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Biomedical subjects

D Mulholland

Publications and source records attributed to D Mulholland.

12 recordsLinked to original sources
PubMed2004

Management of endophthalmitis with retained intraocular foreign body.

AIMS: To assess the impact of primary injection of intravitreal antibiotics and delayed pars plana vitrectomy with removal of intraocular foreign body (IOFB) in patients with clinical features of bacterial endophthalmitis and retained IOFB. METHODS: Retrospective review of all patients with clinical features of infective endophthalmitis and a retained IOFB who had immediate injection of intravitreal antibiotics and delayed pars plana vitrectomy with removal of IOFB in two vitreo-retinal centres during 1995-2001. Nine patients were identified and minimum follow-up was 3 months. RESULTS: Four of the nine patients had a final visual outcome of 6/18 or better. One patient developed total retinal detachment. CONCLUSIONS: The current series suggests that immediate injection of intravitreal antibiotics with delayed removal of IOFB in eyes with clinical features of infective endophthalmitis and a retained IOFB is a possible alternative to immediate removal of IOFB. This management may be associated with preservation of the eye and restoration of useful visual acuity.

Adult↗
PubMed2001

Expedient asymmetric synthesis of all four isomers of N,N'-protected 2,3-diaminobutanoic acid.

2,3-Diaminobutanoic acid (DAB) is found in several peptide antibiotics, toxins, and biologically active molecules. This paper describes the practical and highly enantioselective synthesis of all four N,N'-protected DAB stereoisomers using an asymmetric Rh(I)-phosphine-catalyzed hydrogenation of isomeric enamides as the key step. Thermal and photochemical isomerization of the enamide hydrogenation substrates coupled with catalyst-geometric isomer pairing allows targeted synthesis of single DAB isomers in maximum yield.

Journal Article↗
PubMed2000

Type VIII collagen stimulates smooth muscle cell migration and matrix metalloproteinase synthesis after arterial injury.

Type VIII collagen is a matrix protein expressed in a number of tissues undergoing active remodeling, including injured arteries during neointimal formation and in human atherosclerotic plaques; however, very little is known about its function. We have investigated whether the type VIII collagen stimulates smooth muscle cell (SMC) migration and invasion by binding to integrin receptors and up-regulating matrix metalloproteinase (MMP) production. SMCs attached to plates coated with type VIII collagen in a dose-dependent manner, with maximal attachment occurring with coating solutions containing 25 microgram/ml collagen. Type VIII collagen at 100 microgram/ml stimulated an 83-fold increase in the migration of SMCs in a chemotaxis chamber. Antibodies against beta1 integrin receptors prevented attachment and migration of SMCs. Antibodies against alpha1 or alpha2 integrins reduced attachment of SMCs to type VIII collagen by 29% and 77%, respectively. We found that SMCs grown from the rat neointima, but not medial SMCs, increased their production of MMP-2 and -9 on adherence to type VIII collagen. This suggests that there is an important difference in phenotype between intimal and medial SMCs and that intimal SMCs have distinct matrix-dependent signaling mechanisms. Our findings suggest that type VIII collagen deposited in vascular lesions functions to promote SMC attachment and chemotaxis, and signals through integrin receptors to stimulate MMP synthesis, all of which are important mechanisms used in cell migration and invasion.

Animals↗
PubMed2000

Smooth muscle cell matrix metalloproteinase production is stimulated via alpha(v)beta(3) integrin.

This study tests the hypothesis that alpha(v)beta(3) integrin receptors play a critical role in smooth muscle cell (SMC) migration after arterial injury and facilitate migration through the upregulation of matrix metalloproteinase (MMP) activity. We showed that beta(3) integrin mRNA was upregulated by SMCs in the balloon-injured rat carotid artery in coincidence with MMP-1 expression and early SMC migration. Treatment with the beta(3) integrin-blocking antibody F11 significantly decreased SMC migration into the intima at 4 days after injury, from 110.8+/-30.8 cells/mm(2) in control rats to 10.29+/-7.03 cells/mm(2) in F11-treated rats (P=0.008). By contrast, there was no effect on medial SMC proliferation or on medial SMC number in the carotid artery at 4 days. In vitro, we found that human newborn SMCs produced MMP-1 but that adult SMCs did not. This was possibly due to the fact that newborn SMCs expressed alpha(v)beta(3) integrin receptors, whereas adult SMCs did not. Stimulation of newborn (alpha(v)beta(3)+) SMCs with osteopontin, a matrix ligand for alpha(v)beta(3), increased MMP-1 production from 114.4+/-35.8 ng/mL at 0 nmol/L osteopontin to 232.5+/-57.5 ng/mL at 100 nmol/L osteopontin. Finally, we showed that stimulation of newborn SMCs with platelet-derived growth factor-BB and osteopontin together increased the SMC production of MMP-9. Thus, our results support the hypothesis that SMC alpha(v)beta(3) integrin receptors play an important role in regulating migration by stimulating SMC MMP production.

Animals↗
PubMed2000

Unique and multifunctional adhesion junctions in the testis: ectoplasmic specializations.

In this paper, we review the structure and function of a unique type of actin-related intercellular adhesion junctions in the testis. Based on their ultrastructure, the junctions are divided into five distinct domains. The currently identified molecular components of each domain are summarized. In addition, the architecture of the mammalian system is compared with that of non-mammalian vertebrates. Functionally, the junctions are related to the turnover of adhesion between Sertoli cells, to the attachment of spermatids to the seminiferous epithelium, and to sperm release. They also are part of the mechanism by which spermatids are moved through the epithelium. Evidence consistent with adhesion and motility related functions is discussed. Control, both of junction turnover and of microtubule-based transport, is identified as an important avenue for future research.

Actins↗
PubMed1992

Extradural clonidine infusions for analgesia after total hip replacement.

We have examined the effectiveness of extradural clonidine infusions for postoperative analgesia and the effect of clonidine on extradural morphine. In a double-blind, controlled study, patients, undergoing total hip replacement were allocated randomly to receive one of two doses of extradural clonidine (25 micrograms h-1 or 50 micrograms h-1), low dose extradural morphine or a combination of morphine and clonidine. Pain scores in the morphine group were significantly greater than in the clonidine groups (P less than 0.01) and the combination group (P less than 0.05) during the first 1 h after surgery. The requirements for systemic analgesia were least in the combination and larger dose clonidine group, and the duration of effect of the initial bolus dose was significantly longer compared with the morphine and low dose clonidine groups (P less than 0.05). Arterial pressure was reduced in the clonidine groups, although the incidence of clinical hypotension was low. There were no significant differences between the groups in emetic symptoms or urinary retention.

Adult↗
PubMed1991

The role of the teaching hospital. A survey of paediatric anaesthetic techniques used by trainee anaesthetists on a regional training scheme.

All trainee anaesthetists on the Northern Ireland training scheme were surveyed about the techniques they use when anaesthetising elective paediatric cases. We compared the practice of doctors with specialist paediatric training to that of others and discovered that trainees with specialist training were more likely (p less than 0.05) to admit parents during induction, but were less likely (p less than 0.05) to visit their patients pre-operatively and routinely to use suxamethonium. Other general findings were confusion over the re-use of halothane and extensive involvement of trainee anaesthetists in neonatal resuscitation.

Adolescent↗
PubMed1991

Intubation with propofol augmented with intravenous lignocaine.

Sixty patients of ASA grade 1 and aged 18 to 55 years were admitted to a double-blind study. Anaesthesia was induced with propofol 2.5 mg/kg after intravenous pretreatment with lignocaine 1.5 mg/kg or a similar volume of isotonic saline. The quality of subsequent tracheal intubation was graded and the pressor response to tracheal intubation assessed. There were no significant differences between treatment groups.

Adolescent↗
PubMed1990

Mixtures of semisynthetic species of cerebroside sulfate with dipalmitoyl phosphatidylcholine. Thermotropic phase behavior and permeability.

The phase behavior of mixtures of dipalmitoyl phosphatidylcholine (DPPC) with semisynthetic species of cerebroside sulfate (CBS) containing palmitic acid (C16:0-CBS) or lignoceric acid (C24:0-CBS) in 0.1 M KCl was studied using differential scanning calorimetry. DPPC and C16:0-CBS were miscible in all proportions in the gel phase above 10 mol% CBS and in the liquid-crystalline phase. However, C24:0-CBS was less miscible with DPPC over a wide concentration range in the gel phase. At high CBS concentrations it was probably also not entirely miscible with DPPC in the liquid-crystalline phase. Small amounts of both species of CBS lowered the transition temperature and enthalpy of DPPC, suggesting that they are more soluble in the liquid-crystalline phase of DPPC than the gel phase. The transition temperature at higher CBS concentrations was also less than expected, especially after cycling through the phase transition in the case of C24:0-CBS, suggesting that mixing with DPPC inhibited the intermolecular hydrogen bonding interactions and dehydration of CBS. In C24:0-CBS-DPPC mixtures several populations were present over a wide compositional range, including two solid-solid solutions of fixed composition. At high C24:0-CBS concentrations some C24:0-CBS also phase separated out of the mixture. Structural considerations suggested that the C24:0-CBS which is mixed with DPPC must be interdigitated into the DPPC bilayer. Other populations that are present may have a different structural organization. A fatty acid spin label in these mixtures was a little less ordered than in either lipid by itself. The permeability of these lipids, as well as the two asymmetric species 1-stearoyl-2-caproyl phosphatidylcholine and 1-stearoyl-2-myristoyl phosphatidylcholine (18:10PC and 18:14PC), to a water-soluble spin label tempocholine chloride was also measured. The studies with 18:10PC and 18:14PC indicated that both triple-chain mixed interdigitated bilayers and double-chain partially interdigitated bilayers can trap water-soluble substances and have low permeability. Both species of CBS could also entrap the spin label and had low permeability at 4 degrees C. However, they rapidly lost the entrapped compound when they transformed into their stable dehydrated phases or into the liquid-crystalline phase. Mixing with DPPC prevented both of these losses. These studies supported the conclusion that a significant amount of the CBS was mixed with the DPPC and that this mixing prevented the dehydration changes which CBS undergoes by itself.(ABSTRACT TRUNCATED AT 400 WORDS)

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1967

Alberta northern field work, 1966: rheumatic heart disease in LaCrete and Paddle Prairie.

A sociologic and medical study was undertaken of the incidence of rheumatic heart disease in an isolated Mennonite colony in Northern Alberta, Canada. A group of Métis in a nearby settlement was used as a control. A total of 1294 individuals were examined, and evidence of carditis was found in 42 Mennonites.This project is one of a series of student summer research programs sponsored by the Department of Community Medicine, University of Alberta, and supported by grants from the Provincial Department of Health during the past three summers.The students - medical and dental - receive in Edmonton a seven- to 10-day orientation and indoctrination course dealing with the sociological, anthropological and medical problems likely to be met with in the North. Research protocol and methodological techniques are prepared and devised with student participation. A minimum of supervision is given in the field to encourage the undergraduates to adapt and adjust to a changed environment. Student response to this type of learning experience has been most encouraging.

Alberta↗