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Biomedical subjects

M Nelson

Publications and source records attributed to M Nelson.

At least 109 records · Page 6Linked to original sources

Inhibition of mitotic cyclin B and cdc2 kinase activity by selenomethionine in synchronized colon cancer cells.

Selenomethionine (SeMet), an organic selenium compound, has been demonstrated to have significant chemopreventive activity. However, the mechanism of action of SeMet has yet to be identified. Previously, our laboratory found that treatment of cells with SeMet induced apoptosis and altered the cell cycle. These observations have led to further analysis of the cell cycle effects of SeMet in colon cancer cells. Synchronized HCT 116 colon cancer cells treated with 100 microM SeMet for 66 h were found to have a transient delay in G2/M phase of the cell cycle at 18 and 24 h after treatment. With this was observed an inhibition of cell growth. Coincidentally with this delay was a decrease in mitotic cyclin B RNA expression at 18 h after treatment. In addition, the cdc2 kinase activity of HCT 116 cells was decreased at 18 h. Morphological studies indicate an increase in the number of treated cells (45%) undergoing apoptosis at 66 h compared to control cells (27%). These studies demonstrate that modulation of mitotic cyclin expression and cdc2 kinase activity play a role in the ability of SeMet to inhibit tumor cell growth. A consequence of this prolonged arrest is apoptosis.

Apoptosis↗

Nursing student residency program: a model for a seamless transition from nursing student to RN.

It takes a relatively long time for new nursing graduates to become oriented and comfortable with work routines on the nursing unit. To address the problem, the authors formed a partnership among three educational programs and three hospitals. This article describes a 900-hour residency program for senior baccalaureate nursing students to ease their transition into the role of beginning-level staff nurse in an acute-care setting. The benefits to the hospitals were decreased orientation time, less turnover in staff (50% at 2 years), and lower recruitment costs.

Attitude of Health Personnel↗

Choroid plexus tumors in children: significance of stromal invasion.

OBJECTIVE: A group of choroid plexus tumors fit the cellular criteria for choroid plexus papilloma (CPP) except for invasion into the adjacent parenchyma, with associated loss of the normal villus architecture at the site of invasion. These tumors retain a benign cellular appearance. In the existing literature, it is unclear whether these tumors are classified as choroid plexus carcinomas or as CPPs. In our experience, although evidence of invasion is present, these tumors tend to exhibit benign behavior. We suggest that stromal invasion of this type remains consistent with a benign clinical course, although surgical results may demonstrate higher morbidity rates, given the invasive nature of the tumors. The failure to classify these tumors as CPPs may explain some of the variability in outcomes reported for various studies. METHODS: To study this question, clinical and histological data for children diagnosed with CPPs (either with or without stromal invasion) between 1985 and 1995 were examined. Only cases with pre- and postoperative magnetic resonance imaging data were included in the series. RESULTS: A total of 12 patients with CPPs were identified, with 4 tumors being notable for stromal invasion. After gross total tumor removal, none of the eight children with CPPs received adjuvant therapy at our institution; all are alive without evidence of tumor recurrence after surgical excision (mean, 108 mo). Of the four patients with stromal invasion, three underwent gross total resection. The one patient who underwent subtotal resection received chemotherapy at another facility. All four of these patients are alive, after a mean of 100 months of follow-up monitoring. CONCLUSION: It is recommended that CPPs with a benign cellular appearance but with evidence of local parenchymal invasion and loss of the normal villus architecture at the site of invasion be classified as CPPs. Patients with these tumors respond to surgical therapy alone, without the need for adjuvant treatment.

Child↗

Steady-state pharmacokinetics and tolerability of modafinil given alone or in combination with methylphenidate in healthy volunteers.

The potential for a pharmacokinetic (PK) drug-drug interaction between modafinil and methylphenidate, each at steady state, was investigated in an open-label, randomized, single-period study in 32 healthy male and female volunteers. All subjects received modafinil once daily orally for 28 days (200 mg on Days 1-7 and 400 mg on Days 8-28). On Days 22 to 28, half of the subjects also received 20 mg of methylphenidate orally 8 hours after their modafinil dose. PK profiles of modafinil were obtained on Days 21 and 28 and compared between the two groups. There were no statistically significant differences between the treatment groups in the mean changes in PK parameters for modafinil. Parameters for its metabolites were also similar between the groups, and all treatments were well tolerated. The results indicate that administration of low-dose methylphenidate 8 hours after treatment with modafinil does not appear to alter the steady-state pharmacokinetics of modafinil in healthy volunteers.

Adult↗

The role of NNRTIs in antiretroviral combination therapy: an introduction.

In October 2000 a meeting was convened by DuPont Pharma in Scotland to discuss the role of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in antiretroviral therapy. The Round Table meeting focused on comparisons between efavirenz and nevirapine in clinical studies and clinical practice, and the manuscripts published in this supplement report the most salient points from the presentations and discussions.

Alkynes↗

Parents' Perceptions of Primary Care: measuring parents' experiences of pediatric primary care quality.

OBJECTIVE: A measure of pediatric primary care quality that is brief, practical, reliable, and valid would be useful to patients and pediatricians, policymakers, and health system leaders. Parents have a unique perspective from which to report their experiences with their child's primary care, and these reports may be valid indicators of pediatric primary care quality. The research objective was to develop a brief parent report of their children's primary care, the Parent's Perceptions of Primary Care measure (P3C), and to test its reliability and validity as a measure of pediatric primary care quality. STUDY DESIGN: The P3C was based on the elements of primary care as defined by the Institute of Medicine. Pretesting of domain content and item clarity was accomplished via focus interviews. The P3C was developed in English and translated to Spanish, Vietnamese, and Tagalog. The 23-item P3C yields a total score, as well as subscale scores for continuity, access, contextual knowledge, communication, comprehensiveness, and coordination. The P3C was administered to 3371 parents of children in kindergarten through sixth grades in a large, urban school district. PRINCIPAL FINDINGS: The percentage of missing values for the overall sample was 1.88%, indicating acceptable feasibility. Range of measurement, assessed via floor and ceiling effects, was moderate to good. Cronbach's coefficient alpha, an indicator of scale internal consistency reliability, was 0.95 for the P3C total scale. Factor analysis supported the subscale structure, and P3C scores were higher for children with health insurance, whose parents completed the survey in English, and who had a regular physician. P3C scores were positively related to parent reports of the child's health-related quality of life. CONCLUSIONS: The P3C is a practical, reliable, and valid measure of parents' reports of pediatric primary care quality. This brief measure could be used alone, or in conjunction with other measures, to enhance outcomes and evaluate the impact of systems changes on the delivery of the main elements of primary care.

Analysis of Variance↗

Keratin 23 (K23), a novel acidic keratin, is highly induced by histone deacetylase inhibitors during differentiation of pancreatic cancer cells.

Sodium butyrate (NaBu) was shown to induce differentiation and apoptosis in the human pancreatic cancer cell line AsPC-1. A suppression subtractive hybridization-based technique was used to identify genes induced by NaBu. A novel cDNA was found to be highly up-regulated in AsPC-1 cells in response to NaBu. The gene expresses a 1.65-kb mRNA encoding a protein with an open reading frame of 422 amino acids. It has an intermediate filament signature sequence and extensive homology to type I keratins. Sequence comparison with known keratins indicated that the gene shares 42-46% amino acid identity and 60-65% similarity within the alpha-helical rod domain. The gene is named K23 (for human type I Keratin 23, KRT23). K23 mRNA was highly induced by NaBu in different pancreatic cancer cells. Trichostatin A (TSA), a potent and specific inhibitor of histone deacetylase, similarly induced K23 mRNA expression. Treatment with either actinomycin D or cycloheximide efficiently blocked the induction of K23 mRNA by NaBu/TSA. These results indicate that K23 mRNA induction by NaBu or TSA is a downstream event of histone hyperacetylation. We also demonstrated that expression of p21(WAF1/CIP1) antisense RNA efficiently blocked the induction of K23 mRNA induced by NaBu. Our results suggest that K23 is a novel member of the acidic keratin family that is induced in pancreatic cancer cells undergoing differentiation by a mechanism involving histone hyperacetylation. p21(WAF1/CIP1) serves as an important mediator during the induction process of K23 by NaBu.

Acetylation↗

Methodological issues using household budget survey expenditure data for individual food availability estimation: Irish experience in the DAFNE pan-European project. DAta Food NEtworking.

OBJECTIVE: Irish participation in the EU-supported DAta Food NEtworking (DAFNE) project required compliance with the overall aims and objectives. The Irish Household Budget Survey (HBS) expenditure data had to be transformed into a format compatible with the collaborative effort, by converting them into quantities of foodstuffs available per person per day. SETTING: The Irish 1987 HBS expenditure data on all commodities for 7705 households in the Republic of Ireland, collected using a 14-day diary kept by all members of the household aged 15 years and over. DESIGN: Following identification of 188 food items in the HBS dataset, retail prices per unit weight were sought for each food. Adjustment of prices, collected from a number of different sources, was made to those of 1987 using the Consumer Price Index. Simple models were used to estimate household food availability through application of the adjusted retail prices per unit weight to the expenditure data. The household level data were converted to food availability per person per day. An internal validation of quantities estimated using the retail prices was made using the 12 foodstuffs for which the Irish HBS collects expenses and quantities. RESULTS: The comparison of quantities published by the Irish Central Statistics Office for 12 foodstuffs in the Irish 1987 Household Budget Survey with the quantities estimated using equivalent expenditure data and corresponding retail prices showed agreement, with less than a 10% margin of error for 10 of the foods. CONCLUSION: In spite some difficulty in converting HBS food expenditure data into food availability per person per day, the DAFNE approach is potentially useful for Irish nutrition surveillance purposes and for facilitating comparisons of the Irish HBS food data with those of other European countries.

Adolescent↗

The Household Food Consumption and Anthropometric Survey in Poland.

OBJECTIVE: To provide an overview of the Household Food Consumption and Anthropometric Survey, undertaken in Poland from September to November 2000. DESIGN: A sub-sample of households participating in the countrywide, representative household budget survey (HBS) was selected to participate in the Household Food Consumption and Anthropometric Survey. Four thousand two hundred (4200) individuals provided 24-hour recalls that were subsequently evaluated. Body weight and height together with the mid-arm, waist and hip circumferences were measured. Laboratory analyses of contaminants that may be present in selected individual diets will be undertaken. SETTING: Poland, 2000. SUBJECTS: Four thousand two hundred individuals from 1362 households participating in the Polish HBS. RESULTS: Preliminary analyses of height and weight, as well as energy and nutrient intakes, were undertaken in a sub-sample of 484 boys and girls aged 10-15 years. Energy intakes were generally in line with or above the Polish Recommendations. CONCLUSIONS: Apart from serving as an important information source on individual food consumption and anthropometric status of the Polish population, the data collected through the Household Food Consumption and Anthropometric Survey will allow direct comparisons of food intake estimates, based on 24-hour recalls, with the results of the household budget survey. Such comparisons are expected to improve and refine interpretation of the data derived from both the individual nutrition survey and the household budget survey, and particularly to provide information on the importance of eating out, which is not covered in the Polish HBS.

Adolescent↗

Intrathecal pethidine as sole anaesthetic agent for operative procedures of the lower limb, inguinal area and perineum.

Intrathecal pethidine as a sole anaesthetic agent for surgical procedures of the lower limbs, perineum and inguinal areas was investigated and compared with hyperbaric Bupivacaine. A total of 90 patients were studied and randomly divided into groups 1 (bupivacaine) and 2 (pethidine). In group 2, 26 of 46 patients (59%) had their procedures successfully with intrathecal pethidine alone and did not require or request any additional sedation or analgesia. This compared to 24 of 44 patients (52.2%) in the bupivacaine group. Pethidine had a prolonged postoperative analgesia and was more cost-effective. The incidences of side effects were acceptable. (hypotension 13.6%, bradycardia 9.09%, nausea and vomiting 11.4%, and pruritus 15.9%). Pethidine can be used as a sole anaesthetic agent for operative procedures of the lower limbs; side effects are mild and can be treated.

Adult↗

Absence of association between individual thymidine analogues or nonnucleoside analogues and lipid abnormalities in HIV-1-infected persons on initial therapy.

Changes in levels of triglycerides and cholesterol during antiretroviral therapy raise concerns regarding an increased future risk of atherogenic disease and may precede the appearance of fat redistribution. Hypotheses regarding the impact of nucleoside analogues on adipocytes provide a possible explanation for metabolic and clinical fat disturbances. It is unclear whether the choice of nucleoside analogue combination or coadministration of nonnucleoside agents influences change in lipids. We performed a cross-sectional analysis of 135 persons receiving their first nucleoside analogue plus nonnucleoside-based combination antiretroviral regimen for at least 1 month and for whom cholesterol and triglyceride values were available on therapy. Univariate and multivariate regression models were used to explore the relation between cholesterol and triglycerides, as continuous variables with other variables. Both significant and nonsignificant variables from univariate analyses were evaluated in multivariate models to limit possible confounders. No association with drug choice was observed, either when comparing thymidine analogues (stavudine or zidovudine), all nucleoside analogue combinations or choice of either efavirenz or nevirapine as nonnucleoside. Age and triglyceride levels were found in a multivariate analysis to be associated with higher cholesterol. Only higher cholesterol was associated with higher triglyceride levels. In conclusion, no differences were observed between choice of drug or combination on cholesterol or triglyceride values during therapy. Older individuals may be more likely to have elevated cholesterol values.

Adult↗

Loss of 14q and 22q in gastrointestinal stromal tumors (pacemaker cell tumors).

Gastrointestinal stromal tumors (GISTs), also referred to as "gastrointestinal pacemaker cell tumors (GIPACT)" are mesenchymal neoplasms that are phenotypically similar to the interstitial cells of Cajal (ICC). Cytogenetic studies of this entity are rare and molecular cytogenetic studies utilizing chromosome-specific probes are nonexistent. In the current study, cytogenetic and molecular cytogenetic analysis of 12 histologically and immunohistochemically confirmed GISTs revealed loss of a whole chromosome 14 or region(s) of 14q in 8 tumors evaluated (67%) and loss of a whole chromosome 22 or region(s) of 22q in 8 (67%) patients. Loss of 14q and 22q were observed in histologically benign and malignant GISTs. Structural rearrangements of chromosome 1 were observed in 2 malignant GISTs. These findings indicate that loss of 14q and 22q are nonrandom, early events in GIST tumorigenesis and suggest that tumor suppressor genes responsible for the development of this neoplasm may be located on these chromosomal arms.

Adult↗

A potassium channel protein encoded by chlorella virus PBCV-1.

The large chlorella virus PBCV-1, which contains double-stranded DNA (dsDNA), encodes a 94-codon open reading frame (ORF) that contains a motif resembling the signature sequence of the pore domain of potassium channel proteins. Phylogenetic analyses of the encoded protein, Kcv, indicate a previously unidentified type of potassium channel. The messenger RNA encoded by the ORF leads to functional expression of a potassium-selective conductance in Xenopus laevis oocytes. The channel blockers amantadine and barium, but not cesium, inhibit this conductance, in addition to virus plaque formation. Thus, PBCV-1 encodes the first known viral protein that functions as a potassium-selective channel and is essential in the virus life cycle.

Amantadine↗

Reliability of measurements of pressures applied on the foot during walking by a computerized insole sensor system.

OBJECTIVE: To evaluate the reliability of measurements of foot pressures while walking using the F-scan computerized system with various insole sensors. DESIGN: Ten healthy subjects were studied. Each used four different pairs of insoles while walking for three 6-second epochs per insole. Peak pressures were recorded at the hindfoot, midfoot, and forefoot and analyzed. Each insole was made of pressure-sensitive 25 mm 2 cells, embedded in protective backing, and scanned electronically every 50 to 100 msec. SETTING AND PARTICIPANTS: Conventional tile floor in a gait laboratory on 10 consecutive normal subjects. RESULTS: The mean +/- standard deviation peak pressure recorded at the hindfoot was 11.1 +/- 2.0 psi; at the midfoot, 3.5 +/- 1.5 psi; and at the forefoot, 11.3 +/- 2.6 psi. The intrasubject mean differences were 0.2 psi at the hindfoot, 0.4 psi at the midfoot, and 0.3 psi at the forefoot. The data suggest that variability between different insoles is not significant. CONCLUSION: The pressure data show these insoles to be sufficiently reliable for use in patients when knowledge of foot pressure distribution is important for the relief of pain, and for designing and assessing appropriate corrective measures to relieve excessive pressure on the foot and to prevent development of pressure ulcers.

Adult↗