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Biomedical subjects

M Nelson

Publications and source records attributed to M Nelson.

At least 37 records · Page 2Linked to original sources
PubMed2001

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↗
PubMed2001

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

Expression and function of striatal nAChRs differ in the flinders sensitive (FSL) and resistant (FRL) rat lines.

Rats of Flinders Sensitive (FSL) and Flinders Resistant lines (FRL) differ in their susceptibility to physiological and associated behavioral responses elicited by nicotine. In the present study, we measured dopamine (DA) content in striatal dialysates to investigate the sensitivity of FSL and FRL rats to nicotine delivered locally through a microdialysis probe placed in the striatum. We also measured the expression density of striatal high-affinity nicotinic acetylcholine receptors (nAChRs), and that of mRNAs encoding for alpha3, alpha4, alpha7 and beta2 nAChR subunits in both lines. The DA content of dialysates was measured before and after a 1-min perfusion of nicotine (6, 10 or 20 nmoles/min) and the resulting DA increase was taken as a measure of the alkaloid's intrinsic activity for nAChRs involved in the release of DA. The nicotine-induced increase of striatal DA release was greater in FSL than in FRL rats for all concentrations of nicotine, suggesting that the intrinsic activity of nicotine was greater in the FSL than in the FRL rats. This was further supported by our finding that the density of high-affinity nAChRs in the striatum of FSL rats was 44% greater than in the FRL rats, whereas affinity (K(D)) was virtually the same in the two lines of rats. Also the expression of mRNAs encoding for alpha(4), alpha(7), and beta(2) subunits in the striatum was greater in FSL than in FRL rats (attomol/microg total RNA, alpha(4):98+/-10 vs. 77+/-7; alpha(7):279+/-16 vs. 184+/-16; beta(2):310+/-19 vs. 201+/-12). We hypothesize that the difference in nicotine-induced DA release in the striatum of FSL and FRL rats depends on the difference in nAChR subunit expression in the striatum between the two lines. The Flinders rats could be used as a model for nicotine self-administration studies to evaluate the susceptibilities of FSL and FRL rats to nicotine dependence.

Animals↗
PubMed2000

Recurrent anomalies of 6q25 in chondromyxoid fibroma.

Chondromyxoid fibroma is a rare benign bone tumor most commonly arising in the metaphysis of long bones in young adults. Histopathologically, chondromyxoid fibroma may be difficult to distinguish from other cartilaginous neoplasms. Recently, a pericentric inversion of chromosome 6 [inv(6)(p25q13)] has been proposed as a specific genetic marker for chondromyxoid fibroma. In this study, cytogenetic and spectral karyotypic analyses of 2 chondromyxoid fibroma cases showed clonal abnormalities of chromosome 6 but at a breakpoint on the long arm (q25) distal to that described in the pericentric inversion. These findings suggest that several distinct breakpoints on chromosome 6 are nonrandomly involved in chondromyxoid fibroma.

Adult↗
PubMed2000

Cytogenetic findings in a case of epithelioid sarcoma and a review of the literature.

Cytogenetic studies of epithelioid sarcoma, a rare malignant soft tissue neoplasm of adolescents and young adults, are few. A characteristic anomaly has not yet been identified for this sarcoma. In this study, cytogenetic studies of a primary epithelioid sarcoma of a 15-year-old male revealed the following abnormalities: t(6;8)(p25;q11.2) and add(7)(p15).

Adolescent↗
PubMed2000

Treatment of HIV-associated invasive anal cancer with combined chemoradiation.

There is an increased frequency of invasive anal cancer in HIV-seropositive men. Early treatment strategies in this patient group employed reduced dosages of chemotherapy or radiotherapy alone to reduce toxicity. Since 1989 we have used combined modality treatment consisting of chemotherapy 5-fluorouracil (5-FU) and mitomycin C, and concomitant radical radiotherapy to the pelvis (38-51 Gy in 20-30 fractions), with most patients receiving a perineal boost (10-18 Gy). 12 homosexual HIV-positive men have been treated. The median CD4 count at diagnosis of anal cancer was 209 cells/microl (range: 29-380 cells/microl), 5 had prior AIDS defining diagnoses. No patients had metastatic disease. Complete remissions were obtained in 9/11 evaluable patients and in 1 further patient following surgery. 2 patients relapsed both within 6 months of diagnosis. At a median follow-up of 4.8 years (range: 0.4-10 years), 4 patients have died (2 from anal cancer, 1 from treatment-related consequences and 1 from opportunistic infection in remission). Actuarial 2-year survival is 60% (95% confidence interval (CI): 29-91%). Grade 3 haematological toxicity was recorded in 3 patients, grade 4 and 5 gastrointestinal toxicity in 1 patient each and grade 3 skin toxicity in 1 patient. Radical chemoradiation may be given safely at conventional doses in HIV-positive patients, with a high complete response rate.

Adult↗
PubMed2000

Weekly alternating combination chemotherapy for good prognosis AIDS-related lymphoma.

Early studies reported that the major adverse prognostic factors in AIDS-related non-Hodgkin's lymphoma (ARL) are low CD4 cell count, prior AIDS defining diagnosis and poor performance status. Since 1989 we have adopted a prognosis-stratified approach for ARL. In this study, we identified a group of good prognosis patients. These patients with one or no adverse prognostic factors were treated with alternating weekly chemotherapy using the bleomycin, etoposide, vincristine, methotrexate, prednisolone/cyclophosphamide, doxorubicin (BEMOP/CA) schedule (Bower M, Block C, Gulliford T, et al. Cancer Chemother Pharmacol 1995, 38, 106-109). Modifications to the regimen with the aim of reducing toxicity were a briefer duration (12 weeks) and the addition of prophylaxis against pneumocystis and mycobacteria. Intrathecal methotrexate was administrated fortnightly to patients with Burkitt's histology, meningeal involvement or base of skull disease. 30 patients were treated, including 5 with prior AIDS, 3 with ECOG status 3 and 1 with CD4 <100/microl. The mean age was 40 (range 22-60 years), the median CD4 cell count at ARL diagnosis was 262/microl (range 44-588/microl). The International non-Hodgkin's lymphoma (NHL) prognostic factors project classifications were low risk 8 (maximum 5.4 years) (27%), low-intermediate risk 6 (20%), high-intermediate risk 11 (37%) and high risk 5 (17%). The median follow-up was 2.1 years. 3 patients withdrew from treatment within 2 weeks due to toxicity, 2 patients died within 2 weeks of starting chemotherapy. The major toxicity was myelosuppression with 14 patients developing grade 4 neutropenia. The 2-year overall survival rate is 46% (95% confidence interval (CI)=27-65%), and lymphoma-specific survival at 2 years is 59% (95% CI: 40-78%). For selected patients with good prognosis ARL 12 weeks BEMOP/CA therapy produces good overall survival at 2 years.

Adult↗
PubMed2000

Childhood nutrition and poverty.

One in three children in Britain lives in poverty (households whose income was less than 50% average earnings). Low income is associated with poor nutrition at all stages of life, from lower rates of breast-feeding to higher intakes of saturated fatty acids and lower intakes of antioxidant nutrients. Moreover, there is increasing evidence that poor nutrition in childhood is associated with both short-term and long-term adverse consequences such as poorer immune status, higher caries rates and poorer cognitive function and learning ability. These problems arise primarily because parents do not have enough money to spend on food, not because money is being spent unwisely. Policy options to improve the dietary health of poor children include: giving more money to the parents by increasing Income Support (social security) payments, providing food stamps or vouchers, and using food budget standards to inform the levels of income needed to purchase an adequate diet; feeding children directly at school (not only at lunchtime but also at breakfast or homework clubs), by providing free fruit at school, and by increasing entitlement to free food amongst children living in households with low incomes; improving access to a healthy and affordable diet by first identifying 'food deserts' and then considering with retailers and local planners how best to provide food in an economical and sustainable way. The value of using food budget standards is illustrated with data relating expenditure on food to growth in children from 'at-risk' families (on low income, overcrowded, headed by a lone parent or with four or more children under 16 years of age) living in a poor area in London. Lower levels of expenditure are strongly associated with poorer growth and health, independent of factors such as birth weight, mother's height, or risk score. The present paper provides evidence that supports the need to review Government legislation in light of nutrition-related inequalities in the health of children.

Budgets↗
PubMed2000

Persistence of episomal HIV-1 infection intermediates in patients on highly active anti-retroviral therapy.

Treatment of HIV-1-infected individuals with a combination of anti-retroviral agents results in sustained suppression of HIV-1 replication, as evidenced by a reduction in plasma viral RNA to levels below the limit of detection of available assays. However, even in patients whose plasma viral RNA levels have been suppressed to below detectable levels for up to 30 months, replication-competent virus can routinely be recovered from patient peripheral blood mononuclear cells and from semen. A reservoir of latently infected cells established early in infection may be involved in the maintenance of viral persistence despite highly active anti-retroviral therapy. However, whether virus replication persists in such patients is unknown. HIV-1 cDNA episomes are labile products of virus infection and indicative of recent infection events. Using episome-specific PCR, we demonstrate here ongoing virus replication in a large percentage of infected individuals on highly active anti-retroviral therapy, despite sustained undetectable levels of plasma viral RNA. The presence of a reservoir of 'covert' virus replication in patients on highly active anti-retroviral therapy has important implications for the clinical management of HIV-1-infected individuals and for the development of virus eradication strategies.

Anti-HIV Agents↗