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Biomedical subjects

D A Stone

Publications and source records attributed to D A Stone.

At least 19 recordsLinked to original sources
PubMed2004

Human contribution to the European heatwave of 2003.

The summer of 2003 was probably the hottest in Europe since at latest ad 1500, and unusually large numbers of heat-related deaths were reported in France, Germany and Italy. It is an ill-posed question whether the 2003 heatwave was caused, in a simple deterministic sense, by a modification of the external influences on climate--for example, increasing concentrations of greenhouse gases in the atmosphere--because almost any such weather event might have occurred by chance in an unmodified climate. However, it is possible to estimate by how much human activities may have increased the risk of the occurrence of such a heatwave. Here we use this conceptual framework to estimate the contribution of human-induced increases in atmospheric concentrations of greenhouse gases and other pollutants to the risk of the occurrence of unusually high mean summer temperatures throughout a large region of continental Europe. Using a threshold for mean summer temperature that was exceeded in 2003, but in no other year since the start of the instrumental record in 1851, we estimate it is very likely (confidence level >90%) that human influence has at least doubled the risk of a heatwave exceeding this threshold magnitude.

Air Pollution↗
PubMed2001

Quantifying the ion selectivity of the Ca2+ site in photosystem II: evidence for direct involvement of Ca2+ in O2 formation.

Calcium is an essential cofactor in the oxygen-evolving complex (OEC) of photosystem II (PSII). The removal of Ca2+ or its substitution by any metal ion except Sr2+ inhibits oxygen evolution. We used steady-state enzyme kinetics to measure the rate of O2 evolution in PSII samples treated with an extensive series of mono-, di-, and trivalent metal ions in order to determine the basis for the affinity of metal ions for the Ca2+-binding site. Our results show that the Ca2+-binding site in PSII behaves very similarly to the Ca2+-binding sites in other proteins, and we discuss the implications this has for the structure of the site in PSII. Activity measurements as a function of time show that the binding site achieves equilibrium in 4 h for all of the PSII samples investigated. The binding affinities of the metal ions are modulated by the 17 and 23 kDa extrinsic polypeptides; their removal decreases the free energy of binding of the metal ions by 2.5 kcal/mol, but does not significantly change the time required to reach equilibrium. Monovalent ions are effectively excluded from the Ca2+-binding site, exhibiting no inhibition of O2 evolution. Di- and trivalent metal ions with ionic radii similar to that of Ca2+ (0.99 A) bind competitively with Ca2+ and have the highest binding affinity, while smaller metal ions bind more weakly and much larger ones do not bind competitively. This is consistent with a size-selective Ca2+-binding site that has a rigid array of coordinating ligands. Despite the large number of metal ions that competitively replace Ca2+ in the OEC, only Sr2+ is capable of partially restoring activity. Comparing the physical characteristics of the metal ions studied, we identify the pK(a) of the aqua ion as the factor that determines the functional competence of the metal ion. This suggests that Ca2+ is directly involved in the chemistry of water oxidation and is not only a structural cofactor in the OEC. We propose that the role of Ca2+ is to act as a Lewis acid, binding a substrate water molecule and tuning its reactivity.

Binding, Competitive↗
PubMed2000

Do medical devices have enhanced placebo effects?

Although the placebo in a clinical trial is often considered simply a baseline against which to evaluate the efficacy of a clinical intervention, there is evidence that the magnitude of placebo effect may be a critical factor in determining the results of a trial. This article examines the question of whether devices have enhanced placebo effects and, if so, what the implications may be. While the evidence of an enhanced placebo effect remains rudimentary, it is provocative and therefore worthy of further study. Suggestions are made, therefore, for how such an effect can be investigated without violating the principles of informed consent.

Clinical Trials as Topic↗
PubMed2000

United States.

Explore the source record for details and available documents.

Financing, Organized↗
PubMed2000

The value of case management in the publicly funded substance abuse treatment system. The perspective of program directors, case managers and clients.

The many purposes of this article is to understand the role and value of case management from the perspective of program directors, case managers and clients. A survey of program directors from publicly funded substance abuse treatment programs in Boston was administered, and in-depth interviews with a sample of program directors, case managers, and clients were conducted. Case management allowed programs to serve more complex clients and increased time available for counselors to focus on the clinical needs of clients. From the perspective of case managers and clients, much of the value of case management came from educating clients about steps they could take to meet their needs and then supporting them in their efforts as they took these steps. Successful steps taken to deal with these needs helped lay the foundation necessary to confront the challenges of treatment. Program directors, case managers, and clients considered case management a valuable enhancement to substance abuse treatment.

Attitude of Health Personnel↗
PubMed1999

Metabolic engineering of Arabidopsis and Brassica for poly(3-hydroxybutyrate-co-3-hydroxyvalerate) copolymer production.

Poly(hydroxyalkanoates) are natural polymers with thermoplastic properties. One polymer of this class with commercial applicability, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) can be produced by bacterial fermentation, but the process is not economically competitive with polymer production from petrochemicals. Poly(hydroxyalkanoate) production in green plants promises much lower costs, but producing copolymer with the appropriate monomer composition is problematic. In this study, we have engineered Arabidopsis and Brassica to produce PHBV in leaves and seeds, respectively, by redirecting the metabolic flow of intermediates from fatty acid and amino acid biosynthesis. We present a pathway for the biosynthesis of PHBV in plant plastids, and also report copolymer production, metabolic intermediate analyses, and pathway dynamics.

Acyl Coenzyme A↗
PubMed1999

Comparing pediatric intentional injury surveillance data with data from publicly available sources: consequences for a public health response to violence.

OBJECTIVE: A hospital based intentional injury surveillance system for youth (aged 3-18) was compared with other publicly available sources of information on youth violence. The comparison addressed whether locally conducted surveillance provides data that are sufficiently more complete, detailed, and timely that clinicians and public health practitioners interested in youth violence prevention would find surveillance worth conducting. SETTING: The Boston Emergency Department Surveillance (BEDS) project was conducted at Boston Medical Center and the Children's Hospital, Boston. METHOD: MEDLINE and other databases were searched for data sources that report separate data for youth and data on intentional injury. Sources that met these criteria (one national and three local) were then compared with BEDS data. Comparisons were made in the following categories: age, gender, victim-offender relationship, injury circumstance, geographic location, weapon rates, and violent injury rates. RESULTS: Of 14 sources dealing with violence, only four met inclusion criteria. Each source provided useful breakdowns for age and gender; however, only the BEDS data were able to demonstrate that 32.6% of intentional injuries occurred among youth aged 12 and under. Comparison data sources provided less detail regarding the victim-offender relationship, injury circumstance, and weapon use. Comparison of violent injury rates showed the difficulties for practitioners estimating intentional injury from sources based on arrest data, crime victim data, or weapon related injury. CONCLUSIONS: Comparison suggests that surveillance is more complete, detailed, and timely than publicly available sources of data. Clinicians and public health practitioners should consider developing similar systems.

Adolescent↗
PubMed1997

The doctor as businessman: the changing politics of a cultural icon.

From just after the Civil War, when medicine began to professionalize, until the late 1970s, doctors and policy makers believed that clinical judgment should not be influenced by the financial interests of doctors. Physicians were highly entrepreneurial, and organized medicine fought to preserve their entrepreneurial interests, but the moral norm that justified their autonomy from state regulation was a strict separation of clinical judgment and pecuniary interests. Under managed care, the old norm is reversed. A good doctor takes financial considerations into account in making clinical decisions. Theoretically, doctors should consider measures of cost to society, but in practice, the payment systems of managed care plans induce doctors to consider the impact of each clinical decision on their own income. Because doctors share the risks of insuring patients with managed care plans, they have the same incentives as insurers to avoid patients who are expensively sick. The new cultural image of doctors as entrepreneurs masks their considerable loss of clinical autonomy under managed care. It also serves to persuade doctors to accept managed care arrangements and to persuade insurance consumers and patients to accept reduced benefits from employers and the government.

Commerce↗
PubMed1997

A peptidomimetic that specifically inhibits human leukocyte antigen DRB1*0401-restricted T cell proliferation.

The ability of a peptidomimetic (SC-67655) to block the peptide binding site of the rheumatoid arthritis-linked human leukocyte antigen encoded by the DRB1*0401 allele was evaluated. The inhibitor bound to purified DRB1*0401 molecules with an affinity similar to that of the well-characterized peptide ligand HA307-319. Cell binding assays demonstrated that, in contrast to the promiscuous HA307-319 peptide, the peptidomimetic was highly specific for DRB1*0401. The inhibitor also blocked functional T cell responses to peptide antigens but did not block T cell proliferation in response to protein antigens. Furthermore, it did not appear to be taken up by cells. An analog of the peptidomimetic that was conjugated to a signal peptide sequence did inhibit a T cell proliferative response to protein antigen. Thus, the peptidomimetic must be taken up by cells to block the presentation of peptides derived from protein antigens. These findings have implications for the rational development of inhibitors that block the class II peptide binding groove for the treatment of autoimmune diseases.

Binding Sites↗
PubMed1996

Preoperative cardiac risk assessment with adenosine stress dual-isotope myocardial single-photon emission computed tomography.

BACKGROUND: Previous studies have demonstrated that pharmacologic stress thallium-201 (201Tl) myocardial scintigraphy is a useful tool to evaluate preoperative cardiac risk. HYPOTHESIS: The purpose of this study was to assess the utility of adenosine stress dual-isotope [rest 201Tl/stress technetium-99m (99mTc) sestamibi] myocardial single-photon emission computed tomography (SPECT) in predicting the risk of perioperative cardiac events (unstable angina, myocardial infarction, cardiac death) in patients undergoing major noncardiac surgery. METHODS: We evaluated 43 consecutive patients (20 men, 23 women, mean age 64 years, range 30-83 years) within 8 weeks prior to major noncardiac surgery requiring general anesthesia. SPECT imaging was performed with 111 MBq (3 mCi) 201Tl at rest and 925 MBq (25 mCi)99mTc sestamibi during adenosine stress. RESULTS: Of the 43 patients, 15 (35%) had stress-induced ischemia and 28 (65%) did not. Perioperative cardiac events occurred in 4 (27%) of the 15 patients with stress-induced ischemia (2 unstable angina, 2 nonfatal myocardial infarctions) and in none of the 28 patients without inducible ischemia (p = 0.02). CONCLUSION: Adenosine stress dual-isotope myocardial SPECT is useful in determining the preoperative cardiac risk of patients undergoing major noncardiac surgery.

Adenosine↗
PubMed1996

The experience of violent injury for young African-American men: the meaning of being a "sucker".

OBJECTIVE: To explore the experience of violent injury among young African-American men with gunshot or stab wounds to better understand violent injury. DESIGN: Convenience sample, using open-ended, semistructured interviews. SETTING: An urban, municipal hospital in Boston. PATIENTS: Eighteen African-American men between the ages of 18 and 25, who had been shot or stabbed. RESULTS: Analysis of the interviews revealed that these young men identify with a concept called "being a sucker". They perceive that a person who fails to retaliate when he is disrespected or injured will be viewed as weak and will be the target of future victimization. CONCLUSIONS: This study reveals an important perception among these young male victims of violence that if they fail to respond violently to injury or the threat of injury, they will be at risk of further victimization. The social environment in which young male victims of violence live and the meaning of being a sucker must be considered in efforts to decrease recurrent interpersonal violence. Providers who care for young men who are victims of or at risk of violence should understand the implications of the social context on individual behaviors.

Adult↗
PubMed1996

Patent foramen ovale: association between the degree of shunt by contrast transesophageal echocardiography and the risk of future ischemic neurologic events.

This study investigated whether there is an association between the degree of interatrial shunting across a patent foramen ovale, as determined by saline contrast transesophageal echocardiography, and the risk of subsequent systemic embolic events, including stroke. Thirty-four patients found to have foramen ovale during transesophageal echocardiography were divided into two groups on the basis of the maximum number of microbubbles in the left heart in any single frame after intravenous saline contrast injection: group 1 (n = 16) with a "large" degree of shunt ( > or = 20 microbubbles) and group 2 (n = 18) with a "small" degree of shunt ( > or = 3 microbubbles). Patients were followed up over a mean period of 21 months for subsequent systemic embolic events, including transient ischemic attack and stroke. Five (31%) of the patients with large shunts had subsequent ischemic neurologic events, whereas none of the patients with small shunts had embolic events (p = 0.03). These events occurred in spite of antiplatelet or anticoagulant therapy. We conclude that patients with a large degree of shunt across a patient foramen ovale, as determined by contrast transesophageal echocardiography, are at a significantly higher risk of subsequent adverse neurologic events compared with patients with a small degree of shunt.

Anticoagulants↗
PubMed1996

Agreement between rectal and tympanic membrane temperatures in marathon runners.

STUDY OBJECTIVE: To determine the agreement between rectal temperature and infrared tympanic membrane temperatures in marathon runners presenting to a field hospital at the finish line. METHODS: The subjects of this prospective, blinded, controlled study were runners 18 years or older who were triaged to the acute care medical area at the finish line for suspected hypothermia, hyperthermia, dehydration, or altered mental status. Rectal and tympanic temperatures were measured simultaneously in all subjects for whom rectal temperature measurement had been deemed necessary and recorded on separate data cards. RESULTS: Of the 239 runners treated in the acute care medical area, 37 required rectal temperature measurement and were enrolled in the study. The mean rectal temperature was 38.45 degrees +/- 1.20 degrees C (range, 35.9 degrees to 41.5 degrees C). The mean tympanic membrane temperature was 37.81 degrees +/- 95 degrees C (range, 36.3 degrees to 40.4 degrees C). Pearson's correlation coefficient revealed a moderate correlation (r = .6902, P = .00023). The mean temperature difference between the two thermometers, mean rectal minus mean tympanic membrane, was .64 degrees C (95% confidence interval, .35 degrees to .93 degrees C). Sixty-Two percent of the tympanic membrane readings were within 1 degree C of their rectal counterparts. Agreement ranged from 1.16 degrees (+2 SD) to -2.95 degrees (-2 SD). The 95% confidence interval was 1.67 degrees to -2.95 degrees C. CONCLUSION: We were able to demonstrate only a moderate correlation between the two thermometer readings, with a wide spread between the limits of agreement. This spread could be clinically significant and therefore limits the usefulness of tympanic temperature in the marathon race setting. Because of the potentially large and clinically significant differences in rectal and tympanic temperatures and the limitations inherent in our study, we cannot endorse the use of tympanic temperature in the setting of a marathon event.

Body Temperature↗
PubMed1996

Analysis of malignancy detected by needle-localized breast biopsy.

The medical records of 192 women with nonpalpable mammographically detected breast lesions who underwent needle-localized breast biopsy between January 1989 and January 1991 and between March 1992 and March 1994 were reviewed. Of the 192 patients examined, 100 underwent biopsy for evaluation of microcalcifications suggestive of malignancy. Ninety-two biopsies were performed for non-specific radiodensities not inclusive of microcalcifications. This study examines the radiographic characteristics of the nonpalpable breast lesion. Although presence of microcalcifications on mammograms are an important finding in detection of breast carcinoma, it must not be considered pathognomonic. Other distinguishing factors require evaluation to assess the indication for biopsy. Central to this study was the presence of microcalcifications alone or as detected in association with a dominant mass. Cancer was discriminated in 38 (20%) of the patients studied. Mammographic findings with microcalcification, regardless of the presence of a mass, were found to be malignant in 20% of patients undergoing biopsy. Nine percent of biopsies done to evaluate microcalcifications alone were malignant. The finding of microcalcification associated with a dominant mass proved malignant in 34% of patients who had a biopsy done. The authors include guidelines for increasing the effectiveness of needle-localized biopsies of the breast.

Adult↗
PubMed1995

The influence of angiographically demonstrated coronary collaterals on the results of stress echocardiography.

Previous studies using thallium-201 scintigraphy have suggested that angiographic coronary collaterals can protect against the development of stress-induced perfusion abnormalities, but the effect of collaterals on stress echocardiography (SECHO) has not been determined. In this study, 21 consecutive patients referred for cardiac catheterization underwent SECHO and coronary angiography. Of the 21 study patients, there was a total of 16 significantly obstructed coronary arteries (> or = 70% stenosis) in 14 patients. SECHO revealed stress-induced wall motion abnormalities in the distribution of seven of nine obstructed coronary vessels without angiographic collaterals, but in only one of seven vessels with collaterals (p < 0.05). Six of eight obstructed vessels not associated with a stress-induced wall motion abnormality had collaterals, whereas only one of eight obstructed vessels associated with a stress-induced wall motion abnormality had collaterals. We conclude that (1) angiographically demonstrated coronary collaterals can protect against the development of stress-induced wall motion abnormalities despite the presence of a high-grade coronary artery obstruction, and (2) the lack of a stress-induced wall motion abnormality on SECHO in the perfusion territory of an obstructed vessel may suggest the presence of adequate collateral perfusion.

Aged↗
PubMed1995

Ulcerated atherosclerotic plaques in the thoracic aorta are associated with cryptogenic stroke: a multiplane transesophageal echocardiographic study.

Atherosclerotic plaque ulcers > or = 2 mm in depth and width in the thoracic aorta have been implicated by autopsy study as a cause of unexplained or cryptogenic ischemic strokes. Transesophageal echocardiography (TEE) allows visualization of complex atherosclerotic lesions of the thoracic aorta. We compared the prevalence of thoracic aorta ulcerated plaques (ulcers > or = 2 mm in both depth and width) in three age-matched groups undergoing multiplane TEE: group 1, 23 patients with cryptogenic ischemic stroke; group 2, 26 patients with known-cause strokes; and group 3, 57 control patients without strokes. TEEs were interpreted in a blinded fashion. Ulcerated plaques were found in 9 (39%) group 1 patients but in only 2 (8%) group 2 patients and in only 4 (7%) group 3 patients (p < 0.001). There was an association between advancing age and the presence of ulcerated plaques (p < 0.02). We conclude that ulcerated atherosclerotic plaques in the thoracic aorta are associated with cryptogenic ischemic stroke and should be considered a potential source of cerebral emboli.

Aged↗
PubMed1995

Issues in the female athlete.

Effective treatment of the female athlete begins with an understanding of the anatomic and physiologic differences between males and females and the epidemiology of injury patterns in athletic women. However, the female athlete has a variety of special concerns that the sports medicine physician should be familiar with.

Adolescent↗