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C J Murray

Publications and source records attributed to C J Murray.

At least 19 recordsLinked to original sources
PubMed1997

Health expenditures in Latin America and the Caribbean.

This paper presents the results of a study commissioned by the Latin American and Caribbean Technical Department of the World Bank to document and analyze health expenditures in Latin America and the Caribbean. In 1990, the countries of this region spent US$ 69 billion on health, with an average per capita health expenditure of US$ 162. On average, the countries spent 6.2% of their GDP on health, with the expenditures divided about equally between the public and private sectors. In both the public and private sectors, per capita health expenditures were positively and significantly correlated with per capita income. However, this relationship holds only for the public sector, when health expenditures are measured as a proportion of GDP. While several poorer countries were dependent on external assistance, with increasing income, the countries relied more on public expenditures to finance health care. Based on the limited time series data, it is evident that there was a considerable variation among countries regarding the proportion spent on capital investments, primary health care, and drugs, but not on salaries. Looking ahead, with increasing economic development, the proportion of GDP spent on health, along with public health expenditure as a proportion of total health expenditure, is likely to increase rapidly, while aid dependency is likely to decline.

Caribbean Region↗
PubMed1996

A low-barrier hydrogen bond in subtilisin: 1H and 15N NMR studies with peptidyl trifluoromethyl ketones.

The N delta 1 proton of His 64 forms a hydrogen bond with Asp 32, as part of the catalytic triad in serine proteases of the subtilisin family. His 64 in subtilisin has been studied by 1H and 15N NMR spectroscopy in the presence and absence of peptidyl trifluoromethyl ketones (TFMKs) that are transition state analog inhibitors. For subtilisin Carlsberg, the downfield resonance of the imidazolium N delta 1 proton is approximately 18.3 ppm and the D/H fractionation factor is 0.55 +/- 0.04 at pH 5.5 (11 degrees C), and 0.63 +/- 0.04 (5 degrees C) and 0.68 +/- 0.04 at pH 6 (11 degrees C). In the complex between subtilisin Carlsberg and Z-L-leucyl-L-leucyl-L-phenylalanyltrifluoromethyl ketone (Z-LLF-CF3) at pH values between 6.5 and 10.6, His 64 remains positively charged, and the D/H fractionation factor of its N delta 1 proton is 0.85 +/- 0.05. In the complex between a subtilisin variant from Bacillus lentus and Z-LLF-CF3, the proton resonance at 18.8 ppm is correlated with a 15N resonance at 197.6 ppm downfield from liquid NH3 with a 1JNH of 81 Hz. The chemical shifts of subtilisin complexes with peptidyl TFMKs are among the most downfield shifts reported for any protein. At pH 9.5, His 64 is neutral and the D/H fractionation factor increases to 1.2 with a chemical shift of 15.0. His 64 is positively charged in the free enzyme at low pH, the inhibitor hemiketal complex at neutral pH, and the transition state for amide bond hydrolysis. These data thus provide indirect evidence for the presence of a low-barrier hydrogen bond in the catalytic mechanism of subtilisin proteases.

Bacterial Proteins↗
PubMed1996

Active-site titration of serine proteases using a fluoride ion selective electrode and sulfonyl fluoride inhibitors.

We report a general procedure for the determination of active enzyme concentrations for serine proteases. The method relies on the measurement of fluoride ion released from sulfonyl fluorides upon reaction with the active-site serine using an ion selective electrode. The results have been independently confirmed by amino acid analyses of subtilisins and by spectrofluorometric and spectrophotometric titrations. The minimal enzyme concentration detectable is 1-10 microM protease. The method is insensitive to color and turbidity of the sample and is therefore useful for measuring protease concentration in broth solutions. The active enzyme concentration of subtilisin BPN' from Bacillus amyloliquefaciens determined by titration with phenylmethylsulfonyl fluoride is 25% higher than the concentration determined using the spectrophotometric burst titrant N-trans-cinnamoylimidazole. Analysis of the pre-steady-state burst amplitude and kinetics suggests that the extinction coefficient for the cinnamoyl acyl-enzyme is larger than previously measured and a significant fraction of the enzyme is present as an unproductive ES2 complex. The molar extinction coefficient at 280 nm for subtilisin BPN' is 26.5 mM-1 cm-1 and for subtilisin from Bacillus lentus is 22.5 mM-1 cm-1.

Bacillus↗
PubMed1996

Secondary H/T and D/T isotope effects in enzymatic enolization reactions. Coupled motion and tunneling in the triosephosphate isomerase reaction.

Secondary kH/kT kinetic isotope effects in H2O and kH/kT or kD/kT isotope effects in D2O have been measured for the triosephosphate isomerase-catalyzed conversion of dihydroxyacetone 3-phosphate (DHAP) to D-glyceraldehyde 3-phosphate. The proton transfer steps are made rate-limiting using [1(R)-2H]-labeled substrate in D2O to slow the chemical steps, relative to product release. After a small correction for the beta-equilibrium isotope effect for dehydration of DHAP, the H/T kinetic isotope effect kH/kT = 1.27 +/- 0.03 for [1(R)-2H,(S)-3H]-labeled substrate in D2O is subtantially larger than the equilibrium isotope effect for enolization of DHAP, KH/KT = 1.12. The H/T isotope effect is related to the D/T isotope effect with a Swain-Schaad exponent y = 4.4 +/- 1.3. These results are consistent with coupled motion of the C-1 primary and secondary hydrogens of DHAP and tunneling. Large secondary kinetic isotope effects are a general feature of enzymatic enolization reactions while nonenzymatic enolization reactions show secondary kinetic isotope effects that are substantially smaller than equilibrium effects [Alston, W. A., II, Haley, K., Kanski, R., Murray, C.J., & Pranata, J. (1996) J. Am. Chem Soc., 118, 6562-6569]. Possible origins for these differences in transition state structure are discussed.

Animals↗
PubMed1996

The incremental effect of age-weighting on YLLs, YLDs, and DALYs: a response.

When disability-adjusted life years (DALYs) were first formulated, the effect of age-weighting on years of life lost due to death at each age as well as the different effect on short- and medium-term disability were taken into consideration. While there is considerable scope for discussion on the actual values that are incorporated into DALYs, the present article argues that once the values have been chosen we should accept the consequences of the choice.

Age Factors↗
PubMed1994

Salmonella serovars and phage types in humans and animals in Australia 1987-1992.

This report summarises the range of Salmonella serovars and phage types found in humans in Australia during the years 1987 to 1992 inclusive, and compares them with serovars from food animals and raw meats for the same period. It also compares the major serovars found from different animal sources with their frequency from humans. The common serovars from animal feeds are compared with their frequency from animals.

Animal Feed↗
PubMed1994

National health expenditures: a global analysis.

As part of the background research to the World development report 1993: investing in health, an effort was made to estimate public, private and total expenditures on health for all countries of the world. Estimates could be found for public spending for most countries, but for private expenditure in many fewer countries. Regressions were used to predict the missing values of regional and global estimates. These econometric exercises were also used to relate expenditure to measures of health status. In 1990 the world spent an estimated US$ 1.7 trillion (1.7 x 10(12) on health, or $1.9 trillion (1.9 x 10(12)) in dollars adjusted for higher purchasing power in poorer countries. This amount was about 60% public and 40% private in origin. However, as incomes rise, public health expenditure tends to displace private spending and to account for the increasing share of incomes devoted to health.

Financing, Government↗
PubMed1994

External assistance to the health sector in developing countries: a detailed analysis, 1972-90.

This study, which was conducted for the World Bank's World development report 1993: investing in health, provides an objective analysis of the external assistance to the health sector by quantifying in detail the sources and recipients of such assistance in 1990, by analysing time trends for external assistance to the health sector over the last two decades, and, to the extent possible, by describing the allocation of resources to specific activities in the health sector. The main findings of the study are that total external assistance to the health sector in 1990 was US$ 4800 million, or only 2.9% of total health expenditures in developing countries. After stagnation in real terms during the first half of the 1980s, health sector assistance has been increasing since 1986. Despite their small volume, external assistance at the margins may play a critical role in capital investment, research and strategic planning. The study confirms prior findings that health status variables per se are not related to the amount of aid received. Comparing investments to the burden of disease shows tremendous differences in the funding for different health problems. A number of conditions are comparatively under-financed, particularly noncommunicable diseases and injuries.

Communicable Disease Control↗
PubMed1994

Cost-effectiveness analysis and policy choices: investing in health systems.

The role of health systems infrastructure in studies of cost-effectiveness analysis and health resource allocation is discussed, and previous health sector cost-effectiveness analyses are cited. Two substantial difficulties concerning the nature of health system costs and the policy choices are presented. First, the issue of health system infrastructure can be addressed by use of computer models such as the Health Resource Allocation Model (HRAM) developed at Harvard, which integrates cost-effectiveness and burden of disease data. It was found that a model which allows for expansion in health infrastructure yields nearly 40% more total DALYs for a hypothetical sub-Saharan African country than a model which neglects infrastructure expansion. Widespread use of cost-effectiveness databases for resource allocations in the health sector will require the cost-effectiveness analyses shift from reporting costs to reporting production functions. Second, three distinct policy questions can be treated using these tools, each necessitating its own inputs and constraints: allocations when given a fixed budget and health infrastructure, or when given resources for marginal expansion, or when given a politically constrained situation of expanding resources. Confusion concerning which question is being addressed must be avoided through development of a consistent and rigorous approach to using cost-effectiveness data for informing resource allocations.

Computer Simulation↗
PubMed1994

Quantifying the burden of disease: the technical basis for disability-adjusted life years.

Detailed assumptions used in constructing a new indicator of the burden of disease, the disability-adjusted life year (DALY), are presented. Four key social choices in any indicator of the burden of disease are carefully reviewed. First, the advantages and disadvantages of various methods of calculating the duration of life lost due to a death at each age are discussed. DALYs use a standard expected-life lost based on model life-table West Level 26. Second, the value of time lived at different ages is captured in DALYs using an exponential function which reflects the dependence of the young and the elderly on adults. Third, the time lived with a disability is made comparable with the time lost due to premature mortality by defining six classes of disability severity. Assigned to each class is a severity weight between 0 and 1. Finally, a three percent discount rate is used in the calculation of DALYs. The formula for calculating DALYs based on these assumptions is provided.

Adolescent↗
PubMed1994

Global and regional cause-of-death patterns in 1990.

Demographic estimation techniques suggest that worldwide about 50 million deaths occur each year, of which about 39 million are in the developing countries. In countries with adequate registration of vital statistics, the age at death and the cause can be reliably determined. Only about 30-35% of all deaths are captured by vital registration (excluding sample registration schemes); for the remainder, cause-of-death estimation procedures are required. Indirect methods which model the cause-of-death structure as a function of the level of mortality can provide reasonable estimates for broad cause-of-death groups. Such methods are generally unreliable for more specific causes. In this case, estimates can be constructed from community-level mortality surveillance systems or from epidemiological evidence on specific diseases. Some check on the plausibility of the estimates is possible in view of the hierarchical structure of cause-of-death lists and the well-known age-specific patterns of diseases and injuries. The results of applying these methods to estimate the cause of death for over 120 diseases or injuries, by age, sex and region, are described. The estimates have been derived in order to calculate the years of life lost due to premature death, one of the two components of overall disability-adjusted life years (DALYs) calculated for the 1993 World development report. Previous attempts at cause-of-death estimation have been limited to a few diseases only, with little age-specific detail. The estimates reported in detail here should serve as a useful reference for further public health research to support the determination of health sector priorities.

Adolescent↗
PubMed1994

Quantifying disability: data, methods and results.

Conventional methods for collecting, analysing and disseminating data and information on disability in populations have relied on cross-sectional censuses and surveys which measure prevalence in a given period. While this may be relevant for defining the extent and demographic pattern of disabilities in a population, and thus indicating the need for rehabilitative services, prevention requires detailed information on the underlying diseases and injuries that cause disabilities. The Global Burden of Disease methodology described in this paper provides a mechanism for quantifying the health consequences of the years of life lived with disabilities by first estimating the age-sex-specific incidence rates of underlying conditions, and then mapping these to a single disability index which collectively reflects the probability of progressing to a disability, the duration of life lived with the disability, and the approximate severity of the disability in terms of activity restriction. Detailed estimates of the number of disability-adjusted life years (DALYs) lived are provided in this paper, for eight geographical regions. The results should be useful to those concerned with planning health services for the disabled and, more particularly, with determining policies to prevent the underlying conditions which give rise to serious disabling sequelae.

Adolescent↗
PubMed1994

The global burden of disease in 1990: summary results, sensitivity analysis and future directions.

A basic requirement for evaluating the cost-effectiveness of health interventions is a comprehensive assessment of the amount of ill health (premature death and disability) attributable to specific diseases and injuries. A new indicator, the number of disability-adjusted life years (DALYs), was developed to assess the burden of disease and injury in 1990 for over 100 causes by age, sex and region. The DALY concept provides an integrative, comprehensive methodology to capture the entire amount of ill health which will, on average, be incurred during one's lifetime because of new cases of disease and injury in 1990. It differs in many respects from previous attempts at global and regional health situation assessment which have typically been much less comprehensive in scope, less detailed, and limited to a handful of causes. This paper summarizes the DALY estimates for 1990 by cause, age, sex and region. For the first time, those responsible for deciding priorities in the health sector have access to a disaggregated set of estimates which, in addition to facilitating cost-effectiveness analysis, can be used to monitor global and regional health progress for over a hundred conditions. The paper also shows how the estimates depend on particular values of the parameters involved in the calculation.

Adolescent↗
PubMed1993

In search of a contemporary theory for understanding mortality change.

This paper represents a speculative approach to the question of changing mortality levels in human populations. The surprising resilience and reluctance of mortality declines to respond to powerful countervailing is considered. A more integrated approach is proposed to examine the interactive roles of income, technology and behavior in relation to life expectancy. The paper concludes by a discussion of the relevance of the accumulation of health assets to national mortality levels.

Developing Countries↗
PubMed1993

Adult health: a legitimate concern for developing countries.

Adults, defined here as people between 15 and 59 years of age, in developing countries have a high risk of premature death and suffer from frequent morbidity and high rates of chronic impairment. Their ill health imposes a major burden on health services and large negative consequences on families, communities, and societies. This paper describes the level and impact of adult mortality and morbidity, and highlights some of its characteristics and causes, which in some cases contradict commonly held beliefs. It concludes that "adult health" is a legitimate public health concern for developing countries that is not being addressed. An agenda for remedial research and action is proposed.

Adolescent↗
PubMed1992

Tuberculosis: commentary on a reemergent killer.

Tuberculosis remains the leading cause of death in the world from a single infectious disease, although there is little knowledge of the mechanisms of its pathogenesis and protection from it. After a century of decline in the United States, tuberculosis is increasing, and strains resistant to multiple antibiotics have emerged. This excess of cases is attributable to changes in the social structure in cities, the human immunodeficiency virus epidemic, and a failure in certain major cities to improve public treatment programs. The economic costs of not adequately addressing the problem of tuberculosis in this country are estimated from an epidemiological model.

Acquired Immunodeficiency Syndrome↗