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Biomedical subjects

J Slade

Publications and source records attributed to J Slade.

At least 19 recordsLinked to original sources
PubMed2004

Mechanical environment alters tissue formation patterns during fracture repair.

Fracture repair has previously been shown to be sensitive to mechanical environment, yet the specific relationship between strain character, magnitude and frequency, as well as other mechanical parameters, and tissue formation is not well understood. This study aimed to correlate strain distribution within the healing fracture gap with patterns of tissue formation using a rat model of a healing osteotomy subject to mechanical stimulation in bending. Finite element models based on realistic tissue distributions were used to estimate both the magnitude and spatial distribution of strains within the fracture gap. The spatial distribution of regenerating tissue was determined by microcomputed tomography and histology, and was confirmed using reverse transcription-polymerase chain reaction (RT-PCR). Results suggest that tensile strains suppress chondrogenesis during the mechanical stimulation period. After stimulation ends, however, tensile strains increased chondrogenesis followed by rapid bone formation. In contrast, in compressive environments, bone is formed primarily via intramembranous ossification. Taken together, these results suggest that intermittent tensile strains during fracture repair stimulate endochondral ossification and promote eventual bone healing compared to intermittent compressive strains and unstimulated fractures. Further understanding of these relationships may allow proposal of optimal therapeutic strategies for improvement of the fracture repair process.

Animals↗
PubMed2002

Eclipse: does it live up to its health claims?

OBJECTIVE: To examine the plausibility of health claims for Eclipse, a novel smoking article being marketed by the RJ Reynolds Tobacco Company (RJR) as potentially reducing the risk of cancer and other diseases compared to conventional cigarettes. DATA SOURCES: A company product website (www.eclipse.rjrt.com) summarising scientific studies of various versions of Eclipse, and the published review of these studies by an expert panel convened by RJR, an independent study comparing the smoke yields of major carcinogens from Eclipse and two low yield "ultralight" brands (Now and Carlton), and an analysis of the levels of these compounds in Eclipse and Premier (its predecessor) over time. ANALYSIS: The overall doses and effects of toxins in the aerosol from Eclipse are smaller than those from most conventional cigarettes on a per mg basis. However, two tests that compared Eclipse on a per cigarette basis revealed that Eclipse was as or more toxic than an ultralight cigarette. Studies show that consumers smoke Eclipse (like they do cigarettes) at puff volumes and puff frequencies far higher than those used for the Federal Trade Commission (FTC) test. RJR's test results, which are based on aerosols generated under FTC conditions, may not reflect actual human dosing, since the operating temperature of Eclipse is highly dependent on these puffing parameters. Even under FTC/International Organization for Standardization (ISO) standard measures, Eclipse smoke carcinogen yields were higher than Now, but similar to Carlton. The yields of carcinogens from Premier and different versions of Eclipse have increased over time. Furthermore, the human studies reviewed by the RJR expert panel do not offer compelling evidence of reduced harm, as they have not been conducted in smokers who have adopted Eclipse. CONCLUSION: There is as yet unsatisfactory evidence that Eclipse is less harmful than conventional cigarettes. Eclipse appears to be at least as toxic as some commercially available cigarette brands. Consumers may be misled by RJR's health claims into believing that Eclipse is a safer alternative to conventional cigarettes, underscoring the need for regulatory intervention.

Advertising↗
PubMed2000

Health risks associated with cigar smoking.

This article summarizes principal findings from a conference convened by the American Cancer Society in June 1998 to examine the health risks of cigar smoking. State-of-the-science reports were presented and 120 attendees (representing government and private agencies, academia, health educators, and tobacco control experts) participated in panels and summary development discussions. The following conclusions were reached by consensus: (1) rates of cigar smoking are rising among both adults and adolescents; (2) smoking cigars instead of cigarettes does not reduce the risk of nicotine addiction; (3) as the number of cigars smoked and the amount of smoke inhaled increases, the risk of death related to cigar smoking approaches that of cigarette smoking; (4) cigar smoke contains higher concentrations of toxic and carcinogenic compounds than cigarettes and is a major source of fine-particle and carbon monoxide indoor air pollution; and (5) cigar smoking is known to cause cancers of the lung and upper aerodigestive tract. JAMA. 2000;284:735-740

Humans↗
PubMed1999

Introductory notes on the tobacco problem.

Commercial tobacco products are the leading causes of preventable death, yet they are virtually unregulated. They are popular because they are effective nicotine delivery devices, and the most addictive product (the cigarette) is also the most likely to kill.

Humans↗
PubMed1999

Effect of therapeutic hypothermia on the incidence and treatment of intracranial hypertension.

Therapeutic hypothermia initiated immediately after a severe head trauma holds promise for improving outcomes. However, the effect of hypothermia on intracranial pressure (ICP) is not yet known. This study was a secondary analysis, conducted within a National Institutes of Health clinical trial on the efficacy of therapeutic hypothermia, to determine the effects of therapeutic hypothermia on ICP and of interventions (i.e., cerebrospinal fluid drainage and mannitol administration) on intracranial hypertension. There were no significant differences in the overall incidence or treatment of intracranial hypertension between patients who were treated with therapeutic hypothermia and normal controls. Therapeutic hypothermia maintained the ICP at lower levels during the cooling phase, but once patients were rewarmed, the ICP elevated to the levels of normothermic patients.

Adolescent↗
PubMed1998

Mutation of amino acid residues in the mobile loop region of the NAD(H)-binding domain of proton-translocating transhydrogenase.

The effects of single amino acid substitutions in the mobile loop region of the recombinant NAD(H)-binding domain (dI) of transhydrogenase have been examined. The mutations lead to clear assignments of well-defined resonances in one-dimensional 1H-NMR spectra. As with the wild-type protein, addition of NADH, or higher concentrations of NAD+, led to broadening and some shifting of the well-defined resonances. With many of the mutant dI proteins more nucleotide was required for these effects than with wild-type protein. Binding constants of the mutant proteins for NADH were determined by equilibrium dialysis and, where possible, by NMR. Generally, amino acid changes in the mobile loop region gave rise to a 2-4-fold increase in the dI-nucleotide dissociation constants, but substitution of Ala236 for Gly had a 10-fold effect. The mutant dI proteins were reconstituted with dI-depleted bacterial membranes with apparent docking affinities that were indistinguishable from that of wild-type protein. In the reconstituted system, most of the mutants were more inhibited in their capacity to perform cyclic transhydrogenation (reduction of acetyl pyridine adenine dinucleotide, AcPdAD+, by NADH in the presence of NADP+) than in either the simple reduction of AcPdAD+ by NADPH, or the light-driven reduction of thio-NADP+ by NADH, which suggests that they are impaired at the hydride transfer step. A cross-peak in the 1H-1H nuclear Overhauser enhancement spectrum of a mixture of wild-type dI and NADH was assigned to an interaction between the A8 proton of the nucleotide and the betaCH3 protons of Ala236. It is proposed that, following nucleotide binding, the mobile loop folds down on to the surface of the dI protein, and that contacts, especially from Tyr235 in a Gly-Tyr-Ala motif with the adenosine moiety of the nucleotide, set the position of the nicotinamide ring of NADH close to that of NADP+ in dIII to effect direct hydride transfer.

Amino Acid Sequence↗
PubMed1998

Reducing the addictiveness of cigarettes. Council on Scientific Affairs, American Medical Association.

OBJECTIVE: To assess the feasibility of reducing tobacco-caused disease by gradually removing nicotine from cigarettes until they would not be effective causes of nicotine addiction. DATA SOURCES: Issues posed by such an approach, and potential solutions, were identified from analysis of literature published by the US Food and Drug Administration (FDA) in its 1996 Tobacco Rule, comments of the tobacco industry and other institutions and individuals on the rule, review of the reference lists of relevant journal articles, other government publications, and presentations made at scientific conferences. DATA SYNTHESIS: The role of nicotine in causing and sustaining tobacco use was evaluated to project the impact of a nicotine reduction strategy on initiation and maintenance of, and relapse to, tobacco use. A range of potential concerns and barriers was addressed, including the technical feasibility of reducing cigarette nicotine content to non-addictive levels, the possibility that compensatory smoking would reduce potential health benefits, and whether such an approach would foster illicit ("black market") tobacco sales. Education, treatment, and research needs to enable a nicotine reduction strategy were also addressed. The Council on Scientific Affairs came to the following conclusions: (a) gradually eliminating nicotine from cigarettes is technically feasible; (b) a nicotine reduction strategy holds great promise in preventing adolescent tobacco addiction and assisting the millions of current cigarette smokers in their efforts to quit using tobacco products; (c) potential problems such as compensatory over-smoking of denicotinised cigarettes and black market sales could be minimised by providing alternate forms of nicotine delivery with less or little risk to health, as part of expanded access to treatment; and (d) such a strategy would need to be accompanied by relevant research and increased efforts to educate consumers and health professionals about tobacco and health. CONCLUSIONS: The council recommends the following: (a) that cessation of tobacco use should be the goal for all tobacco users; (b) that the American Medical Association continue to support FDA authority over tobacco products, and FDA classification of nicotine as a drug and tobacco products as drug-delivery devices; (c) that research be encouraged on cigarette modifications that may result in less addicting cigarettes; (d) that the FDA require that the addictiveness of cigarettes be reduced within 5-10 years; (e) expanded surveillance to monitor trends in the use of tobacco products and other nicotine-containing products; (f) expanded access to smoking cessation treatment, and strengthening of the treatment infrastructure; and (g) more accurate labelling of tobacco products, including a more meaningful and understandable indication of nicotine content.

Behavior, Addictive↗
PubMed1997

The emerging market for long-term nicotine maintenance.

In increasing numbers, Americans will seek to satisfy nicotine addictions through the use of novel nicotine-delivery products devoid of several of the poisons that make cigarettes so deadly. In the vanguard are tobacco industry devices that heat tobacco derivatives rather than burn tobacco, and pharmaceutical industry nicotine-replacement products, with nicotine gum and the patch now available over the counter. Ostensibly, these 2 industries have diametrically opposed objectives, the tobacco industry striving to sustain nicotine addictions, the pharmaceutical industry to end them. However, a series of technological, economic, political, regulatory, and social developments augurs a strange-bedfellows competition in which these industries will vie for shares of a new multibillion dollar long-term nicotine-maintenance market. Regulatory options range from encouraging competition to banning all nicotine-delivery devices. A more realistic approach discourages use of the most dangerous products, while making less hazardous products readily available to adults.

Adult↗