PubMed Health⌕ Search

Biomedical subjects

Mark A Miller

Publications and source records attributed to Mark A Miller.

At least 19 recordsLinked to original sources
PubMed2007

Stem-cement porosity may explain early loosening of cemented femoral hip components: experimental-computational in vitro study.

A combination of laboratory experiment and computational simulation was performed to assess the role of interface porosity on stem migration. The early motion of in vitro prepared cemented femoral components was measured during application of cyclic stair climbing loads. Following testing, transverse sections were obtained and the distribution of pores at the stem-cement interface was determined. Finite element models of cemented stem constructs were developed and a scheme was implemented to randomly assign pores to the stem-cement interface. For a series of 14 in vitro prepared components, pore fractions at the stem-cement interface ranged from 23% to 67%. The majority of pores at the stem-cement interface were less than 1 mm in length with a mean length of 1.27 +/- 2.7 mm and thickness of 0.12 +/- 0.11 mm. For stems with large pore fractions, pores tended to coalesce in longer extended gaps over the stem surface. Finite element and experimental models both revealed strong positive correlations (r(2) = 0.55-0.72; p < 0.0001) between stem-cement pore fraction and stem internal rotation, suggesting that the presence and extent of pores could explain the early motion of the stems. There was an increased volume of cement at risk of fatigue failure with increasing stem migration. Pore fractions greater than 30% resulted in large increases in stem internal rotation, suggesting that attempts to maintain surface porosity at or below this level may be desirable to minimize the risk of clinical loosening.

Aged↗
PubMed2007

The role of cement viscosity on cement-bone apposition and strength: an in vitro model with medullary bleeding.

We compared the mechanical and morphological characteristics of cement-bone structures created with either standard- or low-viscosity cement using a human cadaver model that simulated intramedullary bleeding. The goal is to determine if the viscosity of the cement would affect the strength of the cement-bone interface and the degree of apposition between the cement and bone. The tensile strength of cement-bone constructs with standard-viscosity cement (2.42 +/- 1.55 MPa) was 21% stronger than with low-viscosity cement (2.00 +/- 1.51 MPa, P = .034). Cement-bone apposition was positively correlated (r2 = 0.29, P <. 0001) with the strength of the interface. There was 15% greater apposition between cement and bone (P = .036) for standard-viscosity cement. Low-viscosity cement may be less effective in displacing bone marrow and in preventing hemodynamic backflow, resulting in less apposition and a weaker interface.

Aged, 80 and over↗
PubMed2006

The Bla2 beta-lactamase from the live-vaccine strain of Francisella tularensis encodes a functional protein that is only active against penicillin-class beta-lactam antibiotics.

Francisella tularensis ssp. tularensis is a category A select agent and the causal organism for the zoonotic disease tularemia. The vast majority of F. tularensis isolates are beta-lactamase-positive. beta-lactamase production is widely believed to be responsible for the inefficacy of beta-lactams in the treatment of tularemia. In this study, we report the cloning and characterization of the two chromosomally encoded F. tularensis ssp. holarctica live-vaccine strain (LVS) beta-lactamases. The two LVS beta-lactamases were homologous to F. tularensis Schu S4 open reading frames FTT0681c and FTT0611c and have been named bla1 (LVS) and bla2 (LVS), respectively. Recombinant expression in Escherichia coli suggested that bla1 (LVS) did not encode a functional beta-lactamase, whereas bla2 (LVS) encoded a functional beta-lactamase that hydrolyzed penicillins but was inactive against third-generation cephalosporins, including cefprozil. As both LVS and Schu S4 were susceptible to cefprozil, we developed three new shuttle vectors based on selection for the production of the Bla(shv-2) extended-spectrum beta-lactamase with cefprozil. The resulting shuttle vectors were suitable for recombinant gene expression and complementation studies in LVS and Schu S4.

Anti-Bacterial Agents↗
PubMed2006

Influenza-related mortality in the Italian elderly: no decline associated with increasing vaccination coverage.

We investigated trends in influenza-related mortality among the elderly population in Italy associated with increased vaccination coverage. Using Italian vital statistics data, we studied monthly death rates for pneumonia and influenza and all-cause for persons >/=65 years of age by 5-year age groups for 1970-2001. Using a classic seasonal regression modelling approach, we estimated the age-specific seasonal excess mortality rates among Italian elderly as a measure of influenza-related deaths. We studied trends in excess mortality after adjusting for population aging and analyzing separately seasons dominated by the severe A/H3N2 subtype and those dominated by other circulating influenza subtypes. After the late 1980s, no decline in age-adjusted excess mortality was associated with increasing influenza vaccination distribution primarily targeted for the elderly. These findings suggest that either the vaccine failed to protect the elderly against mortality (possibly due to immune senescence), and/or the vaccination efforts did not adequately target the frailest elderly. As in the US, our study challenges current strategies to best protect the elderly against mortality, warranting the need for better controlled trials with alternative vaccination strategies.

Aged↗
PubMed2006

Transmissibility and mortality impact of epidemic and pandemic influenza, with emphasis on the unusually deadly 1951 epidemic.

There are important gaps in our current understanding of the influenza virus behavior. In particular, it remains unclear why some inter-pandemic seasons are associated with unusually high mortality impact, sometimes comparable to that of pandemics. Here we compare the epidemiological patterns of the unusually deadly 1951 influenza epidemic (A/H1N1) in England and Wales and Canada with those of surrounding epidemic and pandemic seasons, in terms of overall mortality impact and transmissibility. Based on the statistical and mathematical analysis of vital statistics and morbidity epidemic curves in these two countries, we show that the 1951 epidemic was associated with both higher mortality impact and higher transmissibility than the 1957 and 1968 pandemics. Surprisingly in Liverpool, considered the 'epicenter' of the severe 1951 epidemic, the mortality impact and transmissibility even surpassed the 1918 pandemic.

Communicable Disease Control↗
PubMed2006

Synchrony, waves, and spatial hierarchies in the spread of influenza.

Quantifying long-range dissemination of infectious diseases is a key issue in their dynamics and control. Here, we use influenza-related mortality data to analyze the between-state progression of interpandemic influenza in the United States over the past 30 years. Outbreaks show hierarchical spatial spread evidenced by higher pairwise synchrony between more populous states. Seasons with higher influenza mortality are associated with higher disease transmission and more rapid spread than are mild ones. The regional spread of infection correlates more closely with rates of movement of people to and from their workplaces (workflows) than with geographical distance. Workflows are described in turn by a gravity model, with a rapid decay of commuting up to around 100 km and a long tail of rare longer range flow. A simple epidemiological model, based on the gravity formulation, captures the observed increase of influenza spatial synchrony with transmissibility; high transmission allows influenza to spread rapidly beyond local spatial constraints.

Adult↗
PubMed2006

The effect of low-viscosity cement on mantle morphology and femoral stem micromotion: a cadaver model with simulated blood flow.

BACKGROUND: Limited data exist on the performance of low-viscosity cement in clinically realistic cadaver models. METHODS: Paired stem/cement/femur constructs were generated with low-viscosity and standard-viscosity cements. The constructs were created and tested under simulated in vivo conditions, for which novel techniques were developed during this study. Mantle function was quantified by stem/cortex micromotions over 105cycles of "stair-climbing". Mantle morphology was determined from transverse sections. RESULTS: Penetration of low-viscosity cement was greater proximally but less distally (p = 0.02). Low-viscosity cement resulted in more stem retroversion (p = 0.04), but there was no difference in subsidence (p = 0.4). Low-viscosity cement mantles had greater fractions of non-apposed interface (p = 0.006). Fraction of non-apposed interface predicted stem retroversion (R2 = 0.64, p = 0.002). INTERPRETATION: Low-viscosity cement resulted in inferior cement mantles. Early micromotion was reduced by better interface apposition. The greater stem retroversion of low-viscosity cement would probably lead to higher revision rates. Early stem migration is due to interface non-apposition. Techniques should be developed to reduce non-apposition of cemented interfaces.

Aged↗
PubMed2006

Enterococcus gallinarum N04-0414 harbors a VanD-type vancomycin resistance operon and does not contain a D-alanine:D-alanine 2 (ddl2) gene.

Enterococcus gallinarum N04-0414 (MIC for vancomycin, 256 microg/ml) harbored a vanD-type vancomycin resistance operon as well as the intrinsic vanC1 operon. The D-Ala:D-Ala ligase 2 gene (ddl2) was not present in the strain, though it is found downstream of the vanS gene from the vanC operon in E. gallinarum ATCC 49573 and 19 other E. gallinarum strains tested.

Alanine↗
PubMed2006

Stochastic processes are key determinants of short-term evolution in influenza a virus.

Understanding the evolutionary dynamics of influenza A virus is central to its surveillance and control. While immune-driven antigenic drift is a key determinant of viral evolution across epidemic seasons, the evolutionary processes shaping influenza virus diversity within seasons are less clear. Here we show with a phylogenetic analysis of 413 complete genomes of human H3N2 influenza A viruses collected between 1997 and 2005 from New York State, United States, that genetic diversity is both abundant and largely generated through the seasonal importation of multiple divergent clades of the same subtype. These clades cocirculated within New York State, allowing frequent reassortment and generating genome-wide diversity. However, relatively low levels of positive selection and genetic diversity were observed at amino acid sites considered important in antigenic drift. These results indicate that adaptive evolution occurs only sporadically in influenza A virus; rather, the stochastic processes of viral migration and clade reassortment play a vital role in shaping short-term evolutionary dynamics. Thus, predicting future patterns of influenza virus evolution for vaccine strain selection is inherently complex and requires intensive surveillance, whole-genome sequencing, and phenotypic analysis.

Antigenic Variation↗
PubMed2006

1951 influenza epidemic, England and Wales, Canada, and the United States.

Influenza poses a continuing public health threat in epidemic and pandemic seasons. The 1951 influenza epidemic (A/H1N1) caused an unusually high death toll in England; in particular, weekly deaths in Liverpool even surpassed those of the 1918 pandemic. We further quantified the death rate of the 1951 epidemic in 3 countries. In England and Canada, we found that excess death rates from pneumonia and influenza and all causes were substantially higher for the 1951 epidemic than for the 1957 and 1968 pandemics (by > or =50%). The age-specific pattern of deaths in 1951 was consistent with that of other interpandemic seasons; no age shift to younger age groups, reminiscent of pandemics, occurred in the death rate. In contrast to England and Canada, the 1951 epidemic was not particularly severe in the United States. Why this epidemic was so severe in some areas but not others remains unknown and highlights major gaps in our understanding of interpandemic influenza.

Adolescent↗
PubMed2006

Review of reported cholera outbreaks worldwide, 1995-2005.

The global temporal and spatial distribution of cholera is underappreciated, given the lack of surveillance in endemic areas and economic disincentives to report outbreaks. To judge the use of specific novel interventions such as vaccines or anti-secretory agents, we compiled a database and analyzed cholera reports from the Program for Monitoring Emerging Diseases from 1995 to 2005. Of the 632 reports meeting the search criteria, 66% originated in Sub-Saharan Africa, followed by 16.8% from Southeast Asia. Reported outbreaks in Africa tended to be larger in size. The most common risk factors were water source contamination, heavy rainfall and flooding, and population dislocation. While cholera reporting is sub-optimal, this review provides a detailed sub-national quantification of cholera, identifies foci of endemicity in Africa, and describes risk factors by region. We highlight the need for more extensive outbreak reporting to justify investments in new interventions.

Cholera↗
PubMed2005

Novel structural motifs in clusters of dipolar spheres: knots, links, and coils.

We present the structures of putative global potential energy minima for clusters bound by the Stockmayer (Lennard-Jones plus point dipole) potential. A rich variety of structures is revealed as the cluster size and dipole strength are varied. Most remarkable are groups of closed-loop structures with the topology of knots and links. Despite the large number of possibilities, energetically optimal structures exhibit only a few such topologies.

Journal Article↗
PubMed2005

A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality.

BACKGROUND: In March 2003, several hospitals in Quebec, Canada, noted a marked increase in the incidence of Clostridium difficile-associated diarrhea. METHODS: In 2004 we conducted a prospective study at 12 Quebec hospitals to determine the incidence of nosocomial C. difficile-associated diarrhea and its complications and a case-control study to identify risk factors for the disease. Isolates of C. difficile were typed by pulsed-field gel electrophoresis and analyzed for binary toxin genes and partial deletions in the toxin A and B repressor gene tcdC. Antimicrobial susceptibility was evaluated in a subgroup of isolates. RESULTS: A total of 1703 patients with 1719 episodes of nosocomial C. difficile-associated diarrhea were identified. The incidence was 22.5 per 1000 admissions. The 30-day attributable mortality rate was 6.9 percent. Case patients were more likely than matched controls to have received fluoroquinolones (odds ratio, 3.9; 95 percent confidence interval, 2.3 to 6.6) or cephalosporins (odds ratio, 3.8; 95 percent confidence interval, 2.2 to 6.6). A predominant strain, resistant to fluoroquinolones, was found in 129 of 157 isolates (82.2 percent), and the binary toxin genes and partial deletions in the tcdC gene were present in 132 isolates (84.1 percent). CONCLUSIONS: A strain of C. difficile that was resistant to fluoroquinolones and had binary toxin and a partial deletion of the tcdC gene was responsible for this outbreak of C. difficile-associated diarrhea. Exposure to fluoroquinolones or cephalosporins was a risk factor.

Aged↗
PubMed2005

Malaria chemoprophylaxis and the serologic response to measles and diphtheria-tetanus-whole-cell pertussis vaccines.

BACKGROUND: Acute malaria has been associated with a decreased antibody response to tetanus and diphtheria toxoids, meningococcal, salmonella, and Hib vaccines. Interest in giving malaria drug therapy and prevention at the time of childhood immunizations has increased greatly following recent trials of intermittent preventive therapy during infancy (IPTi), stimulating this re-analysis of unpublished data. The effect of malaria chemoprophylaxis on vaccine response was studied following administration of measles vaccines and diphtheria-tetanus-whole cell pertussis (DTP) vaccines. METHODS: In 1975, six villages divided into two groups of children < or = 74 months of age from Burkina Faso, were assigned to receive amodiaquine hydrochloride chemoprophylaxis (CH+) every two weeks for seven months or no chemoprophylaxis (CH-). After five months, children in each group received either one dose of measles or two doses of DTP vaccines. RESULTS: For recipients of the measles vaccine, the seroconversion rates in CH+ and CH- children, respectively, were 93% and 96% (P > 0.05). The seroresponse rates in CH+ and CH- children respectively, were 73% and 86% for diphtheria (P > 0.05) and 77% and 91% for tetanus toxoid (P > 0.05). In a subset analysis, in which only children who strictly adhered to chemoprophylaxis criteria were included, there were, likewise, no significant differences in seroconversion or seroresponse for measles, diphtheria, or tetanus vaccines (P > 0.05). While analysis for pertussis showed a 43% (CH+) and 67% (CH-) response (P < 0.05), analyses using logistic regression to control for sex, age, chemoprophylaxis, weight-for-height Z-score, and pre-vaccination geometric mean titer (GMT), demonstrated that chemoprophylaxis was not associated with a significantly different conversion rate following DTP and measles vaccines. Seven months of chemoprophylaxis decreased significantly the malaria IFA and ELISA GMTs in the CH+ group. CONCLUSION: Malaria chemoprophylaxis prior to vaccination in malaria endemic settings did not improve or impair immunogenicity of DTP and measles vaccines. This is the first human study to look at the association between malaria chemoprophylaxis and the serologic response to whole-cell pertussis vaccine.

Amodiaquine↗
PubMed2005

IL-12-assisted immunization against Listeria monocytogenes using replication-restricted VSV-based vectors.

Co-administration of IL-12 with vaccine immunogens has proven to be an effective strategy for eliciting potent Th1-biased immunity. Unfortunately, the use of IL-12 as a vaccine component has been limited because it is unstable at ambient temperatures, expensive to produce, and toxic when administered at excessive dosages. Using reverse genetics, we created a recombinant replication-restricted vesicular stomatitis virus that expresses large quantities of an IL-12 fusion protein (VSVDeltaG-IL12F), but can only establish a single round of infection because the genome does not encode the viral glycoprotein (G protein) that is required for viral entry into host cells. Here, we report that immunization of mice with a poorly immunogenic listerial antigen preparation (LMAg) in combination with VSVDeltaG-IL12F elicits potent T cell- and B cell-mediated responses that confer protective listerial immunity.

Adjuvants, Immunologic↗
PubMed2005

Are antibodies to the capsular polysaccharide of Neisseria meningitidis group B and Escherichia coli K1 associated with immunopathology?

As polysialic acid (PSA), the capsule of Group B meningococcus (GBM) and Escherichia coli K1, is a component of mammalian glycopeptides, there is concern that vaccines against PSA could induce immunopathology. Purified PSA is not immunogenic; however, as a component of bacteria or bound to proteins, it induces protective antibodies. In this review, we did not unearth data indicating an association of IgG anti-PSA with immunopathology in experimental animals or humans. We found no increased incidence of autoimmunity from GBM infections in our review of the natural history/sequellae of Neisseria meningitis infections. Accordingly, we propose that clinical trials of PSA conjugate vaccines, be considered.

Animals↗