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Biomedical subjects

Andrew Taylor

Publications and source records attributed to Andrew Taylor.

33 records · Page 2Linked to original sources
PubMed2004

Influence of diet on iron, copper, and zinc status in children under 24 months of age.

The objective of the study was to determine whether iron and micronutrient status is improved with an increased amount of meat in the diet. To this end, a longitudinal prospective study with infants recruited at 4 mo and followed until 24 mo of age was undertaken. One hundred ninety-eight infants formed the original study cohort; 48 withdrew before the end of the study. Subjects were classified as nonmeat eaters or as mixed (red and white)-meat eaters subgrouped into tertiles depending on the meat content reported in diet diaries. Seven-day weighed food records were recorded at 4, 8, 12, 16, 20, and 24 mo. Blood samples taken at 4, 12, and 24 mo were analyzed for parameters of iron and micronutrient status. Iron intake increased during the first year, thereafter remaining constant. The percentages of subjects with hemoglobin values below 110 g/L were 34.1, 23.1, and 13.4 at 4, 12, and 24 mo, respectively. For parameters of iron status, the number of results below the reference range was determined for each diet group and a significant negative relationship between serum iron and meat intake at 12 mo of age was seen (p<0.023). There was a trend for hemoglobin concentrations to be inversely related to the meat intake, at the same age (p<0.068). No effects on zinc or copper status were seen. We conclude that a weak association between dietary meat and iron/Hb suggests a positive role for red meat. There was no disadvantage to the nonmeat-eating infants with respect to zinc or copper.

Aging↗
PubMed2003

The role of metals in neurodegenerative processes: aluminum, manganese, and zinc.

Until the last decade, little attention was given by the neuroscience community to the neurometabolism of metals. However, the neurobiology of heavy metals is now receiving growing interest, since it has been linked to major neurodegenerative diseases. In the present review some metals that could possibly be involved in neurodegeneration are discussed. Two of them, manganese and zinc, are essential metals while aluminum is non-essential. Aluminum has long been known as a neurotoxic agent. It is an etiopathogenic factor in diseases related to long-term dialysis treatment, and it has been controversially invoked as an aggravating factor or cofactor in Alzheimer's disease as well as in other neurodegenerative diseases. Manganese exposure can play an important role in causing Parkinsonian disturbances, possibly enhancing physiological aging of the brain in conjunction with genetic predisposition. An increased environmental burden of manganese may have deleterious effects on more sensitive subgroups of the population, with sub-threshold neurodegeneration in the basal ganglia, generating a pre-Parkinsonian condition. In the case of zinc, there has as yet been no evidence that it is involved in the etiology of neurodegenerative diseases in humans. Zinc is redox-inactive and, as a result of efficient homeostatic control, does not accumulate in excess. However, adverse symptoms in humans are observed on inhalation of zinc fumes, or accidental ingestion of unusually large amounts of zinc. Also, high concentrations of zinc have been found to kill bacteria, viruses, and cultured cells. Some of the possible mechanisms for cell death are reviewed.

Aluminum↗
PubMed2003

Signification and pain: a semiotic reading of fibromyalgia.

Patients with persistent pain who lack a detectable underlying disease challenge the theories supporting much of biomedical body-mind discourse. In this context, diagnostic labeling is as inherently vulnerable to the same pitfalls of uncertainty that beset any other interpretative endeavour. The end point is often no more than a name rather than the discovered essence of a pre-existent medical condition. In 1990 a Committee of the American College of Rheumatology (ACR) formulated the construct of Fibromyalgia in an attempt to rectify a situation of diagnostic confusion faced by patients presenting with widespread pain. It was proposed that Fibromyalgia existed as a "specific entity", separable from but curiously able to co-exist with any other painful condition. Epistemological and semiotic analyses of Fibromyalgia have failed to find any sign, clinical or linguistic, which could differentiate it from other diffuse musculoskeletal pain states. The construct of Fibromyalgia sought to define a discernable reality outside the play of language and to pass it off as a natural phenomenon. However, because it has failed both clinically and semiotically, the construct also fails the test of medical utility for the subject in persistent pain.

Chronic Disease↗
PubMed2003

A review of the influence of aqueous humor on immunity.

Regulation of immunity within the immune-privileged ocular microenvironment is a dynamic interaction of anatomical features, factors, and cells that work toward suppressing the induction inflammation. Immunosuppressive neuropeptides found in aqueous humor are central to this immunoregulation. These neuropeptides are alpha-melanocyte-stimulating hormone, vasoactive intestinal peptide, calcitonin gene-related peptide, and somatostatin. Along with transforming growth factor-beta2, the neuropeptides target specific cells and pathways in innate and adaptive immunity. These aqueous humor factors prevent pathogen-induced inflammation and activation of Th1 cells, while promoting induction of regulatory T cells. Therefore, the ocular microenvironment, through the constitutive production of immunosuppressive factors found in aqueous humor, maintains immune privilege by manipulating regional innate and adaptive immunity away from inflammatory responses.

Aqueous Humor↗
PubMed2002

New N(3)S donor ligand small peptide analogues of the N-mercaptoacetyl-glycylglycylglycine ligand in the clinically used Tc-99m renal imaging agent: evidence for unusual amide oxygen coordination by two new ligands.

Three new X-ray structurally characterized Re(V)O complexes, ReO(MEG(3)H(2)) (10), ReClO(MAEG(2)H(3)) (11), and [ReO(MECG(2)H(2))](2) (12), were prepared from protected forms of three new ligands, mercaptoethyl-glycylglycylglycine (MEG(3)H(5)), mercaptoacetamide-ethyl-glycylglycine (MAEG(2)H(5)), and mercaptoethyl-carbamoylmethyl-glycylglycine (MECG(2)H(5)). (Subscript on H indicates the number of dissociable protons.) Mercaptoacetyltriglycine (MAG(3)H(5)) is the ligand precursor for the clinically used Tc-99m renal imaging agent. The new potentially N(3)S donor ligands have a glycylglycine carboxyl end as in MAG(3)H(5), but a secondary amine (sp(3) N) replaces one amide (sp(2) N) of MAG(3)H(5). ReO(MEG(3)H(2)) (10) is a typical five-coordinate pseudo-square-pyramidal complex with the oxo ligand at the apex and the trianionic form of MEG(3)H(5) coordinated in the basal plane via N(3)S. In the other complexes, the quadridentate ligand has N(2)OS ligation, with the carbonyl oxygen of the glycyl amide group coordinated trans to the oxo ligand. This unusual ligation mode, which is facilitated by the preferred endo configuration of the ligated glycyl sp(3) N, leaves a vacant basal coordination site. In 11, the chloro ligand completes the equatorial plane, whereas, in 12, a glycine carboxylate oxygen of the ligand on the partner Re completes the equatorial plane. Both complexes thus possess an unexpected pseudo-octahedral geometry. For 10, 11, and 12, the (1)H NMR spectra, monitored from high to low pH, exhibited changes only when the pH was lowered below 6. This finding indicates that at physiological pH these complexes possess the desirable characteristic of existing as one monomeric species having only one ionization state, with the coordinated sp(3) N deprotonated. Below pH 6 and above pH approximately 4, changes in the (1)H NMR shifts indicate that this sp(3) N has become protonated. Thus, the N(3)S ligands in all three complexes exhibit normal coordination above pH approximately 4. However, X-ray data for 11 and 12 and some NMR evidence for 11 indicate that the ligands of the two complexes rearrange at low pH (<3). The striking differences between the solution- and solid-state structures reinforce the caveat that solution structural studies conducted at physiological pH are necessary in order to gain insight into the nature of radiopharmaceuticals.

Crystallography, X-Ray↗
PubMed2002

Assessment of the patency of microvascular venous anastomosis.

There is an absence of data on the timing of occlusion of vessels after anastomosis, and on the possible subsequent reopening (recanalization) of these vessels. This lack of information may be an important factor in the wide discrepancies found among reported patency rates for laboratory microvascular repair. In this study, a total of 300 standard microsurgical anastomoses were performed on rat femoral veins. The patency of each anastomosis was assessed at regular intervals within a 2-week study period. These results showed that the majority of venous occlusions occurred within 1 day after repair. Recanalization of the occluded vein was first seen at day 3 postoperatively. Recanalization was observed over a 2-week postoperative period with increasing frequency. The authors conclude that the optimal time to assess the technical outcome of experimental venous patency is 1 to 2 days after the repair.

Anastomosis, Surgical↗
PubMed2002

NICE and LICE: lessons from a health district. National Institute for Clinical Excellence. Local institutes of clinical excellence.

This paper describes experiences of implementing guidance from the National Institute for Clinical Excellence (NICE) in the East Riding and Hull Health Authority area. Attempts have been made to integrate NICE guidance with the decision-making, service planning and monitoring processes but overall progress has been limited. Contributory reasons are explored, along with suggestions on how to ensure that NICE can help ensure effective and equitable services.

Academies and Institutes↗
PubMed2002

Transureteroureterostomy obstruction mimicking acute tubular necrosis.

A patient receiving nephrotoxic chemotherapy for metastatic cervical cancer was examined for acute renal failure. A Tc-99m MAG3 scan showed symmetric function, bilateral increasing parenchymal activity, and no tracer excretion in either collecting system. The differential diagnosis included cisplatin-induced nephrotoxicity, dose infiltration, and obstruction of the common ureter. Analysis of the scan, an image over the injection site, and a delayed image of the urinary tract indicated obstruction of the common ureter at the anastomotic site of the transureteroureterostomy. In patients with a transureteroureterostomy, symmetric renal dysfunction, and no bladder activity, a delayed image of the urinary tract should be obtained to distinguish obstruction from acute tubular necrosis.

Acute Kidney Injury↗
PubMed2002

Comparison of procedures for evaluating laboratory performance in external quality assessment schemes for lead in blood and aluminum in serum demonstrates the need for common quality specifications.

BACKGROUND: The different scoring methods used by eight European External Quality Assessment Schemes (EQASs) for occupational and environmental laboratory medicine were compared to develop suitable quality specifications as a step toward harmonization. METHODS: Real results for blood lead and serum aluminum assays, reported by participants in Italian and United Kingdom EQASs, were evaluated according to individual scheme scoring criteria. The same results were then used to produce z scores using scheme-based between-laboratory SDs as the estimate of variability to determine whether simple performance-derived quality specifications produced better agreement among schemes. RESULTS: The schemes gave conflicting assessments of participants' performance, and participants judged to be successful by one scheme could be defined as performing inadequately by another. An approach proposed by Kenny et al. (Scand J Clin Lab Invest 1999;59:585), which uses clinical inputs to set targets for analytical imprecision, bias, and total error allowable, was then used to elaborate quality specifications. CONCLUSIONS: We suggest that the CLIA '88 recommendations for blood lead (+/- 40 micro g/L or +/- 10% of the target concentration, whichever is the greater) could be used as a quality specification, although a revision to +/- 30 micro g/L or +/- 10% is recommended. For serum aluminum, a suitable quality specification of +/- 5 micro g/L or +/- 20% of the target concentration, whichever is the greater, is suggested. These specifications may be used to compare laboratory performance across schemes.

Aluminum↗
PubMed1999

Re(V)=O(N(2)S(2)) Complexes with N(2)S(2) = Thio-Amido-Secondary Amine-Thio Chelate Ligands: Synthesis, Structure, and Characterization of Solution Forms.

Anti- and syn-ReO(L-cysteine-acetyl-cysteamine) (1 and 2, respectively), and the dimethyl derivatives anti- and syn-ReO(L-penicillamine-acetyl-cysteamine) (3 and 4, respectively), were synthesized. Anti and syn refer to the relationship of the oxo ligand and carboxyl group of the cysteine/penicillamine residue. In the structures of 1 and 4, determined by X-ray diffraction, the oxo/carboxyl relationship was anti in 1 and syn in 4. Such thio-amido-amine-thio (MAMA for monoamido monoamine) type complexes are being investigated as radiopharmaceuticals. The charge and the number of species present under physiological conditions influence biodistribution, and understanding factors influencing the pK(a) of the coordinated secondary amine is essential for successful design of such agents. Dissociation of the proton on the secondary amine alters the charge and structure. For both 1 and 2, the (1)H NMR spectra, monitored as a function of pH, exhibited changes in two pH regions: near pH 4 the signals (especially the H(alpha) of the cysteine residue) shifted, and from pH approximately 6-8 the signals shifted again and broadened. These shift changes are consistent with dissociation of the carboxyl proton to give a monoanion I, and of the amine proton to give a dianion II, respectively. The cysteamine chelate ring of 1 and 4, anchored by the amine donor, is highly puckered in the solid state. Torsion angles, calculated from (1)H NMR (3)J values at pH 3, 5 and 8, indicate that in solution the cysteamine chelate ring is also highly puckered in the neutral form and I, but relatively planar in II. Since five-membered chelate rings are more planar when an anchoring amine is deprotonated, the data are consistent with II being an NH-deprotonated form rather than an OH(-) axially ligated form. The high acidity of the amine in 1 and 2 compared to analogues with two amine donors indicates that the amido group is a modest donor. The signal broadening observed as I and II interconvert, an unusual effect for NH/N(-) exchange, is due primarily to the low rate of exchange at the OH(-) concentration needed to convert I to II. Making the metal (Re/Tc) more electron rich may decrease the acidity of the NH, but since the NH in 1 and 2 is particularly acidic, this approach is unlikely to work. Our results suggest that introduction of an electron-withdrawing group into the ligand may lower the NH pK(a) of the complex below the physiologically relevant range and give a species with a well-defined charge.

Journal Article↗
PubMed1998

Elimination of an Infestation of Rat Fur Mites (Radfordia ensifera) from a Colony of Long Evans Rats, Using the Micro-dot Technique for Topical Administration of 1% Ivermectin.

Micro-dot delivery of 1% ivermectin was used in an effort to eliminate an infestation of rat fur mites (Radfordia ensifera) from a conventionally housed colony of Long Evans rats. The colony was used for breeding as well as for behavioral testing. A micropipette was used to apply a 1% solution of ivermectin (2 mg/kg of body weight) to the skin on the dorsal aspect of the shoulder. Three treatments were applied at approximately 2-week intervals. All rats in the colony were treated. However, to avoid toxicity to neonates, nursing females and their pups (control group) received mineral oil in lieu of ivermectin until after weaning, at which time they also were treated with ivermectin. During the treatment phase, skin scrapings were used to detect mites. Control rats remained positive for fur mites when treated with mineral oil. After 3 applications of ivermectin, all rats were found to be free of mites. During the posttreatment phase, skin scrapings, dorsal tape tests, and a washing method were performed on euthanatized rats to detect mites. Rats tested up to 129 days (18 weeks) after ivermectin treatment were still free of mites. In a breeding colony composed of rats of various sizes and ages, micropipette delivery of ivermectin allowed for accurate dosing to eliminate fur mites, while preventing inadvertent toxicosis. We did not detect obvious adverse effects on the breeding program or on the behavioral studies in which these rats were subsequently used, nor did we detect morbidity or mortality associated with ivermectin administration.

Journal Article↗
PubMed1996

Synthesis and Characterization of Rhenium(V) Oxo Complexes with a New Thiol-Amide-Thiourea Ligand System. X-ray Crystal Structure of [1-Phenyl-3-[2-((2-thioacetyl)amino)ethyl]thioureato]oxorhenium(V).

General methods for preparing Re(V)O complexes with a novel series of thiol-amide-thiourea (TATU) ligands, a new class of N(2)S(2) chelates, were developed. The TATU ligands, the first multidentate systems designed with a bidentate thiourea moiety, have been used to prepare the first high-valent transition metal complexes with bidentate thiourea coordination. Direct reaction of N-(2-aminoethyl)-2-((triphenylmethyl)thio)acetamide (1) with phenyl, 4-methoxyphenyl, 4-chlorophenyl, and methyl isothiocyanate afforded ready access to the corresponding S-protected TATU ligands in one step. A two-step preparation of the N,N-dimethylthiourea TATU ligand derived from 1 was also developed. Deprotection of thiols in trifluoroacetic acid with triethylsilane followed by a ligand exchange reaction with Re(V)O precursors yielded neutral ReO(TATU) complexes. The structure of [1-phenyl-3-[2-((2-thioacetyl)amino)ethyl]thioureato]oxorhenium(V) (6a) was determined by X-ray diffraction methods. Crystal data for 6a: C(11)H(12)N(3)O(2)ReS(2), fw 468.6, orthorhombic, Pca2(1); a = 22.605(5) Å, b = 13.029(3) Å, c= 9.698(2) Å; V = 2856.3(11) Å(3); Z = 8. The coordination environment of 6a was pseudo-square-pyramidal with a deprotonated thiol S, deprotonated amide N, deprotonated thiourea N, and thiocarbonyl S coordinated in the basal plane and the oxo ligand in the apical position. The thiourea function forms a four-membered chelate ring in the multidentate TATU ligands. The two N-C and the S-C bond distances within the monodeprotonated thiourea moiety were typical of bonds with multiple-bond character. Solution (1)H NMR data for all five complexes were consistent with the solid-state structure of 6a. A broad singlet attributable to the uncoordinated NH group of thiourea was observed for the monosubstituted thiourea complexes but was not present for the N,N-dimethylthiourea derivative. Instead, two singlets of equal intensity were observed for the two methyl groups, indicating that there is restricted rotation around the C-N(CH(3))(2) bond and an extended pi system in the thiourea moiety. The four-membered ring might cause difficulty because the M-S distance would be relatively long in an undistorted ligand. This may be the reason such chelate ligands have not been previously investigated. However, the N-C-S angle narrows to approximately 105 degrees, permitting a Re-S bond with a typical bond length to be formed. We conclude that such a ring represents a versatile new building block to create multidentate ligands.

Journal Article↗
PubMed1996

Rhenium(V) Oxo Complexes of Novel N(2)S(2) Dithiourea (DTU) Chelate Ligands: Synthesis and Structural Characterization.

The compounds RNHC(=S)NH(CH(2))(n)()NHC(=S)NHR were prepared in a search for new, relatively small N(2)S(2) ligands. These dithiourea (DTU) ligands are the first chelates containing two potentially bidentate thiourea moieties. A one-step reaction of 1,3-diaminopropane (1) with aryl or alkyl isothiocyanates or of 1,2-diaminoethane (2) with phenyl isothiocyanate afforded the target ligands in excellent yields (95-98%). The Re(V)=O complexes of RNHC(=S)NH(CH(2))(3)NHC(=S)NHR ligands were obtained through ligand exchange reactions with Re(V) precursors. The chemistry required neither protection of the sulfur atoms for ligand synthesis nor deprotection prior to metal complexation. The structure of (1-phenyl-3-(3-phenylthioureido)propyl]thioureato)oxorhenium(V) (7a), determined by X-ray diffraction methods, revealed the expected pseudo-square-pyramidal geometry with an N(2)S(2) basal and an apical oxo donor set. Both coordinated N's (N(c)) were deprotonated. One uncoordinated N (N(u)) was deprotonated, producing a neutral complex containing an unexpected new type of dianionic, four-membered N,S chelate. In the crystal, the N(u) atoms, N(3)H and N(4), of one complex each formed an H-bond with N(4) and N(3)H, respectively, of a symmetry-related complex. The N(c)-C-S bond angles (106.1(6) and 101.5(6) degrees ) were severely distorted from the 120 degrees expected for an sp(2)-hybridized C. However, these small bite angles and the large N-Re-N bond angle (86.1(3) degrees ) allowed for the formation of two four-membered chelate rings with normal Re-N and Re-S bond distances. Attempts to prepare complexes with the PhNHC(=S)NH(CH(2))(2)NHC(=S)NHPh ligand were unsuccessful. These results suggest that a central five-membered chelate ring is too small to accommodate bidentate coordination of both thiourea moieties. NMR studies in methanol established that the neutral complex with one uncoordinated N deprotonated was the favored form in neutral and basic solutions. However, under acidic conditions, a cationic form with both uncoordinated N's protonated was favored.

Journal Article↗