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Biomedical subjects

D Horton

Publications and source records attributed to D Horton.

At least 37 records · Page 2Linked to original sources

Multiple cerebral haematomata and peripheral nerve palsies associated with a case of juvenile diabetic ketoacidosis.

A 15-year-old girl presented de novo in diabetic ketoacidosis having been comatose for 24 h (day 1). A CT scan and lumbar puncture performed on admission were normal and her conscious level slowly improved over several days. On day 7 she had central neurological signs of bilateral knee clonus and an extensor plantar response. In addition, she had developed lower motor neurological signs of an ulnar nerve palsy of the left forearm, and ulnar, median, and radial nerve palsies of the right forearm. Magnetic resonance imaging (MRI), performed on day 12, showed multiple small cerebral haematomata with appearances at least several days of age. The scattered lesions were localized particularly to the parieto-occipital region, with sparing of the basal ganglia and without cerebral oedema, a novel feature not previously described in juvenile ketoacidosis. Four months later there was minimal residual disability of her right arm. The clinical findings together with the MRI images suggested that the peripheral nerve and central lesions were temporally related, suggesting a common aetiology. However, it is likely that MRI showed cerebral lesions which may have been missed by the conventional CT scanning performed initially.

Adolescent↗

Magnetic resonance imaging of radiation dose distributions using a polymer-gel dosimeter.

A new formulation of a tissue-equivalent polymer-gel dosimeter for the measurement of three-dimensional dose distributions of ionizing radiation has been developed. It is composed of aqueous gelatin infused with acrylamide and N, N'-methylene-bisacrylamide monomers, and made hypoxic by nitrogen saturation. Irradiation of the gel, referred to as BANG, causes localized polymerization of the monomers, which, in turn, reduces the transverse NMR relaxation times of water protons. The dose dependence of the NMR transverse relaxation rate, R2, is reproducible (less than 2% variation) and is linear up to about 8 Gy, with a slope of 0.25 s(-1)Gy(-1) at 1.5 T. Magnetic resonance imaging may be used to obtain accurate three-dimensional dose distributions with high spatial resolution. Since the radiation-induced polymers do not diffuse through the gelatin matrix, the dose distributions recorded by BANG gels are stable for long periods of time, and may be used to measure low-activity radioactive sources. Since the light-scattering properties of the polymerized regions are different from those of the clear, non-irradiated regions, the dose distributions are visible, and their optical densities are dependent on dose.

Acrylic Resins↗

Composition and Rheological Properties of Extracellular Polysaccharide 105-4 Produced by Pseudomonas sp. Strain ATCC 53923.

A soil isolate produced a novel extracellular polysaccharide (EPS) with unusually potent thickening powers. The EPS contained d-mannose, d-glucose, d-galactose, and d-glucuronic acid in the unique molar ratio 1:4:1:2 and 10 to 15% acetate. Viscosities of a 1-g/liter aqueous solution were 1 x 10 and 14 x 10 cP at shear rates of 0.01 and 0.1 s, respectively. The EPS was insensitive to high concentrations of NaCl and CaCl(2).

Journal Article↗

Wittig reaction of unprotected D-aldopentoses with stabilized ylides: metal-ion effects.

Each of the four D-aldopentoses (1-4) reacts in the unprotected form with Ph3PCHCO2Me (5) in THF to give stereoselectively the corresponding trans-alpha,beta-unsaturated C7 Wittig adducts, isolated as the corresponding 4,5,6,7-tetraacetates (7-10) or 4,5:6,7-di-O-isopropylidene derivatives (11-14). Concurrently formed are also bicyclic, 1,4-lactone derivatives, isolated as their 5,7-diacetates (15-18) or 5,7-O-isopropylidene derivatives (19), arising through intramolecular Michael addition from the initial acyclic adducts. Formation of the cyclized products is suppressed by incorporation of Cu(OAc)2 in the reaction mixture, permitting preparative isolation of the hept-3-enonate derivatives 7-10, useful as dienophiles in Diels-Alder carbocyclizations with chirality transfer. Optimized yields were 25% (D-ribo), 50% (D-arabino), 49% (D-xylo), and 61% (D-lyxo). Under Cu(OAc)2-catalyzed conditions, the formation of small proportions of 3,7-anhydroheptonic acid esters (21 and 23) was observed in the D-arabino and D-xylo series, but not with the other two pentoses.

Carbohydrate Conformation↗

Stereocontrol in Diels-Alder cycloaddition to unsaturated sugars: reactivities of acyclic seven-carbon trans dienophiles derived from aldopentoses.

Acyclic trans-2,3-unsaturated aldoheptonate derivatives (1-9) obtained from D-aldopentoses by Wittig chain-extension served as dienophiles for a detailed comparative study of their asymmetric Diels-Alder cycloaddition with cyclopentadiene. Cycloaddition under uncatalyzed thermal conditions gave mixtures of the four possible stereoisomeric norbornene adducts. The endo:exo ratios and the diastereofacial selectivities in the formation of the adducts were determined by NMR spectroscopy and by chemical transformations. The quantitative distribution of adducts as a function of stereochemistry of the dienophile is discussed.

Carbohydrate Conformation↗

Stereocontrol in Diels-Alder cycloaddition to unsaturated sugars: reactivities of cis-dienophiles with cyclopentadiene.

Cycloaddition of cyclopentadiene with a D-arabinose-derived cis-dienophile, methyl (Z)-4,5,6,7-tetra-O-acetyl-2,3-dideoxy-D-arabino-hept-2-enonate (2), under thermal conditions gave essentially a single norbornene adduct, isolated crystalline in 81% yield and identified by NMR spectroscopy and X-ray crystallography as methyl (5R,6S)-6-endo-(1,2,3,4-tetra-O-acetyl-D-arabino-tetritol-1-yl)bic yclo [2.2.1]-hept-2-ene-5-endo-carboxylate (3). The diene adds exclusively from the si-face of the dienophile and give only the endo product. The same sequence starting from L-arabinose gave the enantiomer (7) of 3. In contrast, a related cis-dienophile (9) having a butenolide ring reacts with cyclopentadiene from the opposite (re) face giving mainly the endo adduct (5S,6R)-6-endo-(2,3,4-tri-O-acetyl)-D-arabino-tetritol-1-yl)bicycl o [2.2.1]hept-2-ene-5-endo-carboxylic acid 1,4-lactone (10), isolated crystalline in 70% yield, whose structure was again established by NMR spectroscopy, and firmly consolidated by X-ray crystallography. The minor (11%) product was the exo(5S,6R) isomer 11. A cis-enonate 14, analogous to 2 but deoxygenated at the allylic position, showed negligible diastereofacial selectivity and reacted with cyclopentadiene to give a mixture of all four possible adducts. A 6-membered ring dienophile 16 was also subjected to the same cycloaddition for comparison with the butenolide 9; it gave principally the two endo products 17 and 19 in 31 and 38% yields, respectively, accompanied by 12% of a mixture of the two exo products (18 and 20). The quantitative distribution of cycloaddition products as a function of dienophile stereochemistry is discussed. The high degree of asymmetric induction observed, especially with the readily accessible dienophiles 2 and 7, provides a valuable route of access to enantiomerically pure tetra-C-substituted cycloalkanes.

Carbohydrate Conformation↗

Synthesis of 3-deoxyaldulosonic acid esters by one-carbon chain extension of glycal-derived lactone precursors.

A convenient preparative route is described for 3-deoxyaldulosonic acids. Glycal precursors are oxidatively converted into 2-deoxyaldonolactones, which react with 1,3-dithian-2-yl anion to afford 1,3-propanediyl dithioacetals of higher 3-deoxyaldosuloses. Deprotection with mercuric salts in wet or dry alcohols gave high yields of the corresponding alkyl aldulosonates. Preparative reaction conditions were optimized and the anomeric configurations of the ketopyranose products were established by 13C NMR.

Deoxy Sugars↗

Glycosylated derivatives of benzophenone, benzhydrol, and benzhydril as potential venous antithrombotic agents.

A series of glycosylated derivatives of benzophenone, benzhydrol, and benzhydril has been synthesized and evaluated for potential activity as venous antithrombotic agents. Studies on structure-activity relationships revealed that compounds having an electron-withdrawing group in the benzhydril or benzhydrol moiety, and specifically those having the beta-D-xylopyranosyl structure in the sugar moiety, were good antithrombotic agents in a rat model of venous thrombosis.

Administration, Oral↗

Synthesis and antitumor activity of anthracycline disaccharide glycosides containing daunosamine.

Daunosamine, as its 4-O-acetyl-3-N-trifluoroacetyl glycosyl chloride derivative (1b), has been coupled alpha-L-glycosidically to the 3- and 4-mono-O-acetyl derivatives of L-rhamnal to afford disaccharide glycal derivatives, whose conversion into the corresponding 2-deoxyglycosides by sequential alkoxyiodination-tributylstannane reduction has been evaluated. The sequence successfully demonstrated with the methyl glycosides was successfully extended with daunomycinone as the aglycon, providing a preparative route to 7-O-[3-O-(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)- 2,6-dideoxy-alpha-L-arabino-hexopyranosyl]daunomycinone hydrochloride (15), an analogue of natural anthracycline antibiotics containing daunosamine and a 2,6-dideoxy-L-hexose.

Aminoglycosides↗

Audit in action: significant reduction of double-contrast barium enema screening time with no loss of examination quality.

The double-contrast barium enema is an examination of high radiation exposure to the patient. As part of a departmental audit, our own fluoroscopic screening times were being recorded. A study was undertaken to see if a determined effort could reduce the screening time without having a detrimental effect on the quality of the examinations. Methods of screening time reduction were identified and then implemented by two radiologists. In the period before the study the average screening time for radiologists A and B was 2.6 min and 3.2 min, respectively (over 56 examinations). After implementation of the changes, the average screening time for both was 0.9 min (over 50 examinations). This is a statistically significant reduction (p less than 0.01). The examinations were assessed independently by a gastroradiologist. No difference in the quality of the examinations was identified. We conclude that a significant reduction of screening time for the double-contrast barium enema can be achieved without loss of examination quality.

Barium Sulfate↗

Transformations of unsaturated acyclic sugars into enantiomerically pure norbornene derivatives.

The C7 acyclic unsaturated-sugar ester 1, derived from L-arabinose, and its enantiomer serve as convenient dieneophiles for chirality transfer for synthesis of optically pure carbocyclic derivatives through cycloaddition reactions. Reaction of 1 with cyclopentadiene may be controlled to give preparative access to the 5,6-disubstituted norbornene adducts 4a, 5a, and 7a, according to the conditions used. The distribution of the four possible isomeric products from this cycloaddition was quantitated, and the effect of substitutional variation on the precursor dienophile 1 was also examined. Adducts 4a and 5a were transformed into such substituted carbocycles of known absolute configuration as the methyl esters (11 and 12) of norbornene (bicyclo[2.2.1]hept-2-ene)-6-carboxylic acid and nortricyclane (tricyclo[2.2.1.0(2,6)]heptane)-3-carboxy acid in optically pure form, specifically through decarbonylation reactions using RhCl(PPh3)3 (Wilkinson's complex) and [Rh(dppp)2]Cl[dppp = Ph2P(CH2)3PPh2]. The optical purity of 12 was established by the use of a chiral lanthanide shift-reagent.

Carbohydrate Conformation↗

Synthesis of optically pure di- to tetra-substituted cyclopentanes from sugar-derived norbornene derivatives.

The chiral norbornene derivative 2 obtained from Lewis acid-catalyzed reaction of an L-arabinose-derived dienophile 1 and cyclopentadiene was oxidized with OsO4-NaIO4 to the dialdehyde 3, a tetrasubstituted cyclopentane. Mild treatment of 3 with [Rh(dppp)2]Cl [dppp = Ph2P(CH2)3PPh2] (4) selectively epimerized the aldehyde adjacent to the methoxycarbonyl group to give the epi-aldehyde 8. Under more vigorous conditions, this group was decarbonylated to give the monoaldehyde 11, and more strenuous treatment removed the second aldehyde group to give the didecarbonylated cyclopentane derivative 5. The structure and optical purity of 5 was confirmed by its transformation into (1S,2S)-cyclopentane-1,2-dicarboxylic acid (7).

Carbohydrates↗

Radiation therapy of pituitary tumors: results in 95 cases.

Between 1967 and 1985 95 patients with pituitary adenoma received radiation therapy at the University of California, Los Angeles (UCLA), and the West Los Angeles Veterans' Administration (VA) Medical Center. Seventy of these patients received radiation therapy immediately as adjuvant therapy following incomplete resection, and 25 were irradiated as primary treatment or after surgical failure. The majority of cases (87%) presented clinically with macroadenomas. Two-thirds of the patients were treated with parallel opposed lateral portals to a midline total dose of 50 Gy. The mean follow-up was 7 years (range: 30-250 months). In our series, there is a difference in response by disease subtype. The control rates were 83% (30 of 36) for nonfunctioning adenoma, 60% (nine of 15) for growth-hormone secreting adenoma, 44% (16 of 36) for prolactin secreting adenoma, three of five for Nelson's syndrome, and three of three for Cushing's disease. There was a tendency for a better response rate with a total dose of greater than or equal to 50 Gy for prolactinoma. None of the patients were known to develop brain necrosis or radiation-induced sarcoma. An analysis of these results and a review of the literature is presented here.

Acromegaly↗

Iodoalkoxylation of 1,5-anhydro-2-deoxy-hex-1-enitols (glycals).

Exclusive trans-addition is observed in the iodoalkoxylation of the 6-membered cyclic enol ethers 3,4-di-O-acetyl-L-rhamnal (1), 3,4-di-O-acetyl-L-fucal (2), and related glycal derivatives. The main products from 1 and from 3,4,6-tri-O-acetyl-D-glucal (3) thus had the alpha-manno configuration. Similarly, alpha-talo products were obtained from 2 in 87-93% yield. The product distribution is not affected by the electronegativity of the 5-substituent. It is concluded that steric factors in the glycal and the nucleophile affect only the step of trans-diaxial opening of the intermediate iodonium ion. Enhanced yields of the desired trans-diaxial products were observed in reactions of glycals having the lyxo configuration when the reactions were conducted in tetrahydrofuran or methanol.

Alkylation↗

Shunt-related brain abscess and ascending shunt infection.

We report the fifth case of shunt-related brain abscess. Two prior cases have been associated with colonic perforation and infection with gram-negative enteric organisms. These cases strongly suggest that ascending shunt infection is possible despite bulk cerebrospinal fluid flow in the opposite direction and add to our understanding of shunt infections.

Brain Abscess↗