Biomedical subjects
Publications and source records attributed to T D Allen.
Vesicostomy was done as a means of temporary urinary diversion in 16 children less than 3 years old. Adequate urinary drainage was not present in these children yet definitive corrective measures were not considered advisable. The good results achieved sugges that this operation is ideally suited for this purpose.
The patient whose genitalia are ambiguous or are inappropriate for the assigned sex presents the physician with a set of problems requiring a thorough grasp of sexual differentiation, development and function. Although several reviews have covered various aspects of these matters, these texts do not cover recent advances in understanding normal and abnormal sexual development nor do they provide an integrated guide to the management of intersex cases. Our objectives are to show the clinical relevance of recent advances in understanding the determinants of normal and abnormal sexual differentiation, to indicate the improved diagnostic procedures now available and to provide specific guidelines for optimal case management in the light of current medical knowledge and psychological and ethical understanding.
The relationship between ageing and transformation has been investigated by a serial study of the changes in cell-surface morphology as normal and carcinogen-treated cells progressed in culture. A progressive increase in the density of cell surface microvilli occurred in association with the adoption of a more rounded profile and concomitant increase in the rate of cell detachment. These changes occurred earlier after carcinogen treatment, which appeared to indicate a carcinogen-induced acceleration of ageing. The alterations have also been described as characteristic of the transformed state. The observations suggest that the expression of in vitro transformation may be the result of continuous selection from a population with genetic instability and variable morphology.
Three dimensional gels of native type I collagen fibres have been used as a substratum for the growth and migration of Chinese hamster ovary cells (fibroblastoid cell line) and RPMI-3460 melanoma cells (tumorigenic cell line from Syrian hamster). Quantitative data concerning the migration of these cells from the gel surface into the 3-dimensional collagen gel matrix have been obtained. The migration of both cell types into the collagen gel matrix is not accompanied by the degradation of collagen fibres. The possible implications of these observations for tumour cell invasion in vivo are discussed.
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In children without an organic disorder, bladder retraining, not surgery or medication, can be the key to successful treatment of dysfunctional voiding.
When freshly isolated rabbit marrow cells were cultured either in vitro or in diffusion chambers in vivo, the hemopoietic cells disappeared and there was a proliferation of the stromal cell population. The colonies formed in vitro were mainly fibroblastic, and this cell type predominated in confluent cultures. Staining for alkaline phosphatase activity and for the Von Kossa reaction was negative in in vitro cultures. However, marrow cell suspensions or fibroblasts harvested from in vitro culture of marrow cells, gave rise to a mixture of bone, cartilage and fibrous tissue in diffusion chambers implanted into the peritoneal cavity. In contrast, only a soft fibrous tissue developed from spleen fibroblasts in diffusion chambers. Differentiation of osteogenic tissue within diffusion chambers fell into two categories: (1) Formation of bone in a fibrous layer surrounding cartilage; (2) intramembranous bone formed directly within fibrous tissue unassociated with cartilage. In both cases alkaline phosphatase activity appeared before the onset of mineralization, and decreased as the first signs of mineral became apparent. The present results suggest that postnatal marrow contains osteogenic precursors with the potential to differentiate via either of the two major paths followed during skeletal development in the embryo. Clonal analysis of the marrow stromal cell population will be required to clarify whether osteo-, chondro-, and fibrogenic cells are the products of one stromal cell line modulated by the microenvironment, or whether there are distinct cell lines for each type.
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Cultured hepatocellular carcinoma cells were studied during anchorage-independent growth in semi solid medium (Methocel). The regular occurrence of mitotic figures both at the surface and within the colonies precludes the possibility of such colonies being formed by re-aggregation. The estimated population doubling time in the three-dimensional (3-D) colonies is consistent with those two-dimensional of (2-D) colonies. Structures resembling bile canaliculi were observed between the closely opposed membranes from the well packed adjacent cells. Cell surface and ultrastructural features of the colonies and individual cells are presented and comparisons made with 2-D growth of normal and malignant liver cells in vitro. The formation of 3-D colonies may not only be an assay for transformed cells but also for predicting the type of tumors produced by re-innoculation of the in vitro transformed cells.
The growth potential of normal and transformed rat liver epithelial cells in culture was investigated under various experimental conditions. The control cells failed to form colonies over a base layer of living parent cells, whereas transformed cells formed distinct colonies. Contact with living normal liver cells is required for the growth inhibition of the untransformed cells. Malignant cells capable of producing hepatocellular carcinomas in vivo exhibited signs of invasion in vitro. Altered properties of hepatic cells during the early stages of transformation can be assessed by plating such cell population over a living base layer of normal liver cells.
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Maintenance of myelopoiesis and pluripotential stem cell production for prolonged periods in vitro hitherto has been limited to mouse bone marrow culture. In an effort to adapt the system for use in higher species, particularly in human and non-human primates, studies were undertaken using the prosimian species, Tupaia glis (tree shrew). In a number of experiments the duration of sustained normal hematopoiesis observed in cultures of this species, following a single inoculum of 5 X 10(6)--10(7) bone marrow cells, with or without addition of fresh allogeneic bone marrow exceeded 1 yr. Analysis of suspension cells obtained by weekly demidepopulation of such cultures revealed production of CFU-C, differentiating neutrophils, and basophils at high levels. Direct comparison with murine cultures indicated that in both species a complex series of cellular interactions takes place within an adherent environment of marrow-derived endothelial cells, macrophages, and fat-containing cells. Certain functional and ultrastructural features served to distinguish murine from Tupaia marrow cultures, and the prolonged duration of in vitro hematopoiesis in the latter species could be attributed to a regenerative capacity possessed by its adherent hematopoietic microenvironment. The availability of this primate marrow culture system should facilitate studies of hematopoiesis, viral leukemogenesis, and transplantation biology, which have more direct relevance to man than that provided by the existing murine system.
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Eight patients with congenital microphallus were investigated. Plasma luteinizing hormone, follicle-stimulating hormone, testosterone and androstenedione levels were obtained in all cases. In addition, the response to the administration of human chorionic gonadotropin, luteinizing horomone-releasing hormone and adrenocorticotropic hormone, the assessment of testicular histology by electron microscopy and the measurement of dihydrotestosterone formation by preputial skin were determined in some patients. The results of these studies were compared to similar studies in 6 normal prepubertal boys, 4 boys with bilateral cryptorchidism, 1 male infant with anorchia and 1 adult with hypogonadotropic hypogonadism. The clinical and endocrinological findings in the 8 patients with microphallus can be divided into 2 distinct categories. In 5 patients the disorder is familial, gonadotropin levels are low and there is a normal response to stimulation with chorionic gonadotropin. The data are compatible with the possibility that 3 (possibly 5) of the 8 patients with microphallus have hypogonadotropic hypogonadism. In the other group the cases are sporadic, serum luteinizing hormone and follicle-stimulating hormone levels are elevated and plasma testosterone failed to increase after short-term treatment with chorionic gonadotropin. In these patients a primary testicular disorder appears to be responsible. Experimental and clinical evidence suggests that microphallus results from defective testicular function during the second and third trimesters of pregnancy, either as the result of defective gonadotropin secretion or defective androgen synthesis.
Simultaneous measurements of the intravesical pressure, electromyographic activity of the anal sphincter and the urinary flow rate in 17 children with dysfunctional voiding problems have shown a variety of unusual patterns, each distinct for the particular child but all with the common denominator of failure to coordinate detrusor and sphincter activity. We postulate that these patterns represent persistence of the transitional phase in the development of micturitional control whereby the child learns to prevent involuntary wetting by forceful contraction of the external urethral sphincter.
The clinical and endocrinological features of 15 male subjects with small but normally formed external genitalia are reviewed. Nine of these patients had a simple microphallus alone, while the other 6 patients exhibited associated central nervous system defects. The endocrine data obtained from both groups were the same and were consistent with defective hypothalamic function. Parenteral testosterone seems to be the present treatment of choice but we believe it should be started early in life to take advantage of the greater hyperplastic response of the young.