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Biomedical subjects

E Scott

Publications and source records attributed to E Scott.

At least 19 recordsLinked to original sources
PubMed2006

A phase I study of intravenous TZT-1027 administered on day 1 and day 8 of a three-weekly cycle in combination with carboplatin given on day 1 alone in patients with advanced solid tumours.

BACKGROUND: TZT-1027 is a tubulin-binding drug and synthetic derivative of dolastatin-10 with cytotoxic and antivascular activity in vitro and in vivo. Studies have demonstrated anti-tumour activity in several tumour types. METHODS: Patients were treated with escalating doses of TZT-1027 and carboplatin at doses from 1.6 to 2.0 mg/m2 and AUC 4 and 5 respectively. For pharmacokinetic analysis, plasma sampling was done during the first course using a high-performance liquid chromatographic assay. RESULTS: 14 patients received a total of 55 cycles at three dose levels. Dose limiting toxicities (DLTs) were first observed with 1.6 mg/m2 TZT-1027 and carboplatin AUC 5; 1 patient had grade 4 neutropenia and a delay in day 8 treatment occurred in two patients (gr 2 fatigue, gr 3 diarrhoea). At TZT-1027 2 mg/m2 and carboplatin AUC 5, one patient experienced grade 3 paralytic ileus. The most frequent toxicities were neutropenia, anaemia, fatigue, constipation, infection and vomiting. Peripheral neuropathy was reported in 36% of patients. One patient (pancreatic adenocarcinoma) achieved a partial response lasting 181 days. Pharmacokinetic analysis did not demonstrate any interaction between TZT-1027 and carboplatin. CONCLUSIONS: The recommended phase II dose is TZT-1027 1.6 mg/m2 and carboplatin AUC 5. No evidence of a PK interaction between these agents was observed.

Adult↗
PubMed2005

Estimating the cost of hospital services in a small island state: a case study of the Milton Cato Memorial Hospital in St Vincent and the Grenadines.

Cost estimates are derived for services provided at the Milton Cato Memorial Hospital (previously known as the Kingstown General Hospital) using the step-down accounting method Both total and average unit cost estimates are provided Among the findings of note is that the cost per patient per day spent on the Maternity Ward is 57.4% higher than for the Surgical Ward. Even with the 1995 increase in user fees, the levels of subsidization for inpatient services remains relatively high at 78%-96% for public patients and 43%-72% for private patients. Ancillary services werefoundto have lower levels of subsidization and in most cases the full costs were recovered from private patients. Laboratory services are not subsidized.

Costs and Cost Analysis↗
PubMed2004

Role of solvent/non-solvent ratio on microsphere formation using the solvent removal method.

The importance of good solvent concentration in the non-solvent mixture and the non-solvent viscosity on the ability to form microspheres using solvent removal process was investigated. The higher the viscosity of the polymer solutions, the higher the concentration of good solvent needed in the nonsolvent mixture to produce microspheres. This finding was due to faster precipitation of the polymer phase. Also, the addition of a model drug, fluorescein isothiocyanate conjugated-labelled bovine serum albumin, to the polymer solution (10% poly-L-lactic acid:poly(fumaric-co-sebacic) anhydride in methylene chloride) resulted in an overall lower polymer solution viscosity (15.5 cP with fluorescein isothiocyanate conjugated-labelled bovine serum albumin as compared with 18.25 cP for blank polymer at 25 degrees C). Additionally, the effect of good solvent concentration on non-solvent viscosity was evaluated, and the viscosity decreased as the concentration of good solvent increased. The effect of good solvent concentration on the non-solvent mixture on sphere formation was of great importance. Microspheres would not form when the good polymer solvent (methylene chloride) in the non-solvent phase was too low (below 175 ml for poly-L-lactic acid or 150 ml for poly(D,L-lactidco-glycolid)) or was replaced by another good solvent such as ethyl acetate, even though the same viscosity was achieved. It was shown that the concentration of the good solvent in the non-solvent mixture was more of a controlling factor than the viscosity of the non-solvent mixture in microsphere formation and the findings support the conclusion that diffusion is the main controlling parameter in solvent removal.

Acetates↗
PubMed2004

Degradation of multi-phase microspheres fabricated via solvent removal.

Multi-phase polymer microspheres for drug encapsulation have been fabricated via solvent removal using poly(-lactic) acid (PLLA) and poly(fumaric-co-sebacic) anhydride (20:80) (P(FA:SA) (20:80)). The process by which these spheres degrade was investigated. Characterization was conducted to determine the extent of degradation of the two polymer phases over 16 weeks using scanning-electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), gel-permeation chromatography (GPC), differential-scanning calorimetry (DSC) and nuclear magnetic resonance (NMR). These experiments showed that the P(FA:SA) (20:80) phase of the multi-phase microspheres degraded faster than the PLLA phase, leaving only some of the poly(sebacic) oligomers after 16 weeks in both the in vitro and in vivo studies. These portions could remain because they were entrapped in the PLLA phase, preventing more rapid degradation. The PLLA phase showed minimal changes over the 16 week period; there was no significant change in crystallinity and only a small decrease in molecular weight in both the in vitro and in vivo studies. The in vitro study showed a rapid mass loss initially (first 3 days), followed by a fairly constant mass through 16 weeks, while the in vivo study showed a mass gain due to tissue influx.

Anhydrides↗
PubMed2002

Cognitive and behavioral performance among FMR1 high-repeat allele carriers surveyed from special education classes.

The fragile X syndrome is caused by an unstable CGG repeat sequence in the 5' untranslated region of the X-linked, FMR1 gene. When the number of repeats exceeds 200, the region is hypermethylated and the gene is silenced. The lack of the protein produced by the FMR1 gene, FMRP, causes the fragile X syndrome. Recent evidence suggests that FMR1 alleles with unmethylated long repeat tracks (40-200 repeats) may cause a specific somatic phenotype in women, premature ovarian failure, and may cause variation in the levels of FMR1 mRNA and FMRP. Because FMR1 is known to be involved in the regulation of subset of genes expressed in the brain, we investigated the variation in cognitive and/or behavioral performance among carriers of high repeat alleles. Specifically, we administered cognitive, behavioral, and adaptive performance tests to children identified with high repeat alleles who attended special education classes in Atlanta, Georgia public schools and to those with < 40 repeats drawn from the same population. Overall, we found no significant effect of repeat size and the psychometric measures in our test battery after adjustment for multiple comparisons. All scales were found to be within 1 SD standard deviation of the mean. We did find an intriguing, albeit marginally statistically significant, association in the cognitive profile among males and not females, consistent with an X-linked effect. After adjusting for the overall cognitive abilities score, Verbal Ability scores decreased and Nonverbal Reasoning scores increased with repeat number to a greater extent in males than females. Spatial Ability scores were not associated with repeat number.

Adaptation, Psychological↗
PubMed2001

Late-onset depression: genetic, vascular and clinical contributions.

BACKGROUND: Neuropsychiatric research needs to examine the relationships between aetiological, genotypic and clinical risk factors and behavioural phenotypes. These relationships can now be examined in older patients with depressive disorders. METHODS: Key behavioural features, clinical and vascular risk factors and putative genotypes for late-onset neurodegenerative disorders and/or vascular disease were recorded in 78 older patients with depression (mean age = 549 years, S.D. = 14.1) and 22 healthy control subjects (mean age = 55.5 years, S.D. = 9.6). RESULTS: Two or more vascular risks were more common in older patients (65% v. 26% of control subjects, P < 0.01), and in patients with late-onset disorders (82% v. 57% in patients with early-onset disorders, P < 0.05). Patients with late-onset depression had a higher prevalence of the homozygous or heterozygous forms of the C677T mutation of the methylenetetrahydrofolate reductase enzyme (MTHFR)(74% v. 48% in patients with early-onset disorders, P < 0.05). In a multivariate model, only presence of the MTHFR gene mutation predicted late-onset depression (odds ratio = 3.8, 95% CI = 1.1-12.9). Neither apolipoprotein E epsilon 4 or epsilon 2 was associated with depression, late-onset depression, cognitive impairment, or psychomotor change. Patients with apolipoprotein E epsilon 4 were less likely to have psychotic forms of depression. CONCLUSIONS: Patients with late-onset depression had an increased rate of the C677T MTHFR gene mutation and other vascular risk factors. This suggests that a proportion of these patients may have genetically-determined and/or other vascular aetiologies. Patients at risk of these disorders may be assisted by currently-available preventative strategies.

Adult↗
PubMed2001

Transfer of bacteria from fabrics to hands and other fabrics: development and application of a quantitative method using Staphylococcus aureus as a model.

AIMS: To develop and apply a quantitative protocol for assessing the transfer of bacteria from bleached and undyed fabrics of 100% cotton and 50% cotton + 50% polyester (poly cotton) to fingerpads or other pieces of fabric. METHODS AND RESULTS: Test pieces of the fabrics were mounted on custom-made stainless steel carriers to give a surface area of 1 cm in diameter, and each piece seeded with about 10(5) cfu of Staphylococcus aureus from an overnight broth culture; the inoculum contained 5% fetal bovine serum as the soil load. Transfer from fabric to fabric was performed by direct contact using moist and dry fabrics. Transfers from fabrics to fingerpads of adult volunteers were tested using moist, dry and re-moistened pieces of the fabrics, with or without friction during the contact. Bacterial transfer from fabrics to moistened fingerpads was also studied. All the transfers were conducted under ambient conditions at an applied pressure of 0.2 kg cm(-2). After the transfer, the recipient fingerpads or fabric pieces were eluted, the eluates spread-plated, along with appropriate controls, on tryptic soy agar and the percentage transfer calculated after the incubation of the plates for 24 h at 37 degrees C. CONCLUSION: Bacterial transfer from moist donor fabrics using recipients with moisture was always higher than that to and from dry ones. Friction increased the level of transfer from fabrics to fingerpads by as much as fivefold. Bacterial transfer from poly cotton was consistently higher when compared with that from all-cotton material. SIGNIFICANCE AND IMPACT OF THE STUDY: The data generated should help in the development of better models to assess the role fabrics may play as vehicles for infectious agents. Also, the basic design of the reported methodology lends itself to work with other types of human pathogens.

Adult↗
PubMed2000

Relationship between cross-contamination and the transmission of foodborne pathogens in the home.

Environmental microbiologists have accumulated a substantial amount of information about the relationship between cross-contamination and the transmission of foodborne pathogens in the home. This information can be translated into guidelines for safe, effective hygienic practices in the home. Such guidelines cannot be mandated but should be strongly promoted via health and hygiene agencies to the general public. Establishing consensus-based, effective hygiene guidelines will benefit the community by reducing the risk of home-based infections such as foodborne disease and by lowering the associated healthcare costs.

Environmental Microbiology↗
PubMed1999

Neo-striatal rCBF correlates of psychomotor slowing in patients with major depression.

Psychomotor slowing is a fundamental clinical feature of severe depression and is thought to reflect dysfunction within prefrontal-subcortical circuits. This study utilised a split-dose single photon emission computerised tomography (SPECT) scanning technique in association with a two-stage test of psychomotor speed. Twenty-five patients with primary depressive disorders were injected with technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) whilst performing each component of a two-stage psychomotor task. The first stage, 'simple reaction time' (RT) and the second stage, 'choice reaction time' (CRT), were each followed by 30-min SPECT scans. Regions of interest (ROIs) corresponding to the left and right neo-striatum (caudate-putamen) were drawn, and regional cerebral blood flow (rCBF) values were calculated. Importantly, the change in rCBF measure in the left neo-striatum was inversely correlated with RT (r = -0.48, P < 0.05). That is, the patients with the greatest psychomotor slowing initially showed the least increase in rCBF during the CRT condition. This effect was independent of age. The study demonstrates that a simple two-stage motor paradigm can be used to elicit rCBF correlates of psychomotor slowing in patients with primary depression. Such rCBF findings may implicate the neo-striatum in the neurobiology of major depression.

Adult↗
PubMed1999

C/EBPalpha bypasses granulocyte colony-stimulating factor signals to rapidly induce PU.1 gene expression, stimulate granulocytic differentiation, and limit proliferation in 32D cl3 myeloblasts.

Within hematopoiesis, C/EBPalpha is expressed only in myeloid cells, and PU.1 is expressed mainly in myeloid and B-lymphoid cells. C/EBPalpha-deficient mice lack the neutrophil lineage and retain monocytes, whereas PU.1-deficient mice lack monocytes and have severely reduced neutrophils. We expressed a C/EBPalpha-estrogen receptor ligand-binding domain fusion protein, C/EBPalphaWT-ER, in 32D cl3 myeloblasts. 32D cl3 cells proliferate in interleukin-3 (IL-3) and differentiate to neutrophils in granulocyte colony-stimulating factor (G-CSF). In the presence of estradiol, C/EBPalphaWT-ER induced morphologic differentiation and the expression of the myeloperoxidase, lactoferrin, and G-CSF receptor mRNAs. C/EBPalphaWT-ER also induced a G1/S cell cycle block, with induction of p27 and Rb hypophosphorylation. bcr-ablp210 prevented 32D cl3 cell differentiation. Activation of C/EBPalpha-ER in 32D-bcr-ablp210 or Ba/F3 B-lymphoid cells induced cell cycle arrest independent of terminal differentiation. C/EBPalphaWT-ER induced endogenous PU.1 mRNA within 8 hours in both 32D cl3 and Ba/F3 cells, even in the presence of cycloheximide, indicating that C/EBPalpha directly activates the PU.1 gene. However, activation of a PU.1-ER fusion protein in 32D cl3 cells induced myeloperoxidase (MPO) RNA but not terminal differentiation. Thus, C/EBPalpha acts downstream of G-CSF and upstream of PU.1, p27, and potentially other factors to induce myeloblasts to undergo granulocytic differentiation and cell cycle arrest.

Animals↗
PubMed1999

Hygiene issues in the home.

There is a growing recognition of the involvement of the home in several public health and hygiene issues and of the need to promote effective hygiene practices for the home. Hygiene practice in the home includes the categories of personal hygiene, food hygiene, environmental or surface hygiene, and home health care. This article reviews some of the hygiene risks in the home, including the role of cross-contamination via inanimate surfaces and outlines hygiene strategies and guidelines for the home as a means of breaking the chain of cross-contamination.

Communicable Disease Control↗
PubMed1999

Impact of osteoarthritis and analgesic treatment on quality of life of an elderly population.

UNLABELLED: To determine the quality of life of elderly patients with osteoarthritis (OA) compared with that of their peers with no chronic illnesses and to investigate the associations between analgesic use and quality of life. SUBJECTS: Patients >65 years of age with OA taking analgesics with (n = 33) and without (n = 26) comorbidities, and control patients with no chronic illness and not taking analgesics (n = 37). METHODS: Quality of life was assessed by the SF-36 and level of pain was measured by a visual analog scale. Multiple regression analysis was used to determine the medication characteristics and additional patient factors significantly associated with SF-36 scores. RESULTS: OA patients had significantly (p < 0.05) lower scores than control patients in all quality-of-life domains. OA patient scores were lowest for the domains of role-physical, bodily pain, and physical functioning. OA patients with comorbidities also had poorer general and mental health. Pain- and analgesic-related factors were significantly (p < 0.05) associated with physical health status, reduced vitality, general health, and social functioning. A better quality of life was associated with noncompliance, fewer visits to the physician, and taking oral nonsteroidal antiinflammatory agents. Presence of adverse drug reactions and sleep disturbance did not influence SF-36 scores significantly. CONCLUSIONS: Quality of life of elderly OA patients with and without additional comorbidities was significantly poorer than that of their healthy peers, particularly in the domains associated with physical status, but also affecting vitality, social functioning, and general health. Level of pain suffered and perceived effectiveness of analgesic medication in pain control were important factors associated with quality of life.

Aged↗
PubMed1998

Aspartylglucosaminuria in a Canadian family.

Aspartylglucosaminuria (McKusick 208400) is a lysosomopathy associated with aspartylglucosaminidase (L-aspartamido-beta-N-acetylglucosamine amidohydrolase, EC 3.5.1.26) deficiency. It has been most frequently encountered in Finland, where the regional incidence may be as high as 1 in 3600 births. In North America it is very rare, having been reported in only 8 patients. We encountered 4 patients with aspartylglucosaminuria in a Canadian family of 12 siblings. The 4 siblings affected--2 brothers and 2 sisters--were apparently normal at birth; however, their developmental milestones, particularly speech, were slow, and they acquired only a simple vocabulary. Throughout life, there was a progressive coarsening of facial features; 3 had inguinal hernia and recurrent diarrhea; all became severely retarded and by the 4th decade showed evident deterioration of both cognitive and motor skills; 2 exhibited cyclical behavioural changes. Three of the siblings have died, at 33, 39 and 44 years of age. Two died of bronchopneumonia and 1 of asphyxiation following aspiration. In the urine of all 4 siblings, and in the 1 liver examined, we found 2-acetamido-1-N-(4-L-aspartyl)-2-deoxy-beta-D-glucosamine (GlcNAc-Asn) and alpha-D-mannose-(1,6)-beta-D-mannose-(1,4)-2-acetamido- 2-deoxy-beta-D-glucose-(1,4)-2-acetamido-1-N-(4-L-aspartyl)-2-deoxy-beta - D-glucosamine (Man2-GlcNAc2-Asn). Compared with the level of activity in controls, aspartylglucosaminidase activity was less than 2% in fibroblasts from 3 of the siblings, less than 0.5% in leukocytes from 1 sibling, and less than 1% in the liver of 1 sibling, whereas other acid hydrolase activities in these tissues were normal. Ultrastructural studies of skin showed that fibroblasts, endothelial cells and pericytes contained vacuoles with fine reticulo-floccular material. Glial and neuronal cells of the central nervous system showed similar inclusions as well as others composed of concentric or parallel membranous arrays intermingled with lipid droplets.

Acetylglucosamine↗