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Biomedical subjects

J Anderson

Publications and source records attributed to J Anderson.

At least 199 records · Page 11Linked to original sources

Silicone filled breast implants and the risk of fibromyalgia and rheumatoid arthritis.

OBJECTIVE: The symptoms of what has been called silicone implant associated syndrome (SIAS) and fibromyalgia (FM) are similar. It has been hypothesized that silicone (filled) breast implants (SBI) might be causally related to the development of FM. This hypothesis was investigated by comparing 508 patients with FM with 1228 control subjects. We also studied the relationship of SBI to the subsequent development of rheumatoid arthritis (RA). METHODS: Utilizing a longitudinal databank, implantation status was determined in 464 patients with RA, 508 with FM, 261 with osteoarthritis (OA) of the knee or hip, and in 503 randomly selected community controls. We obtained data on the type of implant and its temporal relationship to the onset of FM and RA. RESULTS: No association between SBI and RA was found (OR 1.66, 95% CI 0.33, 8.23, p = 0.538). No association between prior SBI and subsequent FM was found (OR 1.22, 95% CI 0.30, 4.89, p = 0.781). But one-third of the SBI in FM occurred after development of the syndrome. When all implants regardless of temporal relationship were considered, the overall relationship between any implant and the diagnosis of FM was significant at p = 0.095 (OR 2.45, 95% CI 0.86, 7.03). CONCLUSION: No relationship between prior SBI and the subsequent development of FM or RA was noted. But implants appear to be more common in patients with than in those without FM (p = 0.095). A common, predisposing set of psychosocial characteristics may be shared between those who have FM and those who undergo SBI.

Adult↗

Genes, chromosomes, and rhabdomyosarcoma.

Rhabdomyosarcomas are a heterogeneous group of malignant tumors and are the most common soft-tissue sarcoma of childhood. Rhabdomyosarcomas resemble developing skeletal muscle, notably in their expression of the MRF family of transcription factors and the PAX3 and PAX7 genes. These PAX genes are also involved through specific translocations, t(2;13)(q35;q14) and variant t(1;13)(p36;q14) in the alveolar subtype, which result in PAX3-FKHR and PAX7-FKHR fusion genes, respectively. The fusion genes are thought critically to affect downstream targets of PAX3 and PAX7 or possibly have novel targets. Similar downstream changes may also be involved in embryonal and fusion gene negative cases. Genomic amplification of such genes as MYCN, MDM2, CDK4, and PAX7-FKHR is a feature mainly of the alveolar subtype, while specific chromosomal gains, including chromosomes 2, 8, 12, and 13, are associated with the embryonal subtype. Loss of alleles and imprinting at 11p15.5 and disruption of genes such as IGF2, ATR, PTC, P16, and TP53 have also been implicated in rhabdomyosarcoma development. Whereas there is now a realistic possibility of cure in the majority of cases, there remains a subset that is resistant to multimodality therapy, including high-dose chemotherapy. Characterization of the defining molecular features of tumors that are likely to behave aggressively represents a particular challenge. Current research is leading toward a better understanding of rhabdomyosarcoma tumorigenesis, which may ultimately result in novel therapeutic strategies that increase the overall cure. Genes Chromosomes Cancer 26:275-285, 1999.

Animals↗

Numerical solution for blood flow in a centrifugal ventricular assist device.

A very small centrifugal pump, fully supported by magnetic bearings, is being developed for use as a ventricular assist device to be implanted in humans. In this paper, we apply computational fluid dynamics to model the blood flow to aid in the design of the ventricular assist device. The flow of blood through the pump has been modeled using computational fluid dynamics (CFD) software that is commercially available from AEA Technology, UK. The flow regions modeled in version 3 of the Continuous Flow Ventricular Assist Device (CF3) are the fully shrouded four bladed impeller and the two clearance regions around the impeller that are bounded by the pump hub and shroud. This paper describes the geometry and computational grids developed for the flow regions, and the equations of motion for the blood flow are developed. The overall numerically-evaluated flow rates and head rise have similar trends to the flow parameters experimentally measured, indicating that future pump designs can be effectively modeled numerically before being constructed and tested. Numerical solutions are presented and compared with experimentally-obtained overall pump performance results. These solutions are used to predict shear stress levels to be experienced by the blood flowing through the pump, and it is predicted that hemolysis will be insignificant. The solutions also indicate no regions of flow stagnation that can be a source of thrombosis in pumps. The calculations provide a viable design method to achieve improved efficiency in future versions of this pump.

Blood Flow Velocity↗

The essential Gcd10p-Gcd14p nuclear complex is required for 1-methyladenosine modification and maturation of initiator methionyl-tRNA.

Gcd10p and Gcd14p are essential proteins required for the initiation of protein synthesis and translational repression of GCN4 mRNA. The phenotypes of gcd10 mutants were suppressed by high-copy-number IMT genes, encoding initiator methionyl tRNA (tRNAiMet), or LHP1, encoding the yeast homolog of the human La autoantigen. The gcd10-504 mutation led to a reduction in steady-state levels of mature tRNAiMet, attributable to increased turnover rather than decreased synthesis of pre-tRNAiMet. Remarkably, the lethality of a GCD10 deletion was suppressed by high-copy-number IMT4, indicating that its role in expression of mature tRNAiMet is the essential function of Gcd10p. A gcd14-2 mutant also showed reduced amounts of mature tRNAiMet, but in addition, displayed a defect in pre-tRNAiMet processing. Gcd10p and Gcd14p were found to be subunits of a protein complex with prominent nuclear localization, suggesting a direct role in tRNAiMet maturation. The chromatographic behavior of elongator and initiator tRNAMet on a RPC-5 column indicated that both species are altered structurally in gcd10Delta cells, and analysis of base modifications revealed that 1-methyladenosine (m1A) is undetectable in gcd10Delta tRNA. Interestingly, gcd10 and gcd14 mutations had no effect on processing or accumulation of elongator tRNAMet, which also contains m1A at position 58, suggesting a unique requirement for this base modification in initiator maturation.

Adenosine↗

Variations between countries in invasive cardiac procedures and outcomes in patients with suspected unstable angina or myocardial infarction without initial ST elevation. OASIS (Organisation to Assess Strategies for Ischaemic Syndromes) Registry Investigators.

BACKGROUND: There are wide variations between countries in the use of invasive cardiac catheterisation and revascularisation procedures for patients with acute ischaemic syndromes. We studied the relation between rates of such procedures and rates of cardiovascular death, myocardial infarction, stroke, refractory angina, and major bleeding in a prospective, registry-based study in six countries with widely varying intervention rates. METHODS: 7987 consecutive patients presenting with unstable angina or suspected myocardial infarction without ST-segment elevation were recruited prospectively from 95 hospitals in six countries and followed up for 6 months. FINDINGS: The rates of all procedures were highest in patients in Brazil and the USA, intermediate in Canada and Australia, and lowest in Hungary and Poland. There were no significant differences in rates of cardiovascular death or myocardial infarction among these countries (4.7% overall [range 3.7-5.6] at 7 days; 11% overall [9-12] at 6 months). For the countries with the highest rates of invasive procedures (59%) versus the rest (21%) there was no difference in rate of cardiovascular death or myocardial infarction (adjusted odds ratio 0.88 at 7 days and 1.0 at 6 months). Rates of stroke were higher in Brazil and the USA than in the countries with lower intervention rates (adjusted odds ratio at 7 days 3.0, p=0.012; at 6 months 1.8, p=0.004) but rates of refractory angina at 7 days (0.7, p<0.001) and readmission for unstable angina at 6 months were lower (0.70, 0.63; both p<0.001). Comparison of results for hospitals without cardiac-catheterisation facilities and for those with such facilities gave adjusted odds ratios for cardiovascular death, myocardial infarction, or stroke at 6 months of 0.83 (10.6% vs 12.5%, p=0.05) and for refractory angina of 1.25 (19.3% vs 16.1%, p=0.09). INTERPRETATION: Higher rates of invasive and revascularisation procedures were associated with lower rates of refractory angina or readmission for unstable angina, no apparent reduction in cardiovascular death or myocardial infarction, but with higher rates of stroke. Randomised trials should assess the relative impact of conservative and more aggressive approaches to invasive cardiac procedures and revascularisations in patients with unstable angina.

Aged↗

The biological relevance of virus neutralisation sites for virulence and vaccine protection in the guinea pig model of foot-and-mouth disease.

Five neutralisation epitopes have been defined for the O1 Kaufbeuren strain of foot-and-mouth disease virus (FMDV) by neutralising murine monoclonal antibodies (Mabs). A mutant virus which is resistant to all these Mabs also resists neutralisation by bovine polyclonal sera, and this characteristic was exploited in the current study to investigate the biological relevance of neutralisation sites in FMDV virulence and vaccine protection. The five site neutralisation-resistant mutant was shown to be as pathogenic as wild-type virus in the guinea pig model of FMD. Guinea pigs were protected in cross-challenge studies from virulent wild-type and mutant viruses using either wild-type or mutant 146S antigen as inactivated whole virus vaccine. Furthermore, hyperimmune sera raised to either wild-type or mutant antigen offered passive protection against wild-type challenge, in spite of the serum raised against the mutant antigen having minimal neutralising activity in vitro. These results imply that virus neutralisation, at least as defined by the in vitro assay, may not play an essential role in the mechanism of immunity induced by whole inactivated FMDV vaccines.

Animals↗

Complex formation by all five homologues of mammalian translation initiation factor 3 subunits from yeast Saccharomyces cerevisiae.

The PRT1, TIF34, GCD10, and SUI1 proteins of Saccharomyces cerevisiae were found previously to copurify with eukaryotic translation initiation factor 3 (eIF3) activity. Although TIF32, NIP1, and TIF35 are homologous to subunits of human eIF3, they were not known to be components of the yeast factor. We detected interactions between PRT1, TIF34, and TIF35 by the yeast two-hybrid assay and in vitro binding assays. Discrete segments (70-150 amino acids) of PRT1 and TIF35 were found to be responsible for their binding to TIF34. Temperature-sensitive mutations mapping in WD-repeat domains of TIF34 were isolated that decreased binding between TIF34 and TIF35 in vitro. The lethal effect of these mutations was suppressed by increasing TIF35 gene dosage, suggesting that the TIF34-TIF35 interaction is important for TIF34 function in translation. Pairwise in vitro interactions were also detected between PRT1 and TIF32, TIF32 and NIP1, and NIP1 and SUI1. Furthermore, PRT1, NIP1, TIF34, TIF35, and a polypeptide with the size of TIF32 were specifically coimmunoprecipitated from the ribosomal salt wash fraction. We propose that all five yeast proteins homologous to human eIF3 subunits are components of a stable heteromeric complex in vivo and may comprise the conserved core of yeast eIF3.

Amino Acid Sequence↗

Hurler syndrome: II. Outcome of HLA-genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children. The Storage Disease Collaborative Study Group.

Untreated patients with Hurler syndrome (MPSIH) experience progressive neurologic deterioration and early death. Allogeneic bone marrow transplantation (BMT) ameliorates or halts this course. The Storage Disease Collaborative Study Group was formed to evaluate the effectiveness and toxicity of BMT. Effectiveness was defined as engrafted survival with continuing cognitive development. Fifty-four patients deficient in leukocyte alpha-L-iduronidase enzyme activity (median age, 1.8 years; range, 0.4 to 7.9) received high-dose chemotherapy with or without irradiation and BMT from HLA-genotypically identical sibling (GIS) or HLA-haploidentical related (HIR) donors between September 16, 1983 and July 14, 1995; all children were included in this report. Thirty-nine of 54 patients (72%) engrafted following the first BMT. The probability of grade II to IV acute graft-versus-host disease (GVHD) at 100 days was 32% for GIS and 55% for HIR patients. The probability of extensive chronic GVHD was 0% for GIS and 24% for HIR patients. The actuarial probability of survival at 5 years was 64% for all patients, 75% for GIS patients, 53% for HIR patients, and 53% for patients with donor marrow engraftment. The baseline Mental Developmental Index (MDI) was examined both for children less than and greater than 24 months of age at BMT. Children transplanted before 24 months had a mean baseline MDI of 78, while those transplanted after 24 months had a mean baseline MDI of 63 (P = . 0002). Both baseline and post-BMT neuropsychologic data were available for 26 of 30 engrafted survivors. Of 14 patients transplanted before 24 months of age, nine demonstrated developmental trajectories that were normal or somewhat slower than normal. In contrast, of 12 patients transplanted after 24 months of age, only three showed developmental trajectories that were normal or somewhat slower than normal (P = .01). For children with a baseline MDI greater than 70, there was a significant correlation between the MDI at follow-up study and leukocyte alpha-L-iduronidase enzyme activity (P = .02). Children were more likely to maintain normal cognitive development if they were fully engrafted following BMT from a donor with homozygous normal leukocyte alpha-L-iduronidase enzyme activity. Children who developed acute GVHD of grade II or worse had significantly poorer cognitive outcomes (P < .009). No difference in the post-BMT MDI was observed between patients whose preparative therapies did (n = 10; radiation dose, 300 to 1,400 cGy) or did not (n = 16) include radiation. We conclude that MPSIH patients, particularly those less than 24 months of age with a baseline MDI greater than 70, can achieve a favorable long-term outcome with continuing cognitive development and prolonged survival after successful BMT from a related donor with homozygous normal enzyme activity.

Bone Marrow Transplantation↗

Abattoir survey of sheep and goats in The Gambia.

An abattoir survey of sheep and goats was carried out in The Gambia for one year. A total of 1248 goats and 438 sheep, predominantly young females, were slaughtered and sampled. Sixty per cent of the females of both species were pregnant. There were no significant differences between the dressing percentages of different breeds and age groups. Sex and stage of pregnancy had a significant influence on carcase yields in both species. In goats the highest carcase yields were obtained during the early dry season. Most of the animals were clinically healthy and there were few pathological findings postmortem. In both species, there was a seasonal fluctuation of packed cell volume (PCV), with a minimum during the rains, and although the prevalence of trypanosomiasis was low it reduced the PCV. Faecal egg counts of Trichostrongylidae were highest during the rainy season and goats had higher faecal egg and coccidial oocyst counts than sheep. In sheep, a breed difference was observed for PCV and an age difference for egg excretion. The peak or higher rates of egg excretion occurred during the rains in both species. The immune status against peste des petits ruminants was significantly lower in goats (39 per cent) than in sheep (49.5 per cent). Antibodies against bluetongue virus were found in 62.6 per cent of goats and 55.8 per cent of sheep.

Abattoirs↗

After the strike: using facilitation in a residency training program.

Methods of alternative dispute resolution, including facilitation, can be used to identify and resolve areas of conflict. Facilitation was used by the University of Saskatchewan's Department of Family Medicine (Saskatoon division) after the strike by residents in July and August 1995 so as to allow optimal use of the remaining educational time. Through facilitation, experiences of the strike and areas of potential conflict were explored. Participants had a broad range of responses to the strike. Specific coping strategies were developed to deal with identified concerns. Although outcomes were not measured formally, levels of trust improved and collegial relationships were restored. Because so many changes occur in health care and medical education, conflict inevitably arises. Facilitation offers one way of dealing with change constructively, thereby making possible the optimal use of educational time.

Faculty, Medical↗

Molecular cloning and functional expression of mannitol-1-phosphatase from the apicomplexan parasite Eimeria tenella.

A metabolic pathway responsible for the biosynthesis and utilization of mannitol is present in the seven species of Eimeria that infect chickens, but is not in the avian host. Mannitol-1-phosphatase (M1Pase), a key enzyme for mannitol biosynthesis, is a highly substrate-specific phosphatase and, accordingly, represents an attractive chemotherapeutic target. Amino acid sequence of tryptic peptides obtained from biochemically purified Eimeria tenella M1Pase was used to synthesize degenerate oligonucleotide hybridization probes. Using these reagents, a partial genomic clone and full-length cDNA clones have been isolated and characterized. The deduced amino acid sequence of E. tenella M1Pase shows limited overall homology to members of the phosphohistidine family of phosphatases. This limited homology to other histidine phosphatases does, however, include several conserved residues that have been shown to be essential for their catalytic activity. Kinetic parameters of recombinant M1Pase expressed in bacteria are essentially identical to those of the biochemically purified preparation from E. tenella. Moreover, recombinant M1Pase is subject to active site-directed, hydroxylamine-reversible inhibition by the histidine-selective acylating reagent diethyl pyrocarbonate. These results indicate the presence of an essential histidine residue(s) at the M1Pase active site, as predicted for a histidine phosphatase.

Amino Acid Sequence↗

Biocompatibility of poly(etherurethane urea) containing dehydroepiandrosterone.

Poly(etherurethane urea) (PEUU) elastomers, with their broad range of mechanical properties and high biocompatibility, are used clinically for medical applications. However, the possibility exists for the ether soft segment of PEUU to degrade in long-term uses. To retard degradation, antioxidants that scavenge reactive oxygen intermediates are added. In this study, we incorporated dehydroepiandrosterone (DHEA), which functions by the alternate mechanism of modulating or down-regulating adherent macrophage activity, to retard the biodegradation of PEUUs. Biocompatibility of PEUU samples containing 1% DHEA, 5% DHEA, and 5% vitamin E (alpha-tocopherol) by weight were studied in vivo and in vitro. The biocompatibility was initially evaluated by examination of the inflammatory cellular exudate. Compared to PEUU without additives and PEUU with 5% vitamin E, the addition of 5% DHEA to PEUU caused a decrease in the total leukocyte exudate concentration at 4 days. The addition of 5% DHEA also caused lower macrophage adhesion and FBGC formation compared to the other materials at 7 days. Despite these short-term effects, the biocompatibility at later time points (14, 21, and 70 days) was similar for all materials. Transmission infrared analysis of the materials revealed that more than 70% of the DHEA had leached out of the samples by 3 days implantation. Furthermore, through attenuated total reflectance Fourier transform analysis and scanning electron microscopy, it was determined that unlike vitamin E, DHEA did not enhance long-term PEUU biostability. The effect of DHEA on inflammatory cell activity appeared to be dose dependent, with improved biocompatibility in vivo for higher loading levels of DHEA, but the overall effect was limited owing to the rapid diffusion of the water-soluble DHEA from the PEUU.

Animals↗

Management strategies for a better outcome in unstable coronary artery disease.

Unstable coronary artery disease is a term encompassing both unstable angina and non-Q-wave (non-ST-segment elevation) myocardial infarction. Patients with these conditions are at risk of early progression to acute myocardial infarction and death. Thus, management of these conditions must aim to reduce long-term mortality and morbidity. Risk stratification is crucial for the identification of patients whose risk of early progression is high; they may require coronary angiography and (if suitable) either percutaneous transluminal coronary angioplasty or coronary artery bypass surgery. No single variable can accurately predict risk, but considerable data are emerging to show that biochemical markers of myocardial injury, such as troponin-T and troponin-I, are valuable in combination with electrocardiographic findings and clinical features. Routine early invasive procedures (coronary angiography with or without revascularization) have not yet been shown to have any significant advantage over conservative regimens for the majority of patients. Antiplatelet, anticoagulant, and anti-ischemic agents remain the mainstay of treatment in the acute phase. New agents, such as glycoprotein IIb/IIIa receptor inhibitors and low-molecular-weight heparins, as well as antithrombins and Factor Xa inhibitors add to the treatments currently available. Thrombolytic agents are contraindicated in the absence of ST-segment elevation. After clinical stabilization, ongoing assessment should include exercise testing for all patients who are able; other imaging techniques should be used for patients unable to exercise. A profile indicating a high risk of future events is an indication for elective angiography and consideration for revascularization.

Algorithms↗

How breast cancer treatment decisions are made by women in North Dakota.

BACKGROUND: Although equally effective, women in rural midwestern states choose modified radical mastectomy (MRM) over breast conservation surgery for early stage breast cancer. This study assessed treatment decisions by the women of North Dakota. METHODS: Surveys were sent to women treated for early stage breast cancer from 1990 through 1992. Separate surveys were sent out to surgeons in the state. The questions assessed physician and patient perceptions of treatment and the decision making process. RESULTS: A majority of surgeons believed that the long-term and disease-free survival was equal and that the preference for choosing MRM was due mostly to inconvenience of radiotherapy. The women reported that the surgeon was the most influential in the treatment decision and that concerns over radiation, duration of treatment, and travel restrictions all were factors in the decision. CONCLUSIONS: Education of surgeons and patients plus the early involvement of the radiation oncologist in discussing options is essential in the treatment of early stage breast cancer.

Aged↗

Anterior enterocele following cystectomy for intractable interstitial cystitis.

PURPOSE: We clinically define the development of an anterior vaginal wall hernia following cystectomy for the management of intractable interstitial cystitis and establish surgical technique for its correction. MATERIALS AND METHODS: Of 27 women who underwent simple cystectomy and urethrectomy for intractable interstitial cystitis an anterior vaginal wall hernia developed in 3 (71, 56 and 61 years old) at 8, 14 and 16 months, respectively, postoperatively. Clinical appearance was similar to a midline cystocele but it contained bowel contents in the form of an anterior enterocele. Anterior enterocele was associated with vaginal vault prolapse in 1 patient who was treated with transvaginal sacro-spinous colpopexy. Patients with isolated anterior enterocele required a transabdominal approach with mobilization of the intestinal hernia contents and obliteration of the intervaginal abdominal wall space. RESULTS: At 12, 19 and 33 months following reconstruction prolapse has not recurred, and sexual function was restored in 1 patient. CONCLUSIONS: These cases suggest that an extended simple cystectomy performed on women with intractable interstitial cystitis may result in a weakening of the anterior vaginal wall with resultant anterior enterocele formation. When it is associated with vaginal vault prolapse a transvaginal technique may be considered but we prefer a transabdominal approach for an isolated anterior enterocele. Prevention of this entity may be warranted at the time of cystectomy.

Aged↗

Sectarian demography, territoriality and political development in Northern Ireland.

"Here we discuss, firstly, the limits of Census-based empiricism [in Northern Ireland] and the usually unacknowledged problems of data and interpretation which have resulted in a seriously misleading ¿conventional wisdom'. Secondly, we question its sectarian terms of reference, the over-identification of religion and politics, and misconceptions of ethnicity.... Thirdly, we focus on some of the flawed policy ¿solutions' associated with empiricism and sectarianism, including ¿internal' power-sharing and ¿consociational' strategies for political development."

Attitude↗

Multiple perspectives on nutrition education needs of low-income Hispanics.

As part of a multi-level nutrition intervention for low-income Hispanics (LIH) and the professionals and paraprofessionals who serve them, focus groups were used to 1) identify nutrition education needs and preferred means of receiving nutrition information, 2) identify the LIH's barriers/motivators to dietary behavior change, and 3) assess the feasibility of using abuelas (Hispanic grandmothers) as educators. Nine focus groups were conducted using trained, local bilingual and bicultural moderators. Low-income Hispanics' primary concerns were their children's nutritional habits and ways to prepare quick, nutritious meals and snacks. Their major barriers to dietary change were financial limitations, lack of time, and family customs/habits. Professionals were concerned with the lack of interagency cooperation. Paraprofessionals were most interested in training on how to teach. All audiences preferred to receive nutrition education through classes with hands-on, interactive formats. Professionals and paraprofessionals noted advantages and disadvantages to using abuelas as educators. Including three populations in the needs assessment allowed comparisons of perspectives across groups and allowed the design of nutrition education programs appropriately targeted to these populations.

Child↗