Juvenile channel catfish, Ictalurus punctatus, were fed semipurified basal diets containing 0, 0.2, 0.5, 1.0, 4.0 or 10.0 mg/kg of folic acid or 10 g/kg of succinylsulfathiazole in aquaria for 15 wk. Fish fed the sulfonamide showed higher mortality, lower weight gain, lower thrombocyte counts, higher hemocytoblast and neutrophil counts, and lower liver folate concentrations than did control fish (0 folic acid), indicating that significant intestinal bacterial synthesis of folate occurs in channel catfish. There were positive quadratic regressions of weight gain, hematocrit, erythrocyte and leukocyte numbers, and positive linear regressions of plasma and liver folate on dietary folic acid concentrations. Broken-line analysis showed that the dietary requirements for folic acid for optimum weight gain, hematocrit, and erythrocyte and leukocyte numbers were 1.01, 1.17, 1.12 and 1.15 mg/kg, respectively. Plasma and liver concentrations of folate associated with normal growth and hematopoiesis were 22.9 nmol/L and 20.0 nmol/g, respectively. Ratios of leukocytes and lymphocytes to erythrocytes were maximal in fish fed 4.0 mg folic acid/kg, indicating that immunocompetence may increase as the dietary dose exceeds that required for normal growth. Anemia in folate-deficient channel catfish was characterized by pale livers, spleens, gills and kidneys, and by poikilocytosis, anisocytosis, pyknosis, cytoplasmic clearing, increased numbers of hemocytoblasts, macrocytosis, and binucleated erythrocytes or ''spectacle'' cells.
Tetrahydrobiopterin is essential for brain cells to make monoamine neurotransmitters. It has been reported that the concentrations of tetrahydrobiopterin in plasma and urine are low in certain mental disorders and that oral supplements are beneficial. A group of Japanese investigators have been conducting clinical trials of the effect of administration of tetrahydrobiopterin to autistic children and reported that it is beneficial with no significant side effects. We, therefore, initiated a study to assess plasma and urinary levels of tetrahydrobiopterin in infantile autism to see if they are reduced. Besides tetrahydrobiopterin, we also determined plasma and urinary levels of neopterin and monapterin in these individuals in order to evaluate the status of dihydroneopterin triphosphate, a key biosynthetic precursor of tetrahydrobiopterin. Sixteen autistic children and 12 healthy controls were included in this study. Results indicated that the plasma and urinary levels of tetrahydrobiopterin are not statistically different between the two groups and, therefore, no simple explanation for the beneficial effects of administration of tetrahydrobiopterin on autistic children can be offered at the present time. In contrast, plasma and urinary levels of neopterin were depressed (.01<p<.05) and plasma monapterin was also significantly depressed (p<.01) in autistic subjects compared with controls. Levels of other pterins, including folate, were not statistically different between the two groups. The basis for this depression in neopterin and monapterin is unknown. It does not seem likely that this depression could be attributed to a difference in age or T-lymphocyte/macrophage activity. However, further studies are needed to investigate these possibilities.
A study was undertaken to evaluate the utility of human papillomavirus (HPV) DNA screening and colposcopy in the management of women whose Papanicolaou smears demonstrated atypia less than dysplasia. Fifty patients whose initial Papanicolaou smears were interpreted as showing atypia less than dysplasia were evaluated for the presence of HPV 16 DNA in exfoliated cervicovaginal cells and for histologic findings on biopsy. Those 50 patients were compared to two groups of patients: one consisting of 124 patients with biopsy-documented cervical intraepithelial neoplasia (CIN) and another of 112 patients with normal Papanicolaou smears. The presence of HPV 16 DNA was confirmed with Southern analysis in 46% of patients with atypical Papanicolaou smears, 46% with confirmed CIN and 11.6% with normal Papanicolaou smears. The 50 patients with atypical smears underwent colposcopically directed cervical biopsies, revealing the following results: 14 (28%) had normal histology, 29 (58%) had koilocytosis without dysplasia, and 7 (14%) had CIN. HPV 16 DNA was present in exfoliated cervicovaginal cells from a large percentage of patients from each category (50%) of patients with normal histology, 41.2% with koilocytosis and 57% with CIN). HPV 16 DNA screening did not predict which patients with atypical smears had underlying CIN. Colposcopically directed biopsy remains the evaluation method of choice.