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M McKee

Publications and source records attributed to M McKee.

At least 19 recordsLinked to original sources
PubMed2007

The normal kidney filters nephrotic levels of albumin retrieved by proximal tubule cells: retrieval is disrupted in nephrotic states.

The origin of albuminuria remains controversial owing to difficulties in quantifying the actual amount of albumin filtered by the kidney. Here we use fluorescently labeled albumin, together with the powerful technique of intravital 2-photon microscopy to show that renal albumin filtration in non-proteinuric rats is approximately 50 times greater than previously measured and is followed by rapid endocytosis into proximal tubule cells (PTCs). The endocytosed albumin appears to undergo transcytosis in large vesicles (500 nm in diameter), identified by immunogold staining of endogenous albumin by electron microscopy, to the basolateral membrane where the albumin is disgorged back to the peritubular blood supply. In nephrotic rats, the rate of uptake of albumin by the proximal tubule (PT) is decreased. This is consistent with reduced expression of clathrin, megalin, and vacuolar H(+)-ATPase A subunit, proteins that are critical components of the PT endocytotic machinery. These findings strongly support the paradigm-shifting concept that the glomerular filter normally leaks albumin at nephrotic levels. Albuminuria does not occur as this filtered albumin load is avidly bound and retrieved by PTCs. Dysfunction of this retrieval pathway leads to albuminuria. Thus, restoration of the defective endocytotic and processing function of PT epithelial cells might represent an effective strategy to limit urinary albumin loss, at least in some types of nephrotic syndrome.

Albumins↗
PubMed2006

Access to water in the countries of the former Soviet Union.

BACKGROUND: During the Soviet period, authorities in the USSR invested heavily in collective farming and modernization of living conditions in rural areas. However, many problems remained, including poor access to many basic amenities such as water. Since then, the situation is likely to have changed; economic decline has coincided with migration and widening social inequalities, potentially increasing disparities within and between countries. AIM: To examine access to water and sanitation and its determinants in urban and rural areas of eight former Soviet countries. METHODS: A series of nationally representative surveys in Armenia, Belarus, Georgia, Moldova, Kazakhstan, Kyrgyzstan, Russia and Ukraine was undertaken in 2001, covering 18,428 individuals (aged 18+ years). RESULTS: The percentage of respondents living in rural areas varied between 27 and 59% among countries. There are wide urban-rural differences in access to amenities. Even in urban areas, only about 90% of respondents had access to cold running water in their home (60% in Kyrgyzstan). In rural areas, less than one-third had cold running water in their homes (44% in Russia, under 10% in Kyrgyzstan and Moldova). Between one-third and one-half of rural respondents in some countries (such as Belarus, Kazakhstan and Moldova) obtained their water from wells and similar sources. Access to hot running water inside the homes was an exception in rural households, reflecting the lack of modern heating methods in villages. Similarly, indoor access to toilets is common in urban areas but rare in rural areas. Access to all amenities was better in Russia compared with elsewhere in the region. Indoor access to cold water was significantly more common among rural residents living in apartments, and in settlements served by asphalt roads rather than dirt roads. People with more assets or income and living with other people were significantly more likely to have water on tap. In addition, people who had moved in more recently were more likely to have an indoor water supply. CONCLUSIONS: This was the largest single study of its kind undertaken in this region, and demonstrates that a significant number of people living in rural parts of the former Soviet Union do not have indoor access to running water and sanitation. There are significant variations among countries, with the worse situation in central Asia and the Caucasus, and the best situation in Russia. Access to water strongly correlates with socio-economic characteristics. These findings suggest a need for sustained investment in rebuilding basic infrastructure in the region, and monitoring the impact of living conditions on health.

Adolescent↗
PubMed2006

Changes in smoking prevalence in Russia, 1996-2004.

OBJECTIVES: In Russia, smoking prevalence has historically been high in men and relatively low in women. Female smoking prevalence is predicted to rise but assessment of changes has been limited by the lack of comparable data. Changes in the prevalence of smoking in Russia between 1996 and 2004, and whether theses changes differed by sociodemographic groups, were investigated. DESIGN: Repeated national interview surveys in 1996 (731 men and 868 women) and 2004 (727 men and 864 women) aged 18 years or more. MAIN OUTCOME MEASURE: Prevalence of current smoking. RESULTS: The age standardised prevalence of smoking in 1996 and 2004 was 61% and 63%, respectively in men and 15% and 16%, respectively in women (both p values > 0.4). In men, the prevalence of smoking seemed to decline in those with university education (from 51% to 40%, p = 0.085). Among women, smoking appeared to increase in those with university education (from 10% to 17%, p = 0.071) and low levels of self-reported material deprivation (from 11% to 18%, p = 0.053). There was a pronounced increase in prevalence among women living in villages (from 8% to 14%, p = 0.049); the strong urban/rural gradient seen in 1996 became considerably weaker by 2004. CONCLUSIONS: Overall smoking prevalence in both men and women in Russia remained stable between 1996 and 2004 but, given the sample size, a moderate increase in female smoking cannot be ruled out. In men, smoking increased among the least educated and declined in the most educated. In women the opposite appeared to occur, in addition to an increase in smoking in rural areas. More long term monitoring of smoking patterns in Russia, especially among women, using sufficiently large surveys, is required.

Adolescent↗
PubMed2005

Distinct expression patterns of different subunit isoforms of the V-ATPase in the rat epididymis.

In the epididymis and vas deferens, the vacuolar H(+)ATPase (V-ATPase), located in the apical pole of narrow and clear cells, is required to establish an acidic luminal pH. Low pH is important for the maturation of sperm and their storage in a quiescent state. The V-ATPase also participates in the acidification of intracellular organelles. The V-ATPase contains many subunits, and several of these subunits have multiple isoforms. So far, only subunits ATP6V1B1, ATP6V1B2, and ATP6V1E2, previously identified as B1, B2, and E subunits, have been described in the rat epididymis. Here, we report the localization of V-ATPase subunit isoforms ATP6V1A, ATP6V1C1, ATP6V1C2, ATP6V1G1, ATP6V1G3, ATP6V0A1, ATP6V0A2, ATP6V0A4, ATP6V0D1, and ATP6V0D2, previously labeled A, C1, C2, G1, G3, a1, a2, a4, d1, and d2, in epithelial cells of the rat epididymis and vas deferens. Narrow and clear cells showed a strong apical staining for all subunits, except the ATP6V0A2 isoform. Subunits ATP6V0A2 and ATP6V1A were detected in intracellular structures closely associated but not identical to the TGN of principal cells and narrow/clear cells, and subunit ATP6V0D1 was strongly expressed in the apical membrane of principal cells in the apparent absence of other V-ATPase subunits. In conclusion, more than one isoform of subunits ATP6V1C, ATP6V1G, ATP6V0A, and ATP6V0D of the V-ATPase are present in the epididymal and vas deferens epithelium. Our results confirm that narrow and clear cells are well fit for active proton secretion. In addition, the diverse functions of the V-ATPase may be established through the utilization of specific subunit isoforms. In principal cells, the ATP6V0D1 isoform may have a physiological function that is distinct from its role in proton transport via the V-ATPase complex.

Animals↗
PubMed2005

Exploring the impact of foreign direct investment on tobacco consumption in the former Soviet Union.

BACKGROUND: Tobacco is the single largest cause of morbidity and mortality in the developed world; in the former socialist bloc tobacco kills twice as many men as in the west. Although evidence shows that liberalisation of the cigarette trade through the elimination of import barriers leads to significant increases in consumption, far less is known about the impact of foreign direct investment on cigarette consumption. This paper seeks to explore the impact that the substantial transnational tobacco company investments have had on patterns of tobacco trade and consumption in the former Soviet Union. DESIGN: Routine data were used to explore trends in cigarette trade and consumption in the 15 countries of the former Soviet Union from the 1960s to the present day. Comparisons were made between trends in countries that have received substantial investment from the tobacco transnationals and countries that have not. RESULTS: Between 1991 and 2000 cigarette production increased by 96% in countries receiving industry investment and by 11% in countries that did not. Over the same period cigarette consumption increased by 40%; the increase was concentrated in countries receiving investments. Despite these investments, cigarette imports still outweigh exports and no trade surplus has yet to result. CONCLUSIONS: The findings suggest that liberalisation of inward investment has a significant and positive impact on cigarette consumption and that without appropriate safeguards, market liberalisation may have long term negative impacts on health. Specific trade rules are needed to govern trade and investment in this uniquely harmful product. Implementation of effective tobacco control policies should precede tobacco industry privatisation. International financial organisations pressing for privatisation should ensure this occurs.

Commerce↗
PubMed2005

Indirect reduction and percutaneous fixation versus open reduction and internal fixation for displaced intra-articular fractures of the distal radius: a randomised, controlled trial.

A total of 179 adult patients with displaced intra-articular fractures of the distal radius was randomised to receive indirect percutaneous reduction and external fixation (n = 88) or open reduction and internal fixation (n = 91). Patients were followed up for two years. During the first year the upper limb musculoskeletal function assessment score, the SF-36 bodily pain sub-scale score, the overall Jebsen score, pinch strength and grip strength improved significantly in all patients. There was no statistically significant difference in the radiological restoration of anatomical features or the range of movement between the groups. During the period of two years, patients who underwent indirect reduction and percutaneous fixation had a more rapid return of function and a better functional outcome than those who underwent open reduction and internal fixation, provided that the intra-articular step and gap deformity were minimised.

Adolescent↗
PubMed2004

Comparison of the Micro-Nutrica Nutritional Analysis program and the Russian Food Composition Database using data from the Baltic Nutrition Surveys.

OBJECTIVE: The objective of this study was to compare the nutrient content of foods and diets based on data from two food composition databases used in the Baltic Nutrition Surveys (conducted in Estonia, Latvia and Lithuania in 1997): an adapted version of the Finnish Micro-Nutrica Nutritional Analysis program (used in Estonia) and the Russian Institute of Nutrition Food Composition Database (used in Latvia and Lithuania). DESIGN: The adapted Micro-Nutrica and Russian databases were used to estimate the energy and nutrient (protein, fat, carbohydrate, vitamin C, calcium and iron) content of 15 common foodstuffs in the region and the nutrient intakes of 32 Latvian respondents (based on 24-h recalls). Differences between databases were estimated. RESULTS: There were discrepancies in the energy and nutrient content of the 15 selected foods using the two databases. The adapted Micro-Nutrica database generally gave a lower energy content than the Russian database (median: -6%), and a lower fat content for typically fat-rich foods. Intakes of energy, fat, carbohydrate and calcium by the 32 selected respondents were significantly lower when the Micro-Nutrica database was used. Differences were particularly high for fat (difference=-23.5%, 95% confidence interval=-31.1 to -15.8%, P<0.0001). CONCLUSIONS: The results suggest that reported comparisons of nutrient intakes in the Baltic countries should be treated with caution and that more research is needed for the development of comparable national databases in the region. Potential differences between databases should be investigated early when international surveys of dietary intake are being planned.

Baltic States↗
PubMed2004

Type 2 diabetes in Tirana City, Albania: a rapid increase in a country in transition.

AIMS: To determine how the prevalence of Type 2 diabetes mellitus has changed in Tirana, the capital of Albania, over 20 years. METHODS: Cluster sampling was used to select 700 households including 1540 adults 25 years of age and over in Tirana City, Albania in 2001. RESULTS: Of 1540 potential subjects, 1120 participated (response rate 72.7%). Using the 1985 WHO criteria to provide comparability with earlier data, the overall prevalence of Type 2 diabetes mellitus in the age group 25+ was 6.3% (95% confidence interval 4.8-7.7); 6.9% (4.8-9.1%) male; 5.6% (3.8-7.5%) female. The age-adjusted prevalence in those aged 25+ was 5.4%. Of respondents, 3.4% were known to have diabetes, and 2.9% were newly identified through the survey. The prevalence of diabetes increased with age, although among men there was a slight decline after age 65. Impaired glucose tolerance was found in a further 2.9% of respondents, again increasing with age. The prevalence of diabetes has increased significantly since 1980, doubling in the age group 50+. Use of the 1999 WHO diagnostic criteria produces a higher unadjusted prevalence, at 9.7% (8-11.4%). In a logistic regression model, obesity and family history were independent determinants of the probability of having diabetes. Among those known to have diabetes, control was poor. CONCLUSIONS: The prevalence of diabetes in Albania has increased rapidly, consistent with what has been seen in other countries undergoing rapid modernization. It is likely to increase further in the future, with important implications for health policy.

Adult↗
PubMed2004

Open fractures of the calcaneus: a review of treatment and outcome.

OBJECTIVES: The aim of this study was to evaluate the functional and clinical outcome of patients with open calcaneus fractures and to determine what factors were associated with these outcomes. DESIGN: Retrospective review of 2 level 1 prospective databases. SETTING/PATIENTS/PARTICIPANTS: All patients admitted with an open calcaneal fracture to 2 level 1 trauma units between January 1, 1987 and April 1, 1996 were identified. Data regarding demographics, injury characteristics, and treatment and complications were documented using a standardized data abstraction form. Radiographs were reviewed to document the fracture type according to Essex-Lopresti. For those patients who had computed tomography scans available, the Sanders et al classification was applied and documented. Patients were contacted and asked to return for follow-up evaluation including the American Orthopaedic Foot and Ankle Society ankle/hindfoot score, the Maryland Foot Score, and the Short Form 36 (SF-36). For patients not willing to return for examination, the questionnaires were completed over the telephone, and the objective scoring components were assigned to lowest score possible. RESULTS: Of 177 calcaneal fractures in patients treated as inpatients during the study period, we identified 30 open fractures in 29 patients. Twenty-seven patients had associated injuries. Two patients underwent amputation within 24 hours due to severe crush injury. Following urgent debridement, soft tissues were closed primarily (22 fractures) or with split thickness skin grafting (4 fractures) and free flap coverage (2 fractures); temporary spanning external fixation was used in 3 patients. Definitive fracture care was at the discretion of the treating surgeon and consisted of closed reduction without fixation (10 fractures), open reduction and bone grafting (1 fracture), minimal Kirschner wire (K wire) fixation (12 fractures), and formal lateral open reduction and internal fixation (5 fractures). There were no late amputations. There were no deep infections. Twenty-one of the 28 patients with salvaged limbs returned for follow-up evaluation, and 3 additional patients agreed to be interviewed by telephone. The average time to follow-up was 49 months with a range of 25 to 106 months. The overall American Orthopaedic Foot and Ankle Society ankle/hindfoot scores and Maryland Foot Scores were fair to poor. The average SF-36 results were within 1 standard deviation of published Canadian norms. Worse function was observed in patients with plantar wounds. Severely comminuted fractures had the worst function, whereas single joint depression injuries had the best functional outcome. CONCLUSION: Infection is uncommon following open calcaneus fractures treated with aggressive soft tissue management. Patients with plantar wounds and comminuted fractures are expected to have particularly poor functional results.

Adolescent↗
PubMed2004

Tobacco and transition: an overview of industry investments, impact and influence in the former Soviet Union.

OBJECTIVES: To quantify the contribution the tobacco industry has made to foreign direct investment (FDI) in the former Soviet Union (FSU) as an indicator of its political and economic leverage; to explore the impact this has had on production capacity and tobacco control in the region. DESIGN: Data on industry investment and its impact on cigarette production capacity were collated from industry journals, reports, and websites. Data on total FDI were obtained from the European Bank of Reconstruction and Development. RESULTS: By the end of 2000, transnational tobacco companies (TTCs) had invested over 2.7 billion US dollars in 10 countries of the FSU. Tobacco money as a proportion of FDI varies from 1% to over 30% in Uzbekistan. Cigarette production capacity in the factories receiving investments tripled from 146 to 416 billion cigarettes per annum and the TTCs' market share has increased from nothing to between 50-100% in the markets in which they invested. Findings suggest that the effectiveness of national tobacco control measures corresponds broadly to the nature of the political and economic transition in each country and the size of industry investment, which is determined in part by the political context. Thus more effective measures tend to be seen in democratic states with smaller or no industry investments while the least effective measures are seen in highly centralised, one party states with high levels of industry investment or those with limited governmental capacity. CONCLUSIONS: The entry of the TTCs at a time of major political and economic change left the FSU particularly vulnerable to industry influence. This influence was enhanced by the industry's significant contribution to FDI, their ability to take over existing state monopolies in all but the largest countries, and the lack of democratic opposition.

Advertising↗
PubMed2004

Moving East: how the transnational tobacco industry gained entry to the emerging markets of the former Soviet Union-part I: establishing cigarette imports.

OBJECTIVES: To identify British American Tobacco's (BAT) reasons for targeting the former Soviet Union following its collapse in 1991 and the initial strategies BAT used to enter the region. DESIGN: Analysis of tobacco industry documents held at the Guildford BAT archive. RESULTS: Desire to expand to new markets was based in part on the decline in old markets. The large population, proximity to China, scope to expand sales to women and, in Central Asia, a young population with high growth rates made the former Soviet Union particularly attractive. High consumption rates and unfilled demand caused by previous shortages offered potential for rapid returns on investment. A series of steps were taken to penetrate the markets with the initial focus on establishing imports. The documents suggest that BAT encouraged the use of aid money and barter trade to fund imports and directed the smuggling of cigarettes which graduated from an opportunistic strategy to a highly organised operation. In establishing a market presence, promotion of BAT's brands and corporate image were paramount, and used synonymously to promote both the cigarettes and the company. The tobacco industry targeted young people and women. It used the allure of western products to promote its brands and brand stretching and corporate imagery to pre-empt future marketing restrictions. CONCLUSIONS: BAT used the chaotic conditions in the immediate post-transition period in the former Soviet Union to exploit legislative loopholes and ensure illegal cigarette imports. Governments of countries targeted by the tobacco industry need to be aware of industry tactics and develop adequate tobacco control policies in order to prevent the exploitation of vulnerable populations. Marketing restrictions that focus on advertising without restricting the use of brand or company promotions will have a limited impact.

Advertising↗
PubMed2004

Moving East: how the transnational tobacco industry gained entry to the emerging markets of the former Soviet Union-part II: an overview of priorities and tactics used to establish a manufacturing presence.

OBJECTIVES: To explore how British American Tobacco (BAT), having established cigarette imports, responded to the opportunities for investment in cigarette manufacturing in the former Soviet Union (FSU). DESIGN: Analysis of documents held at the BAT archive in Guildford, UK. RESULTS: Considerable priority was attached to investing in the FSU. This led BAT to undertake a major organisational change and to intense competition to acquire assets. BAT used flawed economic arguments to persuade cash starved governments that its investment would reap economic rewards. It offered excise advice that disadvantaged governments while benefiting BAT, confused issues over pricing, and avoided competitive tendering. BAT targeted agriculture ministries, using its expertise in leaf production to differentiate itself from other potential investors. It subverted the principles of corporate social responsibility to promote itself as a business partner. BAT's task was made easier by the naivety of post-Soviet governments and by the international financial organisations' support for rapid economic reform. The latter permitted tobacco transnationals to penetrate markets before effective competitive tendering processes had been established, giving them the opportunity to minimise prices and establish monopolies. CONCLUSIONS: Many of the arguments employed when penetrating post-Soviet markets were highly misleading but governments lacked expertise to realise this. There is a need to build tobacco control capacity in transition economies, within and outside government, to ensure that governments are better informed of the true economic and health impacts of tobacco. Rapid transition from socialist to market economies without establishing regulatory institutional structures may be dangerous when investing companies use business practices that fall short of international standards.

Advertising↗
PubMed2004

Health systems in transition in Central and Eastern Europe.

On 1 May 2004, eight former communist countries of Central and Eastern Europe joined the European Union (EU). THis created a range of challenges for health policy in the new member states. On top of issues relating to the health of their populations, their economic situation, and the changing nature of healthcare that affects all countries, the process of acceding to the EU requires them to adhere to the accumulated boyd of European law, some of which has implications, directly or indirectly, for health policy. This paper examines these challenges and the responses being developed to them. While the countries have much in common, in particular the shift from the former model of healthcare financing to a more pluralistic model, often based on health insurance, there is also considerable diversity, as each is using different policy options to achieve the same broad objectives. While these countries have much in common, not least the experience of EU accession, they also have considerable flexibility to pursue the systems that they choose. The challenge is to enable a process of homogenous model that ignores their important systems of healthcare being adopted by their neighbours in this region and to the models existing in the countries of Western Europe, but instead should be looking to the systems that they will have to put in place to meet the specific health needs of their own populations, which are different from those in other parts of Europe as well to meet the challenges of the future.

Delivery of Health Care↗
PubMed2003

Epidemiology of hypertension and associated cardiovascular risk factors in a country in transition: a population based survey in Tirana City, Albania.

STUDY OBJECTIVE: To describe the prevalence of hypertension and other cardiovascular risk factors on the adult population of Tirana City (Albania). DESIGN: Cross sectional survey. SETTING: Tirana City in mid-2001. PARTICIPANTS: 1120 adults aged 25 years and over (response rate=72.7%). MAIN RESULTS: Overall, hypertension prevalence (blood pressure =140 and/or 90 mm Hg, or known hypertensive receiving anti-hypertensive treatment) was 31.8% (36.6% and 27.4% in men and women respectively). Age standardised prevalence of hypertension (adjusted to the adult population of Tirana) was 30.2% (99% confidence intervals 29.8% to 30.6%) in men and 22.7% (22.3% to 23.1%) in women. Men were significantly more likely to be hypertensive than women (p value=0.001). Of those who had been diagnosed with hypertension, 87% were receiving anti-hypertensive therapy and more than half of them (52%) were adequately controlled. The prevalence of hypertension increased with increasing age and was more common in the obese in both sexes. While the prevalence of hypertension matched that in other industrialised and transition countries, the combination of hypertension with other cardiovascular risk factors was rather less common. CONCLUSION: These findings provide important new evidence on the prevalence of hypertension and its association with other cardiovascular risk factors in Albania. Albania is in a state of rapid transition, with evidence that risk factors for non-communicable diseases have already increased considerably over the past two decades. These finding provide a unique baseline against which future change can be compared.

Adult↗
PubMed2002

Is the link between alcohol and cardiovascular death among young Russian men attributable to misclassification of acute alcohol intoxication? Evidence from the city of Izhevsk.

BACKGROUND: Research on the aetiology of sudden cardiac death among young men in Russia strongly suggests an association with binge drinking. However, the possibility remains that such deaths are misclassified as being attributable to cardiovascular disease when they are really caused by acute alcohol poisoning. OBJECTIVE: To describe postmortem levels of blood alcohol in Russian men dying from various causes and so determine whether deaths from alcohol poisoning are being misclassified as cardiovascular deaths. SETTING: Ishevsk, capital of the Udmurt Republic, situated in the Ural region of the Russian Federation. METHODS: The study was part of a larger one on adult mortality. The study sample was 309 deaths among men aged 20-55 dying between August 1998 and March 1999 from other than neoplasms, infectious diseases or unspecified causes and on whom necropsy records could be obtained. Information on cause of death was extracted from death certificates and data on postmortem blood alcohol concentration (BAC) from forensic records. Blood alcohol concentrations were adjusted where necessary to allow for delay in necropsy. RESULTS: Medium or greater levels of intoxication occurred in a quarter of those recorded as dying from cardiovascular disease but in over half of those dying from external causes. BAC levels consistent with at least strong intoxication were seen in 13.5% of deaths from cardiovascular disease and 27.1% from external causes. No cardiovascular deaths had BAC at levels usually thought to be fatal while this level was seen in 26% of deaths from accidental poisoning. CONCLUSION: Evidence of recent consumption of alcohol is common among Russian men dying under the age of 55, with severe intoxication common where death is from external causes. However, the high death rates from cardiovascular disease in Russia cannot be explained by misclassification of deaths attributable to acute alcohol poisoning. This study thus resolves one of the outstanding controversies in the story of alcohol and cardiovascular disease in the former Soviet Union.

Adult↗
PubMed2002

Changing life expectancy in Romania after the transition.

BACKGROUND: While Poland, Hungary, and the Czech Republic have seen impressive gains in life expectancy in the 1990s, Romania has not. In contrast with the other countries, there has been very little research on the causes of the pattern of mortality seen in Romania. OBJECTIVES: To describe the trends in life expectancy at birth in Romania after the political transition in 1989 and to evaluate the contribution of deaths from different causes and different ages to these changes. METHODS: Decomposition of life expectancy by age and cause of death using routine data on mortality for the years 1990, 1996, and 1998; comparison of death rates by age, sex, and cause of death. RESULTS: Romania has experienced an overall decline of 1.71 years of life expectancy at birth from 1990 to 1996 in men and 0.54 years in women. The major contribution to this decline was an increase in mortality from cardiovascular diseases and diseases of the digestive system, in particular cirrhosis, among the middle aged and elderly. The recovery observed in 1998, of 1.12 years in men and 0.89 years in women, was mainly caused by a reduction in deaths from cardiovascular disease in the middle aged and elderly. Infant and early childhood mortality fell throughout the period but there was an increase of approximately 40% in mortality at age 5-9 that was almost entirely attributable to AIDS. CONCLUSION: This is the first Romanian study that describes the evolution of life expectancy after transition. Romania may at last be beginning to follow the path of improving adult mortality seen in the early 1990s in some of its neighbours. It has, however, been unique in eastern Europe in experiencing increasing childhood mortality. This is attributable to an epidemic of paediatric AIDS, consequent on the tragically inappropriate policies adopted in the 1980s.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Refined crystallographic structure of Pseudomonas aeruginosa exotoxin A and its implications for the molecular mechanism of toxicity.

Exotoxin A of Pseudomonas aeruginosa asserts its cellular toxicity through ADP-ribosylation of translation elongation factor 2, predicated on binding to specific cell surface receptors and intracellular trafficking via a complex pathway that ultimately results in translocation of an enzymatic activity into the cytoplasm. In early work, the crystallographic structure of exotoxin A was determined to 3.0 A resolution, revealing a tertiary fold having three distinct structural domains; subsequent work has shown that the domains are individually responsible for the receptor binding (domain I), transmembrane targeting (domain II), and ADP-ribosyl transferase (domain III) activities, respectively. Here, we report the structures of wild-type and W281A mutant toxin proteins at pH 8.0, refined with data to 1.62 A and 1.45 A resolution, respectively. The refined models clarify several ionic interactions within structural domains I and II that may modulate an obligatory conformational change that is induced by low pH. Proteolytic cleavage by furin is also obligatory for toxicity; the W281A mutant protein is substantially more susceptible to cleavage than the wild-type toxin. The tertiary structures of the furin cleavage sites of the wild-type and W281 mutant toxins are similar; however, the mutant toxin has significantly higher B-factors around the cleavage site, suggesting that the greater susceptibility to furin cleavage is due to increased local disorder/flexibility at the site, rather than to differences in static tertiary structure. Comparison of the refined structures of full-length toxin, which lacks ADP-ribosyl transferase activity, to that of the enzymatic domain alone reveals a salt bridge between Arg467 of the catalytic domain and Glu348 of domain II that restrains the substrate binding cleft in a conformation that precludes NAD+ binding. The refined structures of exotoxin A provide precise models for the design and interpretation of further studies of the mechanism of intoxication.

ADP Ribose Transferases↗