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Biomedical subjects

D C Savage

Publications and source records attributed to D C Savage.

At least 91 records · Page 5Linked to original sources

Glycosylated haemoglobin levels in children with diabetes mellitus.

Total glycosylated haemoglobin (HbA1) levels were measured in 94 diabetic children aged between 3 and 19 years. The results were compared with traditional methods of assessing blood glucose control. HbA1 levels correlated with home urine glucose testing (P less than 0.05), with 24-hour urine glucose excretion (P less than 0.01), and with height velocity (P less than 0.001). Within the first two of these parameters there was a wide scatter of results, suggesting the inaccuracy of these methods for assessing control. The association of raised HbA1 levels with height velocities less than 10th centile shows the effect of poor control on growth. HbA1 may prove to be an objective method for assessing long-term blood glucose levels in diabetes, and thus it may be possible to determine the effect of good control in the prevention of the various diabetic complications.

Adolescent↗

Deficient 3 beta-hydroxy-5-ene steroid secretion by newborn infants.

Congenital adrenal hypoplasia is reported in two siblings. The first died at 16 months of purulent bronchopneumonia after a history of adrenal insufficiency. No gross adrenal tissue was found at autopsy and urinary steroids were not excreted in detectable amounts before death. In a subsequent uncomplicated pregnancy, extremely low estrogens were recorded in the last trimester. Analysis of steroids in the urine of the neontate by gas chromatography revealed virtual absence of 3 beta-hydroxy-5-ene steroids. These suggest hypoplasia of the fetal adrenal cortex. Metabolites of cortisol were excreted in normal amounts and responded adequately to ACTH stimulation. Neonatal hyponatremia was associated with subnormal excretion of corticosterone and aldosterone metabolites. It is proposed that in the perinatal period, the fetal zone is required for mineralocorticoid synthesis, possibly by providing essential precursor steroids, e.g. 21-hydroxypregnenolone.

Adrenal Insufficiency↗

Factors involved in colonization of the gut epithelial surface.

Some indigenous microbes form climax communities on gastrointestinal epithelial surfaces during succession in animals of many types. Most communities form in mucous layers on the surfaces, where some microbes in the communities may utilize the mucin as a source of carbon and energy. The mucous gel may also serve physically to stabilize the community. Some microbial types that colonize early during succession may serve, perhaps synergistically with dietary components, to lower the oxygen tension and oxidation-reduction potential so that oxygen-intolerant anaerobes can colonize the epithelial surfaces. Microbes in the communities may adhere to the epithelial surface; the mechanisms by which they adhere may depend upon a variety of factors, including the type of epithelium and the rate of flow of lumenal contents in the areas. Dietary fiber may influence the composition of these communities by providing nutrients for the microbes or altering their environmental conditions including peristaltic rate, mucous concentration and composition, and oxygen tension and oxidation-reduction potential.

Animals↗

Freeze-fracture study of the filamentous, segmented microorganism attached to the murine small bowel.

A freeze-fracture study has provided new information about the filamentous, segmented microorganism known to live in the murine small bowel. The intracellular bodies produced by this microbe appear to arise by a modified sporogenesis so that they are enclosed in an envelopment membrane at least prior to release by the filament mother cell. At least some of the intracellular bodies divide while still within the mother cell, suggesting a reproductive role for these structures. The host epithelial membrane remains intact at the site of attachment, but does appear to have a reduced concentration of intramembrane particles. Changes in the host cytoplasm adjacent to the attachment site are documented and interpreted to be a sol-gel transformation which may stabilize the attachment socket.

Animals↗

Growth and hormonal status of children treated for acute lymphoblastic leukaemia.

Growth and hypothalamic-pituitary function have been studied in children in long-term remission from acute lymphoblastic leukaemia (ALL). All 14 children are growing and developing normally; in the 8 children in whom the hypothalamic pituitary axis was investigated endocrine function is normal. Continuing long-term review of these children is essential, but hypothalamic-pituitary investigation is required only when there is a decrease in growth velocity or delay in the onset of puberty.

Adolescent↗

Combined test of anterior pituitary function in children.

A combined test of anterior pituitary function was used on 21 normal children. It shows that a comprehensive evaluation can be made of growth hormone, thyroid stimulating hormone, adrenocorticotrophic hormone, and gonadotrophin reserve. Simultaneous assessment of those peripheral glands associated with the anterior pituitary is possible by the measurement of thyroid hormones, cortisol, and gonadal steroids. The procedure can be completed in 4 hours with minimum inconvenience and distress to the child.

Child↗

Lactobacilli isolated from the stomach of conventional mice.

Twenty strains of lactobacilli isolated from the stomach of conventional mice were tested for their ability to ferment or hydrolyze substrates that may be present in the stomach habitat. The lactobacilli could be placed in four groups (A to D) depending on their ability to ferment N-acetylglucosamine, dextrin, cellobiose, gum arabic, and xylan. The majority of the isolates belonged to groups A and D. Group A strains did not resemble previously described Lactobacillus species, but group D strains were identified as L. leichmannii. A representative group A isolate colonized the surface of the nonsecretory epithelium of the stomach of gnotobiotic mice; a group D isolate did not.

Agglutination↗

Influence of certain indigenous gastrointestinal microorganisms on duodenal alkaline phosphatase in mice.

Alkaline phosphatase activity was assayed in duodenal homogenates or extracts from adult specific pathogen-free (SPF) and germfree mice and gnotobiotic mice monoassociated with a Lactobacillus sp., a Bacteroides sp., or a coliform strain indigenous to SPF mice. Activity levels of the enzyme were much higher in the preparations from germfree mice than in those from the SPF controls. In the gnotobiotes monoassociated either with a freshly isolated Lactobacillus sp. or a Bacteroides sp., the levels of alkaline phosphatase activity were intermediate between the values for germfree and SPF mice. By contrast, in the gnotobiotes monoassociated with a coliform strain, alkaline phosphatase activity remained at high germfree levels. Butanol extracts of duodenal tissue from SPF mice, germfree mice, and exgermfree mice associated with an indigenous microflora from SPF mice (conventionalized) were subjected to acrylamide gel electrophoresis. A stain for alkaline phosphatase activity revealed three major bands in the gels prepared with extracts from SPF and conventionalized mice, but only two in the gels prepared with extracts from germfree mice. All three bands may have been present in the latter gels. One of the bands (the middle one) may have been obscured, however, by high activity in the slowest moving band. As determined by densitometric scanning, the slowest moving band had much higher activity in the preparations from germfree animals than in those from SPF or conventionalized mice. These findings suggest that the indigenous microbial flora affects not only quantitatively, but also qualitatively, the activity of alkaline phosphatases in the mouse intestinal mucosa.

Alkaline Phosphatase↗

Indigenous microorganisms prevent reduction in cecal size induced by Salmonella typhimurium in vaccinated gnotobiotic mice.

Germfree CD-1 mice challenged by the oral route with Salmonella typhimurium had ceca that were abnormal in appearance and reduced in size compared to those of germfree controls. Similarly, germfree mice injected with heat-killed S. typhimurium or gnotobiotes associated with three indigenous microbes (Lactobacillus, Bacteroides, Clostridium), and subsequently challenged with S. typhimurium also had small ceca. By contrast, gnotobiotic mice that had been both injected with the heat-killed S. typhimurium and associated with the three indigenous microbes before challenge with S. typhimurium had ceca similar in size and appearance to germfree mice. Thus, indigenous microorganisms could interfere with the mechanism by which the pathogen induced the decrease in cecal size, but could do so only in mice injected with heat-killed bacteria. This phenomenon suggests synergism between the interference effected by the indigenous bacteria and the resistance mechanisms of the animal.

Animals↗

Effect of penicillin on the succession, attachment, and morphology of segmented, filamentous microbes in the murine small bowel.

Indigenous segmented filamentous microbes attach to murine ileal epithelial cells. These microbes can be seen on the epithelial surface with a scanning electron microscope. They colonize preferentially the distal ileum in mice. Penicillin, placed in the animal's drinking water, eliminates the microbes from the mouse ileum, but recolinization of the ileum is observed 4 to 5 weeks after the penicillin treatment is stopped. Within 3 to 5 h after rats are given penicillin, the morphology of the microbes is changed. Their external surfaces are wrinkled or broken. Vacated and partially vacated attachment sites are observed. Almost all of the organisms disappear from murine ilea after the animals are exposed to penicillin for 10 h. These observations are discussed in relation to the microbe itself and in its interaction with ileal epithelial cells.

Animals↗

Influence of the indigenous gastrointestinal microbial flora on duodenal Mg2+ -dependent and (Na+ + K+) -stimulated adenosine triphosphatase activities in mice.

Mg-dependent and (Na+ + K+)-stimulated adenosine triphosphatase (ATP-ase) activities were assayed in butanol extracts of duodenal tissue from germ-free, specific-pathogen-free, and ex-germfree mice associated with an indigenous microflora from specific-pathogen-free mice. In the germfree mice the levels of both ATPase activities were significantly higher than the levels in specific-pathogen-free mice. By contrast, the ex-germfree animals colonized by an entire indigenous microflora, the values fell to levels close to those for specific-pathogen-free animals. (Na+ + K+)-stimulated ATPase was not inhibited by ouabain in extracts from any of the three kinds of mice. These findings show that the indigenous microbial flora influences the intestinal ATPase activity of mice and, because of the connection between (Na+ + K+-stimulate ATPase and active transpoort, undoubtedly affects the process of absorption in the intestinal tract.

Adenosine Triphosphatases↗

Controlled trial of therapy in covert bacteriuria of childhood.

Sixty-three girls with covert bacteriuria were included in a controlled trial of therapy. Recurrent infection in the treated group was common and was not significantly different from the rate of persistent infection in the untreated control group. Two children in each group developed clinical pyelonephritis; the others have remained healthy and all of them have a normal rate of growth. 2 years after diagnosis three of the thirty-four children in the control group and one of twenty-six children in the treated group have radiological evidence of new scars of pyelonephritis. These changes were relatively minor and in both groups of children renal growth was similar to that in normal children. It is suggested that for most of these children therapy is not essential, and that when renal changes occur they are of little or no significance. Prescriptive screening for cobert bacteriuria of childhood cannot be recommended at present.

Ampicillin↗

Immune responses of specific pathogen-free and gnotobiotic mice to antigens of indigenous and nonindigenous microorganisms.

Strains of indigenous Escherichia coli, Bacteroides, and Lactobacillus were isolated from the gastrointestinal tracts of specific pathogen-free (SPF) mice. Nonvaccinated SPF mice exhibited in their spleens low numbers of plaque-forming cells (PFC) and rosette-forming cells reacting with antigens of these andigenous bacteria. PFC reacting with these bacterial antigens were not detected in infant SPF mice until 7 days after birth. Compared with nonvaccinated controls, SPF mice vaccinated parenterally with indigenous E. coli or Bacteroides produced a moderate increase in the numbers of specific PFC. Thus, the SPF mouse is capable of responding immunologically after vaccination with microbes indigenous to its intestinal tract. However, more PFC reacting with homologous vaccine antigens were detected after parenteral vaccination of SPF mice with nonindigenous E. coli O127:B8, E.coli O14, or B. fragilis than after parenteral vaccination with indigenous E. coli or Bacteroides. Gnotobiotic mice orally monoassociated with these nonindigenous bacteria exhibited greater immune responses to antigens of the bacteria used to monoassociation than did gnotobiotes monoassociated with the indigenous microbes. The results are consistent with the hypothesis that mice are more responsive immunologically to antigens of nonindigenous bacteria than they are to antigens of certain microbes indigenous to their gastrointestinal tracts.

Animals↗

Association of Salmonella typhimurium with, and its invasion of, the ileal mucosa in mice.

A wild-type strain of Salmonella typhimurium and three mutant rough colonial variants of the wild type were compared for their ability to become associated with and invade the ileal mucosa of germfree and specific-pathogen-free mice. The rough-mutant strains differed from the wild type in having incomplete lipopolysaccharides lacking one or more sugars in the polysaccharide moiety. The wild-type and mutant strains also differed one from the other in the types of appendages (flagella, pili) on their surfaces. Depending upon the dosage of bacteria given, all mutant strains as well as the wild type could associate with and invade the intestinal mucosa of infected gnotobiotic mice. If the infecting dosage was high enough, at least two of the mutant strains and the wild type invade the intestinal mucosa of the specific-pathogen-free animals. O antigen, flagella, or pili do not appear to be essential for the association of S. typhimurium with the mucosal surface of the mouse ileum. O antigen on the bacterial cell surface may be important, but not essential, for invasion of the ileal mucosa.

Animals↗