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Biomedical subjects

C Middleton

Publications and source records attributed to C Middleton.

At least 19 recordsLinked to original sources
PubMed2006

Stump ulcers and continued prosthetic limb use.

Stump ulcers are common problems in amputees. Temporary discontinuation of prosthetic limb use is frequently employed to facilitate healing. Inevitably, this limits activity and may, for instance, prevent an amputee from going to work. A survey of clinical practice was carried out based on the premise that controlled continued prosthetic limb use in patients with stump ulcers will not adversely affect the ulcer nor prevent healing. The survey would also form a basis for developing future guidelines in the management of stump ulcers. All consecutive patients attending the Chapel Allerton Hospital prosthetic clinic between January 2003 and May 2004 with stump ulcers were recruited into the study. Primary outcome measures were changes in the surface area of the ulcers and in clinical photographs taken on 2 occasions 6 weeks apart. Some 102 patients with a mean age 60 years (range 18 - 88 years) were recruited. Eight patients who were established prosthetic limb users did not complete the study and were excluded from the analysis. Of the patients 52 were newly referred patients with delayed surgical wound healing while 42 were established prosthetic limb users for at least 1 year. Continued prosthetic limb was associated with a significant reduction in ulcer size (p < 0.05). Mean sizes of the ulcers at first and second observations were 3.30 cm2 (range 0.06 - 81) and 0.70 cm2 (range 0.00 - 13.00) respectively. The ulcers improved in 83 cases while two were unchanged. Deterioration was observed in nine cases. The current clinical practice is to allow most of the patients to commence or continue prosthetic limb wearing despite the presence of stump ulceration. This observational study found that, despite prosthetic use, 60 (64%) cases healed completely within the six-week study period and 23 (25%) ulcers reduced in size. The ulcers were unchanged in 2% of the cases. Deterioration was observed in nine (9%) cases. This survey suggests that the current practice of allowing patients to use their prostheses is safe. A clinical trial is now needed to establish whether this practice alters healing rate or has any other disadvantages for new or established amputees.

Adolescent↗
PubMed2001

Conformation and orientation of the retinyl chromophore in rhodopsin: a critical evaluation of recent NMR data on the basis of theoretical calculations results in a minimum energy structure consistent with all experimental data.

In the absence of a high-resolution diffraction structure, the orientation and conformation of the protonated Schiffs base retinylidinium chromophore of rhodopsin within the opsin matrix has been the subject of much speculation. There have been two recent reliable and precise NMR results that bear on this issue. One involves a determination of the C20-C10 and C20-C11 distances by Verdegem et al. [Biochemistry 38, 11316-11324 (1999)]. The other is the determination of the orientation of the methine C to methyl group vectors C5-C18, C9-C19, and C13-C20 relative to the membrane normal by Gröbner et al. [Nature 405 (6788), 810-813 (2000)]. Using molecular orbital methods that include extensive configuration interaction, we have determined what we propose to be the minimum energy conformation of this chromophore. The above NMR results permit us to check this structure in the C10-C11=C12-C13 region and then to check the global structure via the relative orientation of the three C18, C19, and C20 methyl groups. This method provides a detailed structure and also the orientation for the retinyl chromophore relative to the membrane normal and argues strongly that the protein does not appreciably alter the chromophore geometry from its minimum energy configuration that is nearly planar s-trans at the 6-7 bond. Finally, the chromophore structure and orientation presented in the recently published X-ray diffraction structure is compared with our proposed structure and with the deuterium NMR results.

Animals↗
PubMed1991

Histologic comparison of regeneration in human intrabony defects when osteogenin is combined with demineralized freeze-dried bone allograft and with purified bovine collagen.

A bone-inductive protein, osteogenin, has been isolated from long bones of humans and offers promise as a grafting material. Studies, however, suggest that osteogenin must be combined with a bone-derived matrix in order to initiate bone differentiation. The purpose of this study was to determine if osteogenin combined with demineralized freeze dried bone allograft (DFDBA), a bone-derived matrix, and with a bovine tendon-derived matrix will enhanced regeneration of intrabony defects in humans. The tendon-derived matrix and DFDBA used alone served as controls. The ability of each material to form a new attachment apparatus was evaluated independently in submerged and nonsubmerged environments in 2 patient populations. Lymphocyte testing was performed to assess development of an immune reaction to osteogenin. The most apical level of calculus on the root served as the histologic reference point to measure regeneration. Biopsies were obtained at 6 months and regeneration was measured histomorphometrically by 2 blinded evaluators. Serial sections from 36 submerged defects in 8 patients and 50 nonsubmerged defects in 6 patients were submitted for statistical analysis. Mean results indicate that osteogenin combined with DFDBA significantly enhanced regeneration of a new attachment apparatus and component tissues in a submerged environment. DFDBA plus osteogenin and DFDBA alone formed significantly more new attachment apparatus and component tissues than either the tendon-derived matrix plus osteogenin or the tendon-derived matrix alone in both submerged and nonsubmerged environments. There were no significant differences between the tendon-derived matrix plus osteogenin and the tendon-derived matrix alone in either the submerged or nonsubmerged environment. Osteogenin does not impair normal lymphocyte blastogenesis at 6 months postsurgical challenge.

Alveolar Bone Loss↗
PubMed1989

Danazol and hepatic neoplasia: a case report.

Although hepatic side-effects of danazol are well known, the occurrence of hepatic tumours is not well documented. We report a case of hepatocellular adenoma occurring in a 35-year-old woman with endometriosis who had been taking danazol over a three year period.

Adult↗
PubMed1987

Effects of lead acetate on DNA and RNA synthesis by intact HeLa cells, isolated nuclei and purified polymerases.

The effects of lead acetate on DNA and RNA synthesis have been investigated with intact HeLa cells, isolated nuclei, and purified DNA and RNA polymerases. No inhibition of DNA or RNA synthesis in intact cells was found even after exposure to 0.5 mM lead acetate for 18 hr. In contrast, both DNA and RNA synthesis in isolated nuclei were inhibited by lead (with 50% inhibition at approximately 150 and 80 microM respectively). Similarly, both HeLa DNA polymerase alpha and RNA polymerase II were inhibited, with 50% inhibition obtained at approximately 150 and 20 microM lead acetate respectively. The inhibition of nucleic acid synthesis in isolated nuclei can thus be accounted for by inhibition of the polymerases. The sensitivity of Escherichia coli DNA polymerase I to lead acetate was found to be significantly greater than the HeLa DNA polymerase alpha (50% inhibition at only 10 microM), but the sensitivity of the E. coli RNA polymerase was the same as that of the HeLa enzyme.

DNA Replication↗
PubMed1987

Malassezia furfur fungemia as a treatable cause of obscure fever in a leukemia patient receiving parenteral nutrition.

We describe a 46-year-old man with acute non-lymphocytic leukemia (ANLL) and Crohn's disease who, while receiving total parenteral nutrition (TPN), developed a protracted febrile illness with thrombocytopenia, pulmonary infiltrates and jaundice. Malassezia furfur, a lipophilic fungus, was identified from blood culture on lipid-enriched media. The patient improved rapidly with cessation of TPN and removal of his central venous catheter. M. furfur may cause a severe illness in immunosuppressed patients receiving TPN.

Acute Disease↗
PubMed1987

Inhibition of RNA and DNA polymerases by the product of the reaction of selenite with sulfhydryl compounds.

Sodium selenite has previously been shown to inhibit DNA and RNA synthesis in both intact cells and isolated nuclei. Nevertheless, DNA and RNA polymerases, the enzymes responsible for this synthesis, are insensitive to inhibition by selenite. Several DNA and RNA polymerases have now been shown to be inhibited by selenite in the presence of sulfhydryl compounds. This inhibition is due to the reaction of selenite with the sulfhydryl compounds to form selenotrisulfide derivatives which inhibit the enzymes. The selenotrisulfides decrease the Vmax of the polymerase reaction and increase the apparent Km for the triphosphates, but do not alter the apparent Km of the enzyme for the DNA template. There are differences in potency between selenotrisulfides formed from similar sulfhydryl compounds such as mercaptoethanol and mercaptoethylamine. There are also differences in the sensitivity of different polymerases to inhibition by the selenotrisulfides.

Chemical Phenomena↗
PubMed1985

Crypts, villi and microvilli in the small intestine of the rat. A stereological study of their variability within and between animals.

Small intestines from normal adult rats were quantified by optical and electron microscopy using stereological principles devised for the purpose. Five segments per bowel were examined. Baseline data characterising villi, microvilli and crypts of Lieberkühn were used to study differences between segments and between animals. Intestines fixed by in situ perfusion had, on average, 100 cm2 of primary mucosa. This basic surface was amplified to 500 cm2 by villi and to 1 m2 by the microvilli of enterocytes. Villous and microvillous surface areas may scale to body weight in the same way as metabolic requirements. Proximodistal gradients in mucosal architecture existed for the volumes and surface areas of villi and for the numbers, lengths, diameters and surface areas of microvilli. Most variables were higher proximally and declined towards the terminal ileum. The volume of crypts stayed constant throughout the entire intestine and ratios between villous dimensions (volumes and surface areas) and crypt volume did not vary between animals. Findings are discussed in the context of regional differences in bowel function and of their relevance to studies of epithelial kinetics.

Animals↗
PubMed1984

Immunohistochemical localization of corticotropin releasing factor (CRF) in the hypothalamus of the squirrel monkey, Saimiri sciureus.

Corticotropin releasing factor immunoreactive (CRF-IR) neuronal cell bodies and fibers have been localized in both the paraventricular and supraoptic nuclei of the hypothalamus of the squirrel monkey. The major projection from these nuclei is to the median eminence and neural stem. A few CRF-IR fibers were found in the dorsal pars nervosa primarily adjacent to the pars intermedia. A rostral projection of CRF-IR fibers is associated with the suprachiasmatic nucleus and continues to septal areas. A caudally projecting bundle of fibers was observed entering the midbrain in neuropil adjacent to the aqueduct. The location of CRF-IR components is also compared with those containing vasopressin (AVP).

Animals↗
PubMed1982

Fine structure of Periplaneta americana neurons in long-term culture.

A new culture technique is described for dissociated ganglia of embryos of Periplaneta americana. Neurons obtained by the mechanical dissociation of ganglia from 23-26 day old embryos were grown for seven days in a combination of Schneider's Drosophila Medium and Eagle's Basal Medium and then transferred to a combination of Leibovitz's L-15 Medium and Yunker's Modified Grace's Medium supplemented with ecdysone. Neurons cultured in this way survived for periods in excess of one month. The cells had a typically neuronal ultrastructure and produced axonal processes that associated to form fibre bundles. Within these processes neurosecretory granules, dense-core vesicles and clear vesicles were found. In some instances these vesicles aggregated at points of contact between fibres giving the appearance of presynaptic endings. These cultures would appear to be suitable for pharmacological studies of the insect nervous system.

Animals↗
PubMed1981

Gadusol, an enolic derivative of cyclohexane-1,3-dione present in the roes of cod and other marine fish. Isolation, properties and occurrence compared with ascorbic acid.

Gadusol, C8H12O6, has been isolated from roes of the cod (Gadus morhua L.), i.e., ovaries that contain ripe eggs just before spawning. The concentration is about 4 g/kg dry wt. It has been identified as 1,4,5-trihydroxy-5-hydroxymethyl-2-methoxycyclo-hex-1-en-3-one and this structure was confirmed by synthesis of the anhydro tetra-acetate derivative from methyl 3,5-diacetoxy-4-methoxybenzoate. Concentrations of gadusol in the roes of other marine teleost fish examined are of the same order as in cod roes. Gadusol has some properties similar to ascorbic acid and both compounds, after oxidation, react with 2,4-dinitrophenylhydrazine in the commonly-used assay procedure for ascorbic acid. Specific assays showed that the concentrations of gadusol in the roes of marine fish are severalfold greater than those of ascorbic acid. Gadusol is structurally related to the mycosporines previously reported from a number of different organisms.

Animals↗
PubMed1980

Role of alcohol in the aetiology of hypertension.

Hypertension is a common condition facing medical practitioners on a day-to-day basis, yet much is to be learnt regarding its cause. Excess alcohol intake has been recognized by clinicians as a causal factor on an anecdotal basis for many years now. Little evidence for this has been provided from statistical analysis of formal studies. On this basis, a study was undertaken in a population of 85 adult males to see if any correlations could be drawn between alcohol intake and standard blood pressure readings, taking into account as many other variables as possible which may contribute to blood pressure, such as age, body weight and smoking habits. In this study, a statistically significant relationship between alcohol intake and blood pressure is demonstrated, indicating a need for further investigation in this field.

Adult↗
PubMed1980

Regulation of sterol synthesis in human intestinal mucosa.

The effect of dietary factors and experimental manipulations designed to perturb the enterohepatic circulation on the rate of sterol synthesis were studied in freshly isolated human jejunal mucosa from normal subjects. Fasting significantly reduced the rate of sterol synthesis from [14C]acetate in jejunal mucosa obtained from normolipaemic obese subjects. A high cholesterol diet had no consistent effect on the synthesis in normal subjects. Administration of cholestyramine resulted in a marked rise in the incorporation of [14C]acetate into sterols, while the administration of chenodeoxycholic acid did not significantly reduce basal sterol synthesis in normal subjects. These results demonstrate that in man the rate of sterol synthesis in intestinal mucosa is altered in response to physiological variables. Although these findings indicate that sterol synthesis in this tissue is subject to regulation, no difference was observed in basal sterol synthesis between normal subjects and patients heterozygous for familial hypercholesterolaemia.

Administration, Oral↗
PubMed1976

Studies on the nutrition of marine flatfish. The effect of different dietary fatty acids on the growth and fatty acid composition of turbot (Scophthalmus maximus).

1. Five groups of juvenile turbot (Scophthalmus maximus) which had been given a diet free of fat for 12 weeks were given diets in which the lipid component (g/kg) was: oleic acid alone 50, oleic acid 40+linoleic acid 10, oleic acid 40+linolenic acid 10, oleic acid40+arachidonic acid 10 or oleic acid 40+cod-liver oil 10. These five experimental diets were given for 16 weeks. 2. Weight gains were highest in the group given the diet containing cod-liver oil and lowest in the groups given diets containing oleic acid alone or oleic acid+linoleic acid. Weight gains in the groups given oleic acid+arachidonic acid or linolenic acid were markedly inferior to those of the group given oleic acid+cod-liver oil. It is concluded that arachidonic acid is inferior to polyunsaturated fatty acids of the omega3 series in maintaining growth rate in turbot. 3. Fatty acid analyses of neutral lipids and phospholipids of liver and extrahepatic tissues did not suggest any evidence of desaturation of dietary oleic acid, linoleic acid or linolenic acid by the turbot. These experiments confirm previous isotopic evidence that turbot lack the necessary microsomal desaturases to perform this metabolic transformation.

Animals↗
PubMed1975

Elongation and desaturation of dietary fatty acids in turbot Scophtalmus maximus L., and rainbow trout, Salmo gairdnerii rich.

Turbot and rainbow trout, which had previously recieved diets free of fat, were fed [1-14C] fatty acids. The distribution of radioactivity in the tissue fatty acids was examined 6 days later. In rainbow trout fed [1-14C] 18:3omega3, 70% of the radioactivity was present in 22:6omega3 fatty acid. In contrast, turbot fed [1-14C] 18:1omega9, 18:2omega6, or 18:3omega3 converted only small amounts of labeled fatty acids (3-15%) into fatty acids of longer chain length. The major product of the limited modification found in turbot was the dietary acid elongated by 2 carbon atoms.

Animals↗