Adiposity and physical activity as predictors of cardiovascular mortality.

OBJECTIVE: To investigate whether cardiovascular mortality related to obesity could be modified by physical activity. DESIGN: Mortality follow-up. SETTING: Population study. PARTICIPANTS: Participants in a health survey: 34 868 women and 32 872 men free from known cardiovascular disease or diabetes at baseline. MAIN OUTCOME MEASURES: Total cardiovascular mortality. MAIN RESULTS: During 16 years of follow-up, 3026 women and 3526 men had died from cardiovascular causes. In middle age, obesity [body mass index (BMI) of 30 or higher] was associated with increased risk of cardiovascular death, but the association weakened with age. After 70, there was no association between BMI and cardiovascular death. At all ages, a lower level of physical activity was associated with a higher cardiovascular mortality. In women with high physical activity, indicated by at least 30 min of moderate to vigorous activity more than once a week, cardiovascular mortality was only slightly higher in the obese compared to lean women (adjusted relative risk, 1.27; 95% confidence interval, 0.80-2.00). In men with high physical activity, cardiovascular mortality was, however, significantly higher among the obese (relative risk, 1.62; 95% confidence interval, 1.09-2.40). In both genders cardiovascular mortality was substantially higher in obese people who reported no regular physical activity compared to obese people with a high level of physical activity. CONCLUSION: In obese women, being highly active may, to a large extent, compensate for the risk-increasing effect of being obese, whereas in obese men who engage in a high level of physical activity, the risk of cardiovascular death may be higher than in lean and equally active men.     

Trade Herbal Products and Induction of CYP2C19 and CYP2E1 in Cultured Human Hepatocytes

Abstract: The aim of this study was to evaluate in vitro the dose‐dependent induction potential of six commonly used trade herbal products on CYP2C19 and CYP2E1 metabolic activities in cultured human hepatocytes. S‐mephenytoin and chlorzoxazone were used as specific CYP substrates, respectively, and rifampicin was used as a positive induction control for both enzymes. The hepatocytes were exposed to herbal extracts in increasing and biological relevant concentrations for 72 hrs and CYP substrate metabolites were quantified by validated HPLC methodologies. The major findings were that St John's wort was the most potent CYP‐modulating herb, showing a dose‐dependent induction/inhibition of both CYP2C19 and CYP2E1, with induction at low dosages and inhibition at higher. Ginkgo biloba showed an induction/inhibition profile towards CYP2C19 which was similar but weaker than that observed for St John's wort. If cooperative mechanisms are involved is still an open question. Common sage induced CYP2C19 in a log‐linear dose‐dependent manner with increasing concentrations. Common valerian was a weak inducer of CYP2C19, while horse chestnut and cone flower were characterized as non‐inducers of CYP2C19. Only St John's wort showed an inductive effect towards CYP2E1. In addition to St John's wort, Gingko biloba and common sage should be considered as possible candidates for clinically relevant drug‐herb interactions with selected CYP2C19 substrates.     

Tensile strength of plate osteosynthesis. Comparative biomechanical study of the original autocompression plate and a functional modification using the ZESPOL principle

In order to overcome the problems of stress protection and pressure atrophy of bone, which are associated with the traditional plating technique, in Poland a modified type of plating, ZESPOL has been, developed. In this procedure, the plate is not screwed onto the surface of the bone, but is fixed above the bone by special platform screw bolts in a comblike construction. This paper describes an experimental biomechanical investigation, using cadaver tibia, which compares the stability of the ZESPOL principle with that of the traditionally applied autocompression plate (ACP). In order to make the system biomechanically comparable, instead of the original ZESPOL plates, which are different in dimension, an ACP was used that was specially adapted to fit the ZESPOL criteria. Compared to the ACP, the bending stability of the ZESPOL osteosynthesis was found to be significantly less. When the same stress was applied, the total bending capacity of the ZESPOL system was found to be between 9% and 1348% higher, depending on the position of the plate and the direction of the force applied. In addition, the gap of the osteotomy site was between 6% and 923% greater with the ZESPOL system. Deformation of the bone adjacent to the osteotomy site was more closely approximate to intact bone with ACP than with ZESPOL plate. Our evaluations show that the ZESPOL system has less bending stability than ACP, without having the advantage of a more physiological bone-bending curve. However, the stability of the new system can be regarded as being overall sufficient.     

Development of subcutaneous wound oxygen measurement in humans: Contributions of Thomas K. Hunt, MD

When, in the early 1960s, Thomas K. Hunt, MD began investigating the role of oxygen in wound healing, he recognized that translation to humans would require the ability to measure oxygen tension in human wounds. This article will review his contributions to the development of subcutaneous tissue oxygen measurement and to the understanding of wound physiology and oxygen delivery, particularly through use of oxygen measurement. Hunt's major contributions to the field include the observations that all wounds show some degree of hypoxia, while many are severely hypoxic; the degree of hypoxia in wounds is sufficient to impair wound healing, and particularly bacterial killing by neutrophils, collagen deposition, angiogenesis, and epithelization; the sympathetic nervous system plays a central role in decreasing wound oxygen supply; and wound oxygen delivery and wound healing capacity can be increased by controlling the sympathetic nervous system. All these observations required tissue oxygen measurement, and, in particular, translation of basic scientific observations to clinical research required a method of measuring wound oxygen tension in humans.     

Application of extracorporeal shock-waves in the treatment of pseudarthrosis of the lower extremity

Between January 1991 and January 1996, pseudarthroses of the legs were treated prospectively in 48 patients by application of high-energy extracorporeal shock waves with an experimental device. The mean duration of pseudarthrosis was 12 months. On average, 2.4 surgical interventions had previously been performed. A total of 3000 impulses with an energy density of 0.6 mJ/mm² was applied to the pseudarthrosis. Bony union was achieved in 60.4% of our patients after an average of 3.4 months. Failures were found especially in the atrophic types of pseudarthrosis as well as in congenital bone disorders like fibrous dysplasia or osteogenesis imperfecta. No serious complications were observed. Even after numerous surgical interventions high-energy extracorporeal shock-wave therapy showed a fair success rate. A higher success rate of this non-invasive method for the treatment of bony non-unions may be expected by applying strict selection criteria.     

Sensitivity of laser-evoked potentials versus somatosensory evoked potentials in patients with multiple sclerosis.

OBJECTIVE: Somatosensory evoked potentials (SEPs) play a less important role in the diagnosis of multiple sclerosis (MS) than visually evoked potentials. Since standard SEPs only reflect the dorsal column function, we now investigated spinothalamic tract function in patients with MS using laser-evoked potentials (LEPs). METHODS: LEPs to thulium laser stimuli (3ms, 540 mJ, 5mm diameter) were recorded from 3 midline positions (Fz, Cz, Pz) in 20 patients with MS, and 6 patients with possible but unconfirmed MS. Peak latencies and peak-to-peak amplitude of the vertex potential negativity (N2) and positivity (P2) were evaluated and compared with normative values from 22 healthy control subjects. Median and tibial nerve SEPs were recorded with standard methods. Depending on the results of sensory testing, two skin areas (both hands, both feet, or one hand and foot of the same body side) were assessed in each patient. RESULTS: In group comparisons, LEPs in patients with MS were significantly delayed and reduced in amplitude compared with healthy subjects (P<0.001) or patients with suspected but unconfirmed MS (P<0.05). In intraindividual comparisons within the patients with MS, LEP amplitude was significantly lower (P<0.01) and latencies were significantly longer (N2: P<0.01; P2: P<0.05) for a clinically hypoalgesic skin area than an unaffected control area. On a single case basis, LEPs were abnormal in 12 (60%) and SEPs in 8 (40%) of the patients with MS; combined analysis of LEPs and SEPs raised sensitivity to 75% (15 patients). LEPs were also abnormal for 7 skin areas with clinically normal nociception and thermal sensitivity, indicating subclinical lesions. Standard SEPs detected subclinical lesions in 5 areas with normal tactile sensitivity. CONCLUSIONS: In patients with multiple sclerosis, spinothalamic tract function and LEPs were impaired more often than dorsal column function and SEPs. LEPs also detected subclinical lesions. Combined assessment of LEPs and SEPs can help to document dissemination of demyelinating CNS lesions and thus contribute to the diagnosis of multiple sclerosis.