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Biomedical subjects

Mark A Miller

Publications and source records attributed to Mark A Miller.

At least 37 records · Page 2Linked to original sources
PubMed2005

Oral human brain natriuretic peptide activates cyclic guanosine 3',5'-monophosphate and decreases mean arterial pressure.

BACKGROUND: The objective of this study was to address the feasibility and the biological activity of orally administered human brain natriuretic peptide (hBNP). Proprietary technology has been developed in which short, amphiphilic oligomers are covalently attached to peptides. The conjugated peptides are intended to have an improved pharmacokinetic profile and to enable oral administration. We hypothesized that novel oral conjugated hBNP (CONJ-hBNP) increases plasma hBNP, activates cGMP, and reduces mean arterial pressure (MAP). METHODS AND RESULTS: This randomized crossover-designed study tested the biological activity of oral CONJ-hBNP compared with oral native hBNP in normal conscious dogs. Measurements of MAP, plasma hBNP, and cGMP were made at baseline (BL) and repeated at 10, 30, 60, 120, 180, and 240 minutes after oral administration. Plasma hBNP was not detectable in dogs at BL. Plasma hBNP was detected after native hBNP and CONJ-HBNP administration. However, plasma hBNP concentration was significantly higher after CONJ-hBNP than after native hBNP administration (P=0.0374 between groups). Plasma cGMP increased after CONJ-hBNP for 60 minutes (from 10.8+/-3 to 36.8+/-26 pmol/mL; P<0.05), whereas it did not change after native hBNP (P=0.001 between groups). MAP decreased at 10 minutes and remained decreased for 60 minutes after CONJ-hBNP (from 113+/-8 to 101+/-12 mm Hg after 10 minutes to 97.5+/-10 mm Hg after 30 minutes to 99+/-13 mm Hg after 60 minutes) while remaining unchanged after native hBNP (P=0.0387 between groups). CONCLUSIONS: This study reports for the first time that novel conjugated oral BNP activates cGMP and significantly reduces MAP, thus implying an efficacious coupling of CONJ-hBNP to the natriuretic receptor-A. These data advance a new concept of orally administered chronic BNP therapy for cardiovascular diseases.

Administration, Oral↗
PubMed2005

Analysis of shipboard aerosol optical thickness measurements from multiple sunphotometers aboard the R/V Ronald H. Brown during the Aerosol Characterization Experiment--Asia.

Marine sunphotometer measurements collected aboard the R/V Ronald H. Brown during the Aerosol Characterization Experiment-Asia (ACE-Asia) are used to evaluate the ability of complementary instrumentation to obtain the best possible estimates of aerosol optical thickness and Angstrom exponent from ships at sea. A wide range of aerosol conditions, including clean maritime conditions and highly polluted coastal environments, were encountered during the ACE-Asia cruise. The results of this study suggest that shipboard hand-held sunphotometers and fast-rotating shadow-band radiometers (FRSRs) yield similar measurements and uncertainties if proper measurement protocols are used and if the instruments are properly calibrated. The automated FRSR has significantly better temporal resolution (2 min) than the hand-held sunphotometers when standard measurement protocols are used, so it more faithfully represents the variability of the local aerosol structure in polluted regions. Conversely, results suggest that the hand-held sunphotometers may perform better in clean, maritime air masses for unknown reasons. Results also show that the statistical distribution of the Angstrom exponent measurements is different when the distributions from hand-held sunphotometers are compared with those from the FRSR and that the differences may arise from a combination of factors.

Journal Article↗
PubMed2005

Multinational impact of the 1968 Hong Kong influenza pandemic: evidence for a smoldering pandemic.

BACKGROUND: The first pandemic season of A/H3N2 influenza virus (1968/1969) resulted in significant mortality in the United States, but it was the second pandemic season of A/H3N2 influenza virus (1969/1970) that caused the majority of deaths in England. We further explored the global pattern of mortality caused by the pandemic during this period. METHODS: We estimated the influenza-related excess mortality in 6 countries (United States, Canada, England and Wales, France, Japan, and Australia) using national vital statistics by age for 1967-1978. Geographical and temporal pandemic patterns in mortality were compared with the genetic drift of the influenza viruses by analyzing hemagglutinin and neuraminidase sequences from GenBank. RESULTS: In North America, the majority of influenza-related deaths in 1968/1969 and 1969/1970 occurred during the first pandemic season (United States, 70%; Canada, 54%). Conversely, in Europe and Asia, the pattern was reversed: 70% of deaths occurred during the second pandemic season. The second pandemic season coincided with a drift in the neuraminidase antigen. CONCLUSION: We found a consistent pattern of mortality being delayed until the second pandemic season of A/H3N2 circulation in Europe and Asia. We hypothesize that this phenomenon may be explained by higher preexisting neuraminidase immunity (from the A/H2N2 era) in Europe and Asia than in North America, combined with a subsequent drift in the neuraminidase antigen during 1969/1970.

Disease Outbreaks↗
PubMed2005

Impact of influenza vaccination on seasonal mortality in the US elderly population.

BACKGROUND: Observational studies report that influenza vaccination reduces winter mortality risk from any cause by 50% among the elderly. Influenza vaccination coverage among elderly persons (> or =65 years) in the United States increased from between 15% and 20% before 1980 to 65% in 2001. Unexpectedly, estimates of influenza-related mortality in this age group also increased during this period. We tried to reconcile these conflicting findings by adjusting excess mortality estimates for aging and increased circulation of influenza A(H3N2) viruses. METHODS: We used a cyclical regression model to generate seasonal estimates of national influenza-related mortality (excess mortality) among the elderly in both pneumonia and influenza and all-cause deaths for the 33 seasons from 1968 to 2001. We stratified the data by 5-year age group and separated seasons dominated by A(H3N2) viruses from other seasons. RESULTS: For people aged 65 to 74 years, excess mortality rates in A(H3N2)-dominated seasons fell between 1968 and the early 1980s but remained approximately constant thereafter. For persons 85 years or older, the mortality rate remained flat throughout. Excess mortality in A(H1N1) and B seasons did not change. All-cause excess mortality for persons 65 years or older never exceeded 10% of all winter deaths. CONCLUSIONS: We attribute the decline in influenza-related mortality among people aged 65 to 74 years in the decade after the 1968 pandemic to the acquisition of immunity to the emerging A(H3N2) virus. We could not correlate increasing vaccination coverage after 1980 with declining mortality rates in any age group. Because fewer than 10% of all winter deaths were attributable to influenza in any season, we conclude that observational studies substantially overestimate vaccination benefit.

Age Distribution↗
PubMed2005

Adolescents' knowledge, beliefs, and behaviors regarding hepatitis B: Insights and implications for programs targeting vaccine-preventable diseases.

PURPOSE: To gain a better understanding of adolescents' knowledge, beliefs, and behaviors regarding hepatitis B. METHOD: Three types of data were collected as part of this investigation: (a) 45 in-depth individual interviews with staff from 20 adolescent health, sexually transmitted disease (STD), and family planning clinics; (b) 96 individual interviews with adolescents and young adults; and (c) questionnaires completed by 17,063 adolescents and young adults. All instruments focused on one or more of the following five topics: (a) knowledge about vaccines; (b) knowledge about hepatitis B; (c) barriers to vaccine acceptance, and ways to overcome these barriers; (d) benefits of the vaccine acceptance, and ways to enhance these benefits; and (e) eight hepatitis B risk factors. Interview data was analyzed using qualitative thematic note-based analyses. Survey data was analyzed using descriptive statistics and Chi-square tests. RESULTS: Adolescents and young adults seen in these clinics know very little about vaccinations in general, or hepatitis B, in particular. Adolescents exhibit low levels of perceived susceptibility, severity, response efficacy, and self-efficacy toward hepatitis B and the hepatitis B vaccine. On average, these adolescents engage in 2.36 high-risk behaviors (the most frequent of which include sexual activity, body piercing, and tattooing). Those who were sexually active, had a tattoo, had a STD, or worked with blood were significantly more likely to begin the vaccination series. CONCLUSIONS: There is a clear need for additional educational efforts regarding both vaccinations in general, and hepatitis B in particular. Though adolescents are engaging in a variety of high-risk behaviors, most perceive their risk to be low, and therefore many are not taking the necessary precautions to protect themselves.

Adolescent↗
PubMed2005

Cement-implant interface gaps explain the poor results of CMW3 for femoral stem fixation: A cadaver study of migration, fatigue and mantle morphology.

BACKGROUND: The Norwegian Arthroplasty Register reported that CMW3 cement performed poorly for femoral stem fixation. METHODS: We implanted collared, satin-finished stems (Ra = 0.35 microm) into cadaver femora using CMW3 and with Simplex as control. Cement mantle function was quantified by stem migration after 300,000 cycles of "stair climbing". Cement cracks and interface gaps were quantified in transverse sections. RESULTS: The variances of the CMW3 migrations were substantially higher than for the control (p < 0.001): subsidence for CMW3: -32 (SD 42) microm, and for Simplex: -7 (SD 9) microm (p = 0.2); retroversion for CMW3: 0.60 degrees (SD 0.25), and for Simplex: 0.37 degrees (SD 0.04) (p = 0.08). Crack length-densities were similar. CMW3 had significantly more non-apposed stem/cement interface: 52% (SD 17) versus 33% (SD 8) (p = 0.04). Migrations could be predicted by the fraction of non-apposed stem/cement interface (retroversion: R(2)=0.80, p < 0.001; subsidence: R(2) = 0.46, p = 0.02) but not by cement cracks or non-apposed cement-bone interface. INTERPRETATION: We found that increased stem/cement non-apposition resulted in increased stem migration. Early migration is known to correlate with risk of revision. Thus, the higher stem-revision risk for CMW3 cement reported by the Norwegian Arthroplasty Register may have been due to inferior and variable stem/cement apposition.

Arthroplasty, Replacement, Hip↗
PubMed2005

Review of the cost effectiveness of immunisation strategies for the control of epidemic meningococcal meningitis.

Outbreaks of meningococcal disease have caused devastation worldwide. Effective vaccines have not been used routinely, due to perceived limitations of the duration of effectiveness as well as immunogenicity when administered during infancy. Given the sporadic nature of outbreaks, the optimal use of these vaccines to control both short-term epidemic and endemic meningococcal disease has been the subject of much debate. Seven economic studies on the use of polysaccharide vaccination strategies help to highlight the relevant epidemiological and economic issues surrounding the decisions for their use. Five of these studies were based in Africa, the region where annual incidence rates can be several orders of magnitude greater than the rest of the world. These studies demonstrated that vaccination against meningococcal disease during outbreak situations is suboptimal given the inability to rapidly immunise populations in a timely fashion in resource-poor areas. However, depending on the disease incidence and the ability to deliver vaccines, the polysaccharide vaccine can be cost effective for preventive strategies when given prior to the start of outbreaks, either through presumptive vaccination or through a modified routine delivery strategy. Economic analyses of mass immunisation campaigns and modelled routine vaccination suggest that routine use of meningococcal vaccines for preventive strategies could be within the range of cost-effective public health interventions in those regions of the world where meningococcal disease is endemic. This includes the meningococcal belt of Africa, the Sahelian region.

Animals↗
PubMed2004

Multicenter study of a rapid molecular-based assay for the diagnosis of group B Streptococcus colonization in pregnant women.

BACKGROUND: Current prevention of infection due to group B Streptococcus (GBS) involves giving intrapartum antibiotics to women on the basis of either antenatal culture colonization status or presence of risk factors. METHODS: We prospectively compared the performance characteristics of a rapid molecular diagnostic test (IDI-Strep B; Infectio Diagnostic) with culture for intrapartum GBS detection after 36 weeks' gestation in 5 North American centers during the period September 2001-May 2002. Antenatal GBS screening was done according to the usual practice of participating hospitals. Two combined vaginal/anal specimens were obtained from participants during labor by use of standard techniques and processed by the same laboratories that processed the antenatal specimens. Each swab sample was processed simultaneously by culture and with IDI-Strep B. The collected specimens were randomized for order of testing of the swab samples by culture or the rapid test. RESULTS: Of enrolled women, 803 (91.1%) were eligible for analysis. The overall intrapartum GBS colonization rate by culture was 18.6% (range, 9.1%-28.7%). Compared with intrapartum culture, the molecular test had a sensitivity of 94.0% (range, 90.1%-97.8%), specificity of 95.9% (range, 94.3%-97.4%), positive predictive value of 83.8% (range, 78.2%-89.4%), and negative predictive value of 98.6% (range, 97.7%-99.5%). The molecular test was superior to antenatal cultures (sensitivity, 94% vs. 54%; P<.0001) and prediction of intrapartum status on the basis of risk factors (sensitivity, 94% vs. 42%; P<.0001). CONCLUSION: Use of this test for determination of GBS colonization during labor is highly sensitive and specific and may lead to a further reduction in rates of neonatal GBS disease.

Bacterial Typing Techniques↗
PubMed2004

Influenza and the winter increase in mortality in the United States, 1959-1999.

In economically developed countries, mortality increases distinctly during winter. Many causes have been suggested, including light-dark cycles, temperature/weather, and infectious agents. The authors analyzed monthly mortality in the United States during the period 1959-1999 for four major disease classes. The authors isolated the seasonal component of mortality by removing trends and standardizing the time series. They evaluated four properties: coincidence in mortality peaks, autocorrelation structure and autoregressive integrated moving average (ARIMA) models, magnitude, and age distribution. Peak months of mortality for ischemic heart disease, cerebrovascular disease, and diabetes mellitus coincided appropriately with peaks in pneumonia and influenza, and coefficients of autocorrelation and ARIMA models were essentially indistinguishable. The magnitude of the seasonal component was highly correlated with traditional measures of excess mortality and was significantly larger in seasons dominated by influenza A(H2N2) and A(H3N2) viruses than in seasons dominated by A(H1N1) or B viruses. There was an age shift in mortality during and after the 1968/69 pandemic in each disease class, with features specific to influenza A(H3N2). These findings suggest that the cause of the winter increase in US mortality is singular and probably influenza. Weather and other factors may determine the timing and modulate the magnitude of the winter-season increase in mortality, but the primary determinant appears to be the influenza virus.

Aged↗
PubMed2004

Phase diagram of the adhesive hard sphere fluid.

The phase behavior of the Baxter adhesive hard sphere fluid has been determined using specialized Monte Carlo simulations. We give a detailed account of the techniques used and present data for the fluid-fluid coexistence curve as well as parametrized fits for the supercritical equation of state and the percolation threshold. These properties are compared with the existing results of Percus-Yevick theory for this system.

Journal Article↗
PubMed2004

Cement microcracks in thin-mantle regions after in vitro fatigue loading.

An in vitro study of cemented femoral hip components was conducted to determine if microcracks in the cement mantle would preferentially form in thin-mantle regions as a result of cyclic fatigue loading via stair-climbing. Overall, there was not an increased amount of microcracks in thin-mantle (<2 mm) regions (number found/number expected = 0.59, P<.03). However, through cracks that extended between the stem to the bone were more prevalent in thin-mantle regions (number found/number expected = 2.93, P<.03). Although cracks form throughout the cement mantle and appear to grow at the same rate, thin-mantle regions are most likely to have through cracks after fatigue loading. This is consistent with results from at-autopsy studies of well-fixed femoral components and supports the general guideline that thin-mantle regions should be avoided in the cementing of the femoral stem.

Analysis of Variance↗
PubMed2004

A fatigue damage model for the cement-bone interface.

Loss of fixation at the cement-bone interface can contribute to clinical loosening of cemented total hip replacements. In this study, the fatigue damage response was determined for cement-bone constructs subjected to shear fatigue loading. A typical three-phase fatigue response was observed with substantial early damage, followed by a long constant damage rate region and a final abrupt increase in damage to fracture. All of the damage resulted from creep (permanent) deformation during fatigue loading and there was no loss in cyclic stiffness. Using a Von Mises equivalent stress/strain concept, a general damage model was developed to describe the fatigue creep response of the cement-bone interface under either shear or tensile fatigue loading. Time to failure was highly correlated (r2=0.971) with equivalent creep strain rate and moderately related (r2=0.428) with equivalent initial strain for the two loading regimes. The equivalent creep strain at failure (0.052+/-0.018) was found to be independent of the applied equivalent stress. A combination of the creep damage model (to describe the damage process) with a constant final equivalent strain (as a failure criteria) could be used to assess the cement-bone failure response of cemented implant systems.

Bone Cements↗
PubMed2004

Creep dominates tensile fatigue damage of the cement-bone interface.

Fatigue damage from activities of daily living has been considered to be a major cause of aseptic loosening in cemented total hip arthroplasty. The cement-bone interface is one region where loosening could occur, but to date the fatigue response of the interface has not been examined. Cement-bone specimens were prepared from fresh frozen human cadaver tissue using simulated in vivo conditions. Tensile fatigue tests to failure were performed in an environmental chamber. Loss of specimen stiffness (stiffness damage) and permanent displacement after unloading (creep damage) were found in all specimens. At failure, creep damage accounted for the majority (79.9+/-10.6%) of the total strain damage accumulation at failure (apparent strain, epsilon=0.0114+/-0.00488). A power law relationship between strain-damage rate and time-to-failure showed that the strain-damage rate was an excellent predictor of the fatigue life of the cement-bone interface. The S-N response of the interface was obtained as a function of the applied stress ratio and the initial apparent strain. The total motion between cement and bone (72.2+/-29.8 microm) prior to incipient failure due to both stiffness and creep fatigue damage may be sufficient to result in fibrous tissue formation and contribute to eventual clinical loosening.

Aged↗
PubMed2004

Recombinant replication-restricted VSV as an expression vector for murine cytokines.

Vesicular stomatitis virus (VSV) is a prototypic non-segmented, negative-strand RNA virus that rapidly and efficiently shuts down the production of host cell-encoded proteins and utilizes the cell's protein production machinery to express high levels of virally encoded proteins. In an effort to take advantage of this characteristic of VSV, we have employed a reverse genetics system to create recombinant forms of VSV encoding a variety of murine cytokines. Previous studies have revealed that cells infected with recombinant VSV that lack expression of the surface glycoprotein (G protein), designated deltaG-VSV, more efficiently express and secrete recombinant proteins than do recombinant "wild-type" VSV. Therefore, murine cytokine-expressing recombinants were produced as deltaG viruses. Propagation of these deltaG viruses in cells that transiently express G protein in vitro results in G-complemented virions that can infect cells, shut down host protein synthesis, and express at high levels each virally encoded protein (including the designated cytokine). We assessed the ability of each deltaG-VSV construct to express recombinant cytokine by infecting BHK cells and then monitoring/measuring the production of the desired cytokine. When possible, the bioactivity of the cytokine products was also measured. The results presented here reveal that large quantities of bioactive cytokines can be produced rapidly and inexpensively using deltaG-VSV as a protein expression system.

Animals↗