phototherapy for the treatment of nonhaemolytic hyperbilirubinaemia is effective and safe.     

Multiple regression analysis of twin data obtained from selected samples

The multiple regression analysis of twin data in which a cotwin's score is predicted from that of a proband (the member of a twin pair selected because of a deviant score) and the coefficient of relationship provides a powerful test of genetic etiology (DeFries and Fulker: Behav Genet 15:467-473, 1985). Moreover, when an augmented model containing an interaction term is fitted to the same data set, direct estimates of heritability (h2) and the proportion of variance owing to shared environmental influences (c2) are also obtained. In the present paper, the expected partial regression coefficients estimated from these models are derived, and the flexibility of the general approach is illustrated. An extended model is formulated for the analysis of data from combined samples of affected and control twin pairs that yields tests for differential h2 and c2 in the two groups as well as pooled estimates of these parameters. The application of these models is illustrated by an analysis of data from reading-disabled and control twin pairs. Because of the ease, flexibility, and utility of the multiple regression analysis of twin data, it is an appealing alternative to more traditional model-fitting approaches.     

Regulation of in vivo IgE biosynthesis in mice with complete Freund's adjuvant

Complete Freund's adjuvant (CFA) administered before sensitization dampened the normal and cyclophosphamide-enhanced response of high and moderate IgE responder phenotype mice (CAF1 and C57B1/6J, respectively). CFA-induced suppression of IgE biosynthesis was effective in reducing anaphylactic histamine release from approximately 2,900 ng histamine per milliliter to background levels (less than 100 ng/ml). CFA-induced ascites fluid was able to reduce the cyclophosphamide-enhanced IgE response of low-responder phenotype SJL mice from 1:320 to less than 1:5 as determined by passive cutaneous anaphylaxis. Muramyl dipeptide, a mycobacterial cell wall component capable of eliciting effects similar to those seen with CFA, was shown to induce suppression of IgE production if incorporated in incomplete Freund's adjuvant. Muramyl dipeptide administered in saline was ineffective, while incomplete Freund's adjuvant alone had some immunoregulatory properties. Ongoing IgE responses were less susceptible to regulation. CFA administered to sensitized C57B1/6J mice was ineffective in inducing IgE suppression when animals were challenged with antigen.     

Organic affective syndrome associated with metoclopramide: case report

Metoclopramide, a substituted benzamide derivative, was orally administered to a patient with intractable hiccups. Dysphoria, akathisia, depressed mood with suicidal ideation, insomnia, racing thoughts, and labile affect were seen following the administration of metoclopramide. The episode met criteria for an organic affective syndrome. It is suggested that the mental status of patients undergoing metoclopramide therapy be monitored, since these symptoms have not been previously reported.