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Biomedical subjects

S Matson

Publications and source records attributed to S Matson.

At least 19 recordsLinked to original sources
PubMed2001

Nonattendance in mammographic screening: a study of intraurban differences in Malmö, Sweden, 1990-1994.

Mammographic screening may reduce breast cancer mortality. Not all women, however, come for examination. The objective in this study from Malmö has been to assess extent to which the rate of nonattendance varies between residential areas with different sociodemographic profiles. The study is based on 32,605 women, 45 to 68 years old and living in 17 areas, who between 1990 and 1994 were invited to screening. Between age groups, the age-specific nonattendance rate ranged from 31% to 35 % (P < .01). The nonattendance rate was highest for women 65 years or older. Between residential areas, age-adjusted nonattendance rates ranged from 23% to 43% (P < .01). A socioeconomic score was developed to express the socioeconomic circumstances in the residential areas and ranged from -7.18 in the most deprived area to 5.01 in the least. Nonattendance covaried in an inverse fashion with the socioeconomic score (r = -0.78; P < .01). One of three women in this urban population did not accept the invitation to mammographic screening. Our conclusion is that women in areas with less favorable circumstances seem to be less willing to participate.

Aged↗
PubMed2000

Building an institutional commitment to pain management in long-term care facilities.

This report reviews the development, implementation and findings of an inter-institutional study directed to the goal of making pain management an institutional priority in Wisconsin long-term care facilities. A total of 87 facilities were recruited in two training cohorts. Each facility identified a team of individuals, with responsibility and authority for care policies within their institution, to participate in four structured educational programs. Each team completed an Action Plan, structured around 14 national practice indicators of an institutional commitment to pain management. At baseline, 14% of facilities had > 51% of the indicators in place; at conclusion 74% of facilities had > 51% of indicators in place. This education project was successful across training cohorts at implementing critical pain management target indicators.

Education, Continuing↗
PubMed2000

Survival of women with breast cancer in relation to smoking.

OBJECTIVE: To compare survival of patients with breast cancer who had never smoked, were smokers, and who were ex-smokers. DESIGN: Observational study. SETTING: City of Malmö, Sweden. PATIENTS: 792 patients with breast cancer diagnosed between 1977-1986 in the Malmö mammographic screening trial. INTERVENTIONS: Follow-up of breast cancer cases through record-linkage with the Swedish Cause of Death Registry. MAIN OUTCOME MEASURES: Death from breast cancer. Relative risk (RR) with 95% confidence interval (CI) of death from breast cancer was calculated for different smoking groups using Cox's proportional hazards analysis. RESULTS: During a mean follow-up of 12.1 years, 145 patients died of breast cancer. Breast cancer mortality was 1347/10(5) person-years in those who had never smoked, 1941/10(5) in smokers, and 1493/10(5) in ex-smokers. The crude RR for smokers and ex-smokers, compared with those who had never smoked were 1.44 (1.01 to 2.06) and 1.13 (0.66 to 1.94), respectively. The RR associated with smoking remained significant after adjustment for age and stage at diagnosis, 2.14 (1.47 to 3.10), and other potential confounders. CONCLUSIONS: Survival after breast cancer was, as expected, strongly related to stage at diagnosis. However, stage by stage there was considerable variation between individual patients. We conclude that differences with regard to exposure to smoking contribute to this heterogeneity.

Adenocarcinoma↗
PubMed2000

Intra-urban differences in breast cancer mortality: a study from the city of Malmö in Sweden.

STUDY OBJECTIVE: To assess whether in an urban population stage at breast cancer diagnosis is related to area of living and to what extent intra-urban differences in breast cancer mortality are related to incidence respectively stage at diagnosis. DESIGN: National registries were used to identify cases. Mortality in 17 residential areas was studied in relation to incidence and stage distribution using linear regression analysis. Areas with high and low breast cancer mortality, incidence and proportion of stage II+ tumours at diagnosis were also compared in terms of their sociodemographic profile. SETTING: City of Malmö in southern Sweden. PATIENTS: The 1675 incident breast cancer cases and 448 deaths that occurred in women above 45 years of age in Malmö 1986-96. MAIN RESULTS: Average annual age standardised breast cancer mortality ranged between residential areas, from 35/10(5) to 107/10(5), p = 0.04. Mortality of breast cancer was not correlated to incidence, r = 0.22, p = 0.39. The ratio of stage II+/0-I cancer incidence varied between areas from 0.45 to 1.99 and was significantly correlated to breast cancer mortality, r = 0.53, p = 0.03. Areas with high proportion of stage II+ cancers and high mortality/incidence ratio were characterised by a high proportion of residentials receiving income support, being foreigners and current smokers. CONCLUSIONS: Within this urban population there were marked differences in breast cancer mortality between residential areas. Stage at diagnosis, but not incidence, contributed to the pattern of mortality. Areas with high proportion of stage II+ tumours differed unfavourably in several sociodemographic aspects from the city average.

Aged↗
PubMed1999

Assessment and treatment of discomfort for people with late-stage dementia.

People with dementia have often been excluded from pain studies. However, there is evidence supporting that people with dementia experience frequent pain, often poorly assessed and undertreated, and that the etiology for pain descriptions is poorly documented. The Assessment of Discomfort in Dementia (ADD) Protocol is designed to: a) more accurately assess discomfort in people with dementia who can no longer verbally describe physical pain or affective discomfort; b) more accurately and thoroughly treat physical pain and affective discomfort; and c) decrease inappropriate use of psychotropic medication. The use of the ADD Protocol was studies with a convenience sample of 104 residents of long-term care with end-stage dementia. Use of the ADD Protocol was associated with a significant decrease in discomfort (t = 6.56, p = 0.000). The most frequently seen behavioral symptoms associated with discomfort were tense body language, sad facial expression, fidgeting, perseverant verbalizations, and verbal outburts. The ADD Protocol was also associated with a significant increase in the use of scheduled analgesics and non-pharmacological comfort interventions. The protocol was not associated with an increase in the use of prn analgesics or with prn or scheduled psychotropics. This study has provided some support for the notion that the needs of people with significant dementia can be discerned and treated.

Aged↗
PubMed1999

Pain assessment and management in the long-term care setting.

The assessment and management of pain is a significant public health problem in the United States. Long-term care facilities face unique barriers and challenges to pain management due to the large population of cognitively impaired residents, little physician contact and poor pain education for nurses and nurse assistants. In addition, common misconceptions about pain and pain treatment in the elderly along with health professional and resident fears of addiction and drug toxicity, add to the problem of pain management. The basic principles of pain treatment in long-term care are identical to all other health care settings--utilizing a combination of drug and non-drug treatments. Recent efforts to institutionalize improved pain management practices, through assessment procedures and defined pain management policies, standards and education programming, is a promising venue for systemically improving pain treatment in long-term care settings.

Aged↗
PubMed1999

Pancreatic cystic neoplasms.

Cystic neoplasms of the pancreas are relatively rare. This makes the evaluation and treatment of these tumors widely varied. The authors describe a patient who came to our hospital with complaints of abdominal pain, but no other related symptoms. Diagnostic evaluation of the patient yielded normal results, except for inspection and palpation of the abdominal areas, which revealed a large epigastric mass; this finding was confirmed subsequently by ultrasonographic examination and computed tomographic scanning. This article presents the case and reviews the literature, specifically related to diagnosis and current treatments.

Aged↗
PubMed1997

Identification of an oligodeoxynucleotide sequence motif that specifically inhibits phosphorylation by protein tyrosine kinases.

Protein tyrosine kinases (PTKs) have central roles in cellular signal transduction. We have identified a sequence motif (CGT[C]GA) in phosphorothioate-modified oligodeoxynucleotides (ODNs) that specifically inhibits the enzymatic activity of recombinant or immunoprecipitated PTK in vitro. Hexamer ODNs containing this motif block both substrate and autophosphorylation of at least four different PTKs but have no apparent effect on the enzymatic activity of a serine/threonine protein kinase. These data suggest possible new applications for ODNs and have implications for the design and interpretation of experiments using antisense or triplex ODNs.

Cell Line↗
PubMed1996

Rapid immune activation by CpG motifs in bacterial DNA. Systemic induction of IL-6 transcription through an antioxidant-sensitive pathway.

Unmethylated CpG dinucleotides (CpG motif) in bacterial DNA or synthetic oligodeoxynucleotides (CpG DNA) rapidly activate murine B cells to secrete IL-6 and IgM, as well as to proliferate. Within 30 min after CpG DNA stimulation in vivo, IL-6 mRNA levels were increased in liver, spleen, and thymus cells. Serum IL-6 protein was markedly increased within 1 h of stimulation. Treatment of a B cell line with CpG DNA led to an increase in the transcriptional activity of the IL-6 promoter. This CpG DNA-induced IL-6 production was not mediated via either a protein kinase C (PKC)-, protein kinase A (PKA)-, or nitric oxide (NO.)-dependent pathway but was inhibited by an antioxidant. In addition, the level of intracellular reactive oxygen species was increased within 20 min after CpG DNA, but not control non-CpG DNA, treatment. These results suggest that CpG DNA-induced IL-6 production is mediated through a reactive oxygen intermediate-dependent pathway. CpG DNA-mediated IL-6 production was enhanced by simultaneous signals delivered through the Ag receptor. The addition of neutralizing Abs against IL-6 to B cell cultures along with CpG oligodeoxynucleotides essentially abolished the CpG DNA-induced increased IgM secretion but had no significant effect on the B cell proliferation induced by the CpG motif. Our results suggest that the induction of IL-6 expression in response to CpG motifs in bacterial DNA may be an important immune defense mechanism that facilitates a rapid response to microbial infection.

Animals↗
PubMed1996

Oligodeoxynucleotide modifications determine the magnitude of B cell stimulation by CpG motifs.

We have recently reported that oligodeoxynucleotides (ODN) that contain a CpG dinucleotide flanked by two purines on the 5'-side and two pyrimidines on the 3'-side induce potent B cell proliferation and differentiation. The present study investigates the role of the ODN backbone in determining the magnitude of the lymphocyte stimulation. Phosphorothioate ODN were approximately 2 logs more potent than the same sequence with a phosphodiester backbone. Chimeric ODN in which the 5'- and 3'-ends were modified with nuclease-resistant internucleotide linkages induced widely varying degrees of immune activation depending on the modification. Phosphorodithioate linkages were by far the most potent and induced B cell activation at nanomolar concentrations, approximately 1 log lower than required for the next most potent modification, phosphorothioate. Methylphosphorothioate terminal linkages were slightly more potent than phosphodiester, which were in turn slightly more potent than terminal methylphosphonate-modified ODN.

Animals↗
PubMed1995

CpG motifs in bacterial DNA trigger direct B-cell activation.

Unmethylated CpG dinucleotides are more frequent in the genomes of bacteria and viruses than of vertebrates. We report here that bacterial DNA and synthetic oligodeoxynucleotides containing unmethylated CpG dinucleotides induce murine B cells to proliferate and secrete immunoglobulin in vitro and in vivo. This activation is enhanced by simultaneous signals delivered through the antigen receptor. Optimal B-cell activation requires a DNA motif in which an unmethylated CpG dinucleotide is flanked by two 5' purines and two 3' pyrimidines. Oligodeoxynucleotides containing this CpG motif induce more than 95% of all spleen B cells to enter the cell cycle. These data suggest a possible evolutionary link between immune defence based on the recognition of microbial DNA and the phenomenon of 'CpG suppression' in vertebrates. The potent immune activation by CpG oligonucleotides has implications for the design and interpretation of studies using 'antisense' oligonucleotides and points to possible new applications as adjuvants.

Animals↗
PubMed1993

Modification of antisense phosphodiester oligodeoxynucleotides by a 5' cholesteryl moiety increases cellular association and improves efficacy.

Phosphodiester oligodeoxynucleotides bearing a 5' cholesteryl (chol) modification bind to low density lipoprotein (LDL), apparently by partitioning the chol-modified oligonucleotides into the lipid layer. Both HL60 cells and primary mouse spleen T and B cells incubated with fluorescently labeled chol-modified oligonucleotide showed substantially increased cellular association by flow cytometry and increased internalization by confocal microscopy compared to an identical molecule not bearing the chol group. Cellular internalization of chol-modified oligonucleotide occurred at least partially through the LDL receptor; it was increased in mouse spleen cells by cell culture in lipoprotein-deficient medium and/or lovastatin, and it was decreased by culture in high serum medium. To determine whether chol-modified oligonucleotides are more potent antisense agents, we titered antisense unmodified phosphodiester and chol-modified oligonucleotides targeted against a mouse immunosuppressive protein. Murine spleen cells cultured with 20 microM phosphodiester antisense oligonucleotides had a 2-fold increase in RNA synthesis, indicating the expected lymphocyte activation. Antisense chol-modified oligonucleotides showed an 8-fold increase in relative potency: they caused a 2-fold increase in RNA synthesis at just 2.5 microM. The increased efficacy was blocked by heparin and was further increased by cell culture in 1% (vs. 10%) fetal bovine serum, suggesting that the effect may, at least in part, be mediated via the LDL receptor. Antisense chol-modified oligonucleotides are sequence specific and have increased potency as compared to unmodified oligonucleotides.

Animals↗
PubMed1993

Comparison of cellular binding and uptake of antisense phosphodiester, phosphorothioate, and mixed phosphorothioate and methylphosphonate oligonucleotides.

The effects of phosphorothioate (S-oligonucleotide) or terminal phosphorothioate-phosphodiester (S-O-oligonucleotides) or methylphosphonate-phosphodiester (MP-O-oligonucleotides) modifications on mouse spleen cell surface binding, uptake, and degradation were studied using fluorescein (FITC)-conjugated oligonucleotides. S-oligonucleotides had the highest cell binding and uptake, followed by S-O-, O-, and MP-O-oligonucleotides. Competition studies indicated that S-oligonucleotides have an increased affinity for cell membrane oligonucleotide binding sites, because they could completely block O-oligonucleotide binding at a molar ratio of just 0.1. Uptake of all oligonucleotides was higher in B cells than T cells and was increased by stimulation with the B-cell mitogen, lipopolysaccharide. Although our cells had been purified using conventional techniques to eliminate dead cells, there remained about 5% of cells that were dead or dying, as determined by flow cytometry using propidium iodide staining. Of note, oligonucleotide association with dead cells was approximately 50-fold greater than that with living cells. Confocal microscopy confirmed that the oligonucleotides in living cells were intracellular, and indicated little nuclear uptake by 4 h. While extensive degradation of intracellular O-oligonucleotides was apparent by 4 h, there was no detectable degradation of S-, S-O, or MP-O-oligonucleotides.

Animals↗
PubMed1992

Nonspecific suppression of [3H]thymidine incorporation by "control" oligonucleotides.

Phosphodiester oligonucleotides are rapidly degraded in spleen cell cultures. The present studies were conducted to determine whether thymidine released from degradation of such oligonucleotides could be reutilized and compete with [3H]thymidine incorporation, thereby causing nonspecific inhibition of "proliferation" assays. Our studies in mitogen-stimulated mouse spleen cells demonstrate that "control" oligonucleotides that contain thymidine can cause more than 90% inhibition of [3H]thymidine incorporation. This inhibitory effect was generally dependent on the location of the thymidine within the oligonucleotide: oligonucleotides that had 3'-terminal thymidine(s) caused more suppression than those in which thymidines were at the 5' end. All oligonucleotides caused a modest but variable inhibition of [3H]uridine incorporation. Furthermore, [3H]thymidine incorporation was partially inhibited even by oligonucleotides that did not contain thymidine. We propose that investigators who use [3H]thymidine incorporation assays to assess antisense effects do so with caution. It may be prudent to use control oligonucleotides with the same number and location of thymidine bases and to confirm [3H]thymidine incorporation assays with other measures of cell proliferation.

Animals↗