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Biomedical subjects

S M Lawrence

Publications and source records attributed to S M Lawrence.

13 recordsLinked to original sources
PubMed2006

Retrospective data for diabetic foot complications: only the tip of the iceberg?

Admission rates for diabetes-related foot complications to an Australian hospital were assessed by comparing the frequently used method of retrospectively identifying patients according to International Classification of Diseases (ICD) codes with that of prospectively identifying patients at the time of admission. The aim was to determine the true admission rate of diabetes-related foot complications and to assess the ability of ICD discharge codes to accurately represent the clinical severity of each identified admission. The retrospective study of ICD codes identified approximately one-third of the patients admitted during the prospective studies. Furthermore, ICD codes allocated in the prospective studies failed to accurately represent the clinical condition in 61% of cases and the corresponding Weighted Inlier Equivalent Separations weighting resulted in a $215,000/year deficit for admissions to a single hospital.

Adult↗
PubMed2005

Creation of a multidisciplinary, evidence based, clinical guideline for the assessment, investigation and management of acute diabetes related foot complications.

AIMS: To design a multidisciplinary, evidenced-based, clinical guideline for the assessment, investigation and management of inpatients with acute diabetes related foot complications. METHODS: A systematic search of both published (identified by searching all major electronic databases and hand searching key journals) and unpublished literature (derived from national and internationally recognized experts) identified 266 articles specific to diabetes related foot complications. Of these, 126 (47%) were assessed to be methodologically sound and clinically relevant. A narrative summary with the articles tabulated according to their level of evidence was prepared. A multidisciplinary expert group of health professionals, with a known interest and recognized expertise in diabetes related foot complications, was established to assess the evidence. RESULTS: The multidisciplinary expert group used the identified literature and clinical experience to create a comprehensive, evidence-based, clinical guideline for the assessment, investigation and management of acute diabetes related foot complications. Included within the guideline is a novel, diabetes specific classification system, which codes for the presence/absence and severity of the four principle causative factors (Neuropathy, Vascular compromise, Ulceration and Infection) in the development of acute diabetes related foot complications. CONCLUSION: Through the creation and implementation of this evidence-based clinical guideline, specific for acute diabetes related foot complications, it is hoped that health professionals will be better equipped to make informed decisions for this patient population. This may benefit the individual and health system through reductions in amputation rate, length of hospital stay and health expenditure.

Decision Making↗
PubMed2004

Assessment and management of inpatients with acute diabetes-related foot complications: room for improvement.

BACKGROUND: Australian data are currently lacking regarding management guidance, resource usage and outcomes of patients with diabetes requiring hospitalization for management of acute foot complications. AIMS: The aims of the present study were to review hospital admissions for diabetes-related foot complications and current assessment and management of these complications, and to formulate recommendations for future models of care. METHODS: A retrospective review of patient records from 1 July 1999 to 30 June 2000 was carried out. Recorded assessment, investigations, management, amputation rates, referral rates and length of hospital stay were reviewed. RESULTS: There were 69 admission episodes in 12 months (total patients n = 50). The mean age was 64 years, with 44 male patients (64%) and 25 female patients (36%). The mean diabetes duration was 11 years (range <1-47 years). The majority of patients had type 2 diabetes. Assessment for known risk factors for ulceration and amputation was variable with history of previous ulcer/amputation recorded for 24 (35%) admissions, results of neurological assessment recorded for 11 (16%) and assessment of pedal pulses documented for 51 (74%). Glycated haemoglobin was performed during 35 (51%) admissions. Patients were admitted under one of 11 different inpatient units and the average interdepartmental referral rate was one referral per patient per admission. The average length of stay was 17 days, with total bed days occupied 1163 days. Minor amputation was performed in 25 (36%) cases and major amputation in 8 (11%). CONCLUSIONS: Clinical assessment, investigation and management of this population are highly variable. This has a significant impact on the final clinical outcome, and changes to current processes are required to overcome the substantial burden of diabetic foot disease.

Amputation, Surgical↗
PubMed2001

Determination of nucleotides and sugar nucleotides involved in protein glycosylation by high-performance anion-exchange chromatography: sugar nucleotide contents in cultured insect cells and mammalian cells.

We have developed a simple and highly sensitive HPLC method for determination of cellular levels of sugar nucleotides and related nucleotides in cultured cells. Separation of 9 sugar nucleotides (CMP-Neu5Ac, CMP-Neu5Gc, CMP-KDN, UDP-Gal, UDP-Glc, UDP-GalNAc, UDP-GlcNAc, GDP-Fuc, GDP-Man) and 12 nucleotides (AMP, ADP, ATP, CMP, CDP, CTP, GMP, GDP, GTP, UMP, UDP, and UTP) was examined by reversed-phase HPLC and high-performance anion-exchange chromatography (HPAEC). Although the reversed-phase HPLC, using an ion-pairing reagent, gave a good separation of the 12 nucleotides, it did not separate sufficiently the sugar nucleotides for quantification. On the other hand, the HPAEC method gave an excellent and reproducible separation of all nucleotides and sugar nucleotides with high sensitivity and reproducibility. We applied the HPAEC method to determine the intracellular sugar nucleotide levels of cultured Spodoptera frugiperda (Sf9) and Trichoplusia ni (High Five, BTN-TN-5B1-4) insect cells, and compared them with those in Chinese hamster ovary (CHO-K1) cells. Sf9 and High Five cells showed concentrations of UDP-GlcNAc, UDP-Gal, UDP-Glc, GDP-Fuc, and GDP-Man equal to or higher than those in CHO cells. CMP-Neu5Ac was detected in CHO cells, but it was not detected in Sf9 and High Five cells. In conclusion, the newly developed HPAEC method could provide valuable information necessary for generating sialylated complex-type N-glycans in insect or other cells, either native or genetically manipulated.

Animals↗
PubMed2001

Cloning and expression of human sialic acid pathway genes to generate CMP-sialic acids in insect cells.

The addition of sialic acid residues to glycoproteins can affect important protein properties including biological activity and in vivo circulatory half-life. For sialylation to occur, the donor sugar nucleotide cytidine monophospho-sialic acid (CMP-SA) must be generated and enzymatically transferred to an acceptor oligosaccharide. However, examination of insect cells grown in serum-free medium revealed negligible native levels of the most common sialic acid nucleotide, CMP-N-acetylneuraminic acid (CMP-Neu5Ac). To increase substrate levels, the enzymes of the metabolic pathway for CMP-SA synthesis have been engineered into insect cells using the baculovirus expression system. In this study, a human CMP-sialic acid synthase cDNA was identified and found to encode a protein with 94% identity to the murine homologue. The human CMP-sialic acid synthase (Cmp-Sas) is ubiquitously expressed in human cells from multiple tissues. When expressed in insect cells using the baculovirus vector, the encoded protein is functional and localizes to the nucleus as in mammalian cells. In addition, co-expression of Cmp-Sas with the recently cloned sialic acid phosphate synthase with N-acetylmannosamine feeding yields intracellular CMP-Neu5Ac levels 30 times higher than those observed in unsupplemented CHO cells. The absence of any one of these three components abolishes CMP-Neu5Ac production in vivo. However, when N-acetylmannosamine feeding is omitted, the sugar nucleotide form of deaminated Neu5Ac, CMP-2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (CMP-KDN), is produced instead, indicating that alternative sialic acid glycoforms may eventually be possible in insect cells. The human CMP-SAS enzyme is also capable of CMP-N-glycolylneuraminic acid (CMP-Neu5Gc) synthesis when provided with the proper substrate. Engineering the CMP-SA metabolic pathway may be beneficial in various cell lines in which CMP-Neu5Ac production limits sialylation of glycoproteins or other glycans.

Amino Acid Sequence↗
PubMed2001

Effect of initial joint position on nerve-cuff recordings of muscle afferents in rabbits.

The objective was to characterize nerve-cuff recordings of muscle afferents to joint rotation over a large part of the physiological joint range. This information is needed to develop control strategies for functional electrical stimulation (FES) systems using muscle afferent signals for sensory feedback. Five acute rabbit experiments were performed. Tripolar cuff electrodes were implanted around the tibial and peroneal divisions of the sciatic nerve in the rabbit's left leg. The electroneurograms (ENG) were recorded during passive ankle rotation, using a ramp-and-hold profile starting at seven different joint positions (excursion = 5 degrees, velocity = 10 degrees/s, initial positions 60 degrees, 70 degrees, 80 degrees, 90 degrees, 100%, 110 , and 120 ). The amplitude of the afferent activity was dependent on the initial joint position. The steady-state sensitivity of both nerve responses increased with increasing joint flexion, whereas the dynamic sensitivity increased initially but then decreased. The results indicate that recordings of the muscle afferents may provide reliable information over only a part of the physiological joint range. Despite this limitation, muscle afferent activity may be useful for motion feedback if the movement to be controlled is within a narrow joint range such as postural sway.

Afferent Pathways↗
PubMed2000

Cloning and expression of the human N-acetylneuraminic acid phosphate synthase gene with 2-keto-3-deoxy-D-glycero- D-galacto-nononic acid biosynthetic ability.

Sialic acids participate in many important biological recognition events, yet eukaryotic sialic acid biosynthetic genes are not well characterized. In this study, we have identified a novel human gene based on homology to the Escherichia coli sialic acid synthase gene (neuB). The human gene is ubiquitously expressed and encodes a 40-kDa enzyme. The gene partially restores sialic acid synthase activity in a neuB-negative mutant of E. coli and results in N-acetylneuraminic acid (Neu5Ac) and 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN) production in insect cells upon recombinant baculovirus infection. In vitro the human enzyme uses N-acetylmannosamine 6-phosphate and mannose 6-phosphate as substrates to generate phosphorylated forms of Neu5Ac and KDN, respectively, but exhibits much higher activity toward the Neu5Ac phosphate product.

Amino Acid Sequence↗
PubMed1997

Aggregation and surface properties of synthetic double-chain non-ionic surfactants in aqueous solution.

Double-chain non-ionic surfactants have been synthesized with the general formula 2CnMPEG750, where n is the number of carbons in the alkyl chains and 750 is the molecular weight of the monomethoxypolyoxyethylene (MPEG) head group. The aggregation and surface properties in dilute aqueous solution (< 1.0% w/w) of surfactants with n = 8, 10 and 12 have been determined. Each of the surfactants formed clear, foaming, non-birefringent solutions. Total-intensity light scattering indicated the presence of micelles with aggregation numbers of 36, 68 and 74 for the 2C8, 2C10 and 2C12 surfactants, respectively, whereas photon-correlation studies yielded radii, assuming spherical aggregates, of 59-103 A. Surface-tension measurements gave critical micelle concentrations for the surfactants in the range 1.15-7.24 x 10(-6) M; these, as expected, decreased when the number of carbon atoms in the alkyl chains was increased. Such studies are important in the design of new surfactants as vehicles for drug delivery because it is imperative to be able to predict the type of aggregate formed by a surfactant.

Light↗
PubMed1993

Liposomal (MLV) polymyxin B: physicochemical characterization and effect of surface charge and drug association.

Neutral and charged large vortexed multilamellar hydrogenated egg phosphatidylcholine liposomes containing the polycationic antibiotic polymyxin B (PXB) were characterized with respect to lipid-drug interactions (differential scanning calorimetry), surface charge (zeta potential analysis), size (photon correlation spectroscopy) and morphology (transmission electron microscopy). These physicochemical results will be used to develop a liposomal drug delivery system for PXB that may be useful in the clinical treatment of lung infection in cystic fibrosis patients. The liposomal morphology and membrane integrity of all the preparations were unaffected by associated antibiotic. Drug encapsulation increased in the order neutral = positive < negative, the negatively charged liposomes increasing drug association 2-fold. The phase transition temperature of neutral and positive liposomes was not significantly affected by PXB. Drug-loaded negative liposomes showed a decreased phase transition possibly due to attractive electrostatic interactions between drug and lipid that tended to increase drug penetration and destabilize the liposome bilayer. Drug loading did not affect liposome size. However, both empty and loaded negative liposomes were significantly smaller (approx. 1 micron) than neutral and positive (approx. 2.5 microns) liposomes. Increased encapsulation with negative liposomes is therefore due not to an increase in the entrapped volume but to electrostatic interactions.

Calorimetry, Differential Scanning↗
PubMed1991

VESICA: computer graphics modeling of lipid vesicles.

A vesicle simulation and computer analysis program, VESICA, is described which employs spherical projections of triangularly tessellated icosahedra to produce molecular graphics models of the three-dimensional structures of lipid vesicles. The program is used to analyze the molecular architecture of small unilamellar vesicles of dipalmitoyl-phosphatidylcholine and is demonstrated as a worthwhile investigative tool for determining the factors that govern the minimum vesicle size.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1981

High performance liquid chromatography (HPLC) of natural products. IV. The use of HPLC in biosynthetic studies of cephalosporin C in the cell-free system.

A new cepham metabolite has been isolated from the filtered broth of Cephalosporium acremonium by high performance liquid chromatography (HPLC) and identified as 7 beta-(5-D-amino-adipamido)-3 beta-hydroxy-3 alpha-methyl-cepham-4 alpha-carboxylic acid (I). Pure penicillin N was prepared using HPLC in the analytical mode. When I was added in place of penicillin N as substrate for the cell-free biosynthetic of cephalosporin, no formation of deacetoxycephalosporin C (II) was observed. A synthetic cepham derivative, 7 beta-(5-D-aminoadipamido)-3-exomethylene-cepham-4 alpha-carboxylic acid (III) was also tested in the cell-free system as a possible intermediate. The compound III was shown to be an inhibitor of the ring expansion enzyme that converts penicillin N to deacetoxycephalosporin C.

Acremonium↗
PubMedDate not supplied

Parental attitudes toward behavior management techniques used in pediatric dentistry.

Previous studies evaluating parents' attitudes toward behavior management techniques used in pediatric dentistry suggest that parental attitudes are generally negative. The purpose of this study was to reexamine this issue by comparing the effect of prior explanation on parental acceptance of eight behavior management techniques. Videotaped segments were made of children's dental appointments containing examples of eight behavior management techniques. One group of 40 parents viewed a videotape which provided no explanation for each technique before it was shown. Another group of 40 parents viewed a videotape which provided no explanation of the techniques. The parents then were asked to rate the acceptability of each technique using a visual analogue scale. Results indicated that the informed parents were significantly more accepting of behavior management techniques than the uninformed parents but both groups were generally positive about the techniques studied. Further, parents reporting greater stress were less accepting of the techniques studied.

Adult↗