Hypervitaminosis A Inducing Intra-hepatic Cholestasis—A Rare Case Report

The use of over-the-counter supplements is commonplace in today's health conscious society. We present an unusual case of intrahepatic cholestasis caused by vitamin A intoxication. The patient consumed one Herbalife^TM shake with two multivitamin tablets of the same brand for 12 years. When calculated this equated to more than the recommended daily allowance for vitamin A consumption. Deranged liver function tests were consistent with a cholestatic process. Liver biopsy was obtained and revealed features pathognomonic of vitamin A toxicity, without the usual fibrosis. When the supplements were ceased, his jaundice and alkaline phosphatase completely normalized. This case highlights the importance of health care providers documenting non-prescribed dietary supplements and considering them in the etiology of cholestatic liver disease.     

Ultrastructural Changes in Livers of Two Patients with Hypervitaminosis A

The principal distinctive ultrastructural changes observed in the livers of 2 patients with chronic hypervitaminosis A were perisinusoidal fibrosis and massive accumulation of lipid-storing cells (Ito cells). The fibrosis consisted of a network of basement membranes with numerous bundles of collagen and reticulum fibrils. This network contained numerous Ito cells, and moderate numbers of lymphocytes, macrophoges and other mesenchymal cells. Impairment of blood flow by perisinusoidal fibrosis probably resulted in the secondary alterations in hepatocytes which included cellular atrophy and formation of cytoplasmic bullae.     

Hypervitaminosis D associated with drinking milk.

BACKGROUND. Vitamin D has been added to milk in the United States since the 1930s to prevent rickets. We report the unusual occurrence of eight cases of vitamin D intoxication that appear to have been caused by excessive vitamin D fortification of dairy milk. METHODS. Medical records were reviewed and a dietary questionnaire was sent to eight patients who had unexplained hypervitaminosis D. Vitamin D analyses with high-performance liquid chromatography were performed on samples of the patients' serum, the dairy milk they drank, and the vitamin D concentrate added to the milk. RESULTS. All eight patients drank milk produced by a local dairy in amounts ranging from 1/2 to 3 cups (118 to 710 ml) daily. All had elevated serum 25-hydroxyvitamin D concentrations (mean [+/- SD], 731 +/- 434 nmol per liter [293 +/- 174 ng per milliliter]). Six of the eight patients had elevated serum vitamin D3 concentrations. Of the eight patients, seven had hypercalcemia and one had hypercalciuria but normocalcemia (mean serum calcium, 3.14 +/- 0.51 mmol per liter [12.6 +/- 2.1 mg per deciliter]). Analysis of the dairy's vitamin D-fortified milk revealed concentrations of vitamin D3 (cholecalciferol) that ranged from undetectable to as high as 232,565 IU per quart (245,840 IU per liter). An analysis of the concentrate that was used to fortify the milk, labeled as containing vitamin D2 (ergocalciferol), revealed that it contained vitamin D3. CONCLUSIONS. Hypervitaminosis D may result from drinking milk that is incorrectly and excessively fortified with vitamin D. Milk that is fortified with vitamin D must be carefully monitored.     

A re-examination of mitotic activity in the early chick embryo

Summary As a result of extensive mitotic index analysis in colchicine-arrested chick embryos during gastrulation, it was ascertained that the primitive streak is a region of elevated mitotic index as compared to the surrounding tissue. Along the cephalo-caudal axis, the embryo displays two large peaks of mitotic index, one at the posterior end of the primitive streak and the other just anterior to Hensen's node. The length of the various phases of the mitotic period was determined in vitro by time-lapse filming, and the colchicine-arrested mitotic indices in vivo and in vitro were determined and compared for various regions. Some observations regarding the orientation of mitotic spindles and abnormal mitosis in vitro are also included, and the relevance of the above observations to early embryonic development is discussed.     

A histochemical study of epithelial mucin in the chick chorioallantois

Histochemical methods demonstrate the accumulation of two types of mucous inclusion in the allantoic epithelial cells of the chick embryo. One type of inclusion contains a sialomucin that is PAS-reactive, unstained by Alcian blue and other anionophilic dyes and is susceptible to digestion by Vibrio cholerae neuraminidase. The second inclusion contains an apparent sulfomucin which is Alcianophilic at pH 1.0, unstained by anionophilic dyes after a methylation-demethylation sequence and resistant to testicular hyaluronidase. This sulfomucin exhibits PAS reactivity after desulfation procedures. Both types of mucus occur in individual cells and are normal components of the chorioallantois. Accumulation of the inclusions is enhanced by lowering the pH of the allantoic fluid or as a result of organ transplantation.     

Endothelial heterogeneity in the chick wing bud: A morphometric study

Summary The microvascular endothelium of the chick wing bud at stages 22, 27, and 32 was evaluated by ultrastructural morphometry. The rationale for this study is based on the hypothesis that endothelial cells exhibit variation in structure and function during cytodifferentiation. The microvessels had a luminal diameter range such that they were classified as capillaries. The thin continuous endothelium was devoid of a basal lamina. The endothelium had a very small number of plasmalemmal vesicles; vacuoles were however present for all stages and in some cases were abundant. The temporal findings were that endothelial cell thickness increases, plasmalemmal vesicle densities decrease, and the densities of cytoplasmic vacuoles increase. The spatial results were that endothelial cells in proximal regions of the limb have a greater thickness, contain fewer vesicles and have more vacuoles than those in distal regions. In general, these results indicate that endothelial ultrastructural heterogeneity occurs within a 31/2 day timespan of wing bud development. The discussion considers the results with regard to recent reports on endothelial cell heterogeneity.     

A reexamination of the role of microfilaments in neurulation in the chick embryo

Formation of wedge-shaped neuroepithelial cells, owing to the constriction of apical bands of microfilaments, is widely believed to play a major part in bending of the neural plate. Although cell "wedging" occurs during neurulation, its exact role in bending is unknown. Likewise, although microfilament bands occupy the apices of neuroepithelial cells, whether these structures are required for cell wedging is unknown. Finally, although it is known that cytochalasins interfere with neurulation, it is unknown whether they block shaping or furrowing of the neural plate, or elevation, convergence, or fusion of the neural folds. The purpose of this study was to reexamine the role of microfilaments in neurulation in the chick embryo. Embryos were treated with cytochalasin D (CD) to depolymerize microfilaments and were analyzed 4-24 hr later. CD did not prevent neural plate shaping, median neural plate furrowing, wedging of median neuroepithelial cells, or neural fold elevation. However, dorsolateral neural plate furrowing, wedging of dorsolateral neuroepithelial cells, and convergence of the neural folds were blocked frequently by CD. In addition, neural folds always failed to fuse across the midline in embryos treated with CD, and neural crest cell migration was prevented. These data indicate that only the later aspects of neurulation may require microfilaments, and that certain neuroepithelial cells, particularly those that normally wedge with median furrowing and elevation of the neural folds, become (and remain) wedge-shaped in the absence of apical microfilament bands. Thus, microfilament-mediated constriction of neuroepithelial cell apices is not the major force for median neuroepithelial cell wedging and elevation of the chick neural plate. Further studies are needed to localize the motor(s) for these processes.     

Hypervitaminosis B12 in maintenance hemodialysis patients receiving massive supplementation of vitamin B12

We have administered routinely a multivitamin preparation containing a megadose of B12 to 106 hemodialysis patients after dialysis treatments. We found that these patients had very high levels of serum vitamin B12 which returned to original values only after a period of three years after stopping the vitamin. Discontinuing therapy had no effect on hemoglobin, mean erythrocyte corpuscular volume, or motor nerve conduction velocity. It is not known whether maintaining a prolonged high level of vitamin B12 is harmful. However, animal and epidemiologic studies have suggested that both cobalamin and cobalt may be potentially toxic. In view of the absence of demonstrable benefit and the possible risk of toxicity, we believe that the use of such megadose vitamin compounds in dialysis patients should be re-evaluated.