The incidence of venous thromboembolism in commercial airline pilots: a cohort study of 2630 pilots.

BACKGROUND: Airline pilots may be at increased risk of venous thromboembolism (VTE) because air travel has recently been established as a risk factor for VTE. OBJECTIVES: The aim of this study was to assess the risk of VTE in a cohort of Dutch airline pilots. PATIENTS/METHODS: Airline pilots who had been active members of the Dutch aviation society (VNV) were questioned for the occurrence of VTE, presence of risk factors for VTE and number of flight hours per year and rank. Incidence rates among pilots were compared with those of the general Dutch population and with a population of frequently flying employees of multinational organizations. RESULTS AND CONCLUSIONS: A total of 2630 male pilots were followed-up for a total of 20420 person-years (py). Six venous thromboses were reported, yielding an incidence rate of 0.3 per 1000 py. The standardized morbidity ratio, comparing these pilots with the general Dutch population adjusted for age, was 0.8. Compared with the international employee cohort, the standardized morbidity ratio was 0.7 when all employees were included and 0.6 when only the frequently travelling employees were included. The incidence rate did not increase with number of flight hours per year and did not clearly vary by rank. We conclude that the risk of VTE is not increased amongst airline pilots.

No effect of isolated long-term supine immobilization or profound prolonged hypoxia on blood coagulation.

BACKGROUND: Long-distance air travel is associated with an increased risk of venous thrombosis. The most obvious factor that can explain air travel-related thrombosis is prolonged seated immobilization. In addition, hypobaric hypoxia has been shown to affect coagulation, and the lowered atmospheric pressures present in the cabin during the flight may therefore play an etiologic role. Because immobilization and hypoxic conditions are usually present simultaneously in airplanes or hypobaric chambers, their separate effects on the coagulation system or on thrombosis risk have not been studied extensively. OBJECTIVES: To investigate the separate effects of long-term immobilization and profound prolonged hypoxia on blood coagulation. PATIENTS AND METHODS: We performed two studies in collaboration with European Space Agency/European Space Research and Technology Centre. In the first study, 24 healthy, non-smoking, adult women underwent 60 days of -6° head-down bed rest. In the second study, we took blood samples from 25 healthy men who participated during their stay in the Concordia station in Antarctica, where, due to the atmospheric conditions, continuous severe hypobaric hypoxia is present. In both studies, we measured markers of blood coagulation at baseline and at several time points during the exposures. RESULTS AND CONCLUSIONS: We observed no increase in coagulation markers during immobilization or in the hypobaric environment, compared with baseline measurements. Our results indicate that neither immobilization nor hypoxia per se affects blood coagulation. These results implicate that a combination of risk factors is necessary to induce the coagulation system during air travel.

Weight reduction, but not a moderate intake of fish oil, lowers concentrations of inflammatory markers and PAI-1 antigen in obese men during the fasting and postprandial state.

BACKGROUND: In obese subjects, chronic low-grade inflammation contributes to an increased risk of metabolic abnormalities, which are reversed by weight loss. Sustained weight loss, however, is difficult to achieve and more insight into dietary approaches on anti-inflammatory responses in obese subjects is needed. In this respect, fish oil deserves attention. MATERIAL AND METHODS: Eleven obese men (BMI: 30-35 kg m(-2)) received daily fish oil (1.35 g n-3 fatty acids) or placebo capsules in random order for 6 weeks. Eight subjects continued with a weight reduction study that lasted 8 weeks. Mean weight loss was 9.4 kg. At the end of each experimental period a postprandial study was performed. RESULTS: Relative to fasting concentrations, interleukin-6 (IL-6) levels increased by 75% 2 h and by 118% 4 h after the meal (P < 0.001), when subjects consumed the control capsules. In contrast, C-reactive protein (C-RP) concentrations decreased slightly by 0.7% and 6.6% (P = 0.046), and those of plasminogen activator inhibitor-1 (PAI-1) antigen by, respectively, 26% and 53% (P < 0.001). Tumour necrosis factor-alpha (TNF-alpha; P = 0.330) and soluble TNF-receptor concentrations (sTNF-R55 and sTNF-R75; P = 0.451 and P = 0.108, respectively) did not change. Changes relative to fasting concentrations were not significantly affected by either fish oil or weight reduction. Absolute IL-6, C-RP, sTNF-R55, sTNF-R75, and PAI-1 antigen concentrations, however, were consistently lower after weight reduction, but not after fish oil consumption. CONCLUSION: For slightly obese subjects a moderate intake of fish oil does not have the same favourable effects on markers for a low-grade inflammatory state as weight reduction.

Gly972Arg variant in the insulin receptor substrate-1 gene and association with Type 2 diabetes: a meta-analysis of 27 studies.

AIMS/HYPOTHESIS: Several case-control studies have examined the association between the Gly972Arg variant in the IRS-1 gene and Type 2 diabetes, but most had limited power and results could therefore be conflicting. METHODS: We systematically reviewed the literature by means of a meta-analysis and investigated sources of heterogeneity in results of different studies. RESULTS: The summary risk ratio, based on 3408 cases and 5419 control cases from 27 studies, was 1.25 (95% CI 1.05-1.48). The results, however, differed according to the type of study, method of verifying non-diabetic status of the control subjects, and age of the case subjects. Population-based studies reported lower odds ratios than hospital-based studies (OR 0.98, 95% CI 0.74-1.30 vs OR 1.43, 95% CI 1.17-1.74). Also, the diagnostic test to exclude diabetes amongst control subjects interacted with the association between the IRS-1 Gly972Arg variant and Type 2 diabetes (p=0.03). Finally, the odds ratio reduced with increasing age ( p=0.03). CONCLUSION/INTERPRETATION: Overall, carriers of the 972Arg variant of the IRS-1 gene are at a 25% increased risk of having Type 2 diabetes compared with non-carriers. The odds ratios are generally higher in hospital-based studies, including relatively young, symptomatic, cases.

Climate- and human-induced woody vegetation changes in Botswana and their implications for human adaptation.

For purposes of suggesting adaptive and policy options regarding the sustained use of forestry resources in Botswana, an analysis of the whole countrywide satellite data (showing the mean present distribution of vegetation in terms of species abundance and over all density) and the projection of vegetation cover changes using a simulation approach under different climatic scenarios were undertaken. The analysis revealed that changes in vegetation cover types due to human and natural causes have taken place since the first vegetation map was produced in 1971. In the southwest, the changes appear to be more towards an increasing prevalence of thorn trees; in the eastern part of the country where widespread bush encroachment is taking place, the higher population density suggests more human induced (agrarian-degradation) effects, while in the sparsely settled central Kalahari region, changes from tree savanna to shrubs may be indicative of the possible influence of climate with the associated effects of fires and local adaptations. Projection of future vegetation changes to about 2050 indicates degeneration of the major vegetation types due to the expected drying. Based on the projected changes in vegetation, current adaptive and policy arrangements are not adequate and as such a shift from the traditional adaptive approaches to community-based types is suggested. Defining forestry management units and adopting different management plans for the main vegetation stands that are found in Botswana are the major policy options.

The efficacy of Xialine in patients with xerostomia resulting from radiotherapy for head and neck cancer: a pilot-study.

Changes in subjective sensations due to xerostomia before and after administration of Xialine, a xanthan gum-based saliva substitute, were evaluated in 30 patients with radiation-induced xerostomia using the QLQ-H&N35. Xerostomia in general decreased with both Xialine and placebo to almost the same degree. A trend was seen for Xialine to improve problems with speech and senses.

Lysis of syngeneic tumor B cells by autoreactive cytotoxic T lymphocytes specific for a CD19 antigen-derived synthetic peptide.

Cytotoxic T lymphocytes (CTL) play an important role in the destruction of immunogenic tumors. A novel category of target antigens for CTL concerns normal differentiation antigens as most clearly demonstrated in human melanoma. In the case of B-cell cancers, differentiation antigens normally expressed on B cells may be useful targets. In this report, we have focused on the murine B-cell differentiation antigens CD19 and CD20. We have identified 18 peptide sequences on the basis of major histocompatibility complex (MHC) class-I binding-motifs as candidates for the induction of autoreactive CTL. Six of the peptides were capable of binding efficiently to either Kb or Db and were subsequently used for in vivo induction of CTL. Vaccination with each of three peptides led to peptide-specific CTL. Two peptides were derived from the mCD20 antigen and one from the mCD19 antigen. CTL specific for the mCD19-derived peptide were also capable of killing a syngeneic B-cell tumor line. Recognition of the peptide as well as the tumor cells was shown to be Kb restricted. This is the first report to show that autoreactive CTL recognizing peptides derived from B-cell-specific differentiation antigens can be generated by vaccination with a synthetic peptide.

The response of burn scars to intralesional verapamil. Report of five cases.

Postburn dermal scars can be aesthetically disfiguring and severely disabling. Existing medical and surgical strategies to prevent or to treat scars are all too often disappointing. More effective strategies are needed. It has been postulated that cell membrane calcium channel blockers could potentially trigger extracellular matrix degradation in dermal scars, resulting in scar volume reduction. To test this hypothesis, we studied the effects of intralesional verapamil hydrochloride therapy, 0.1 to 0.5 mmol/L, on scar volume and color in patients with burns. Our study chronicles five reports on arbitrarily selected clinical cases of hypertrophic burn scarring and the effect of therapy with intralesional verapamil. The cellular functions and processes explaining this effect are discussed. There were no significant side effects or complications from the verapamil therapy. It is now clear that regulation of fibroblast calcium metabolism is a safe and often effective strategy to treat hypertrophic scars. To our knowledge, this is the first clinical report of control of burn scar with calcium channel blockers.

Conformational analysis of the single-helical DNA fragment d(T-A-A-T) in aqueous solution. The combined use of NMR proton chemical shifts and coupling constants obtained at 300 MHz and 500 MHz.

Proton NMR studies at 300 MHz and 500 MHz were carried out on the tetranucleoside trisphosphate d(T-A-A-T). The thermodynamics of the three stacking interactions, derived from chemical shift versus temperature profiles, were used to extrapolate the observed coupling constants, measured at a range of temperatures, to values appropriate to the fully stacked forms of the molecule. The data were interpreted in terms of N and S pseudorotational ranges [ Altona , C. and Sundaralingham , M. (1972) J. Am. Chem. Soc. 94, 8205-8212]. It is shown that the stacked state of the molecule cannot be described by one conformer, but consists of one major structure (60%) in which all sugar rings have S-type geometry and another structure (30%) in which residue dT(4) has an N-type sugar. The remainder of the stacked states consists of one or more conformers with two or three sugar residues in the N-type pseudorotational range. Detailed geometrical models are proposed for the major stacked conformers encountered in aqueous solution.

Skin testing. A valuable predictor in thermal injury?

Delayed hypersensitivity skin testing, a prognosticator of sepsis in severely injured patients, has been reported to have varied usefulness following thermal trauma. Skin tests were immediately and sequentially performed with six recall skin-test antigens on 69 patients with burns on greater than 25% of their total body surface area (TBSA). Skin tests were also immediately and sequentially performed with the same recall skin-test antigens on 42 patients with less than 25% of TBSA burned, as controls. In addition, calorie intake was recorded for all patients. Of the 69 patients with greater than 25% of TBSA burned, nine were normal, 13 were relatively anergic, and 47 were anergic. Of the patients in the less than 25% group, 13 were normal, 16 were relatively anergic, and 13 were anergic. In evaluating these data, we concluded that totally anergic patients are no more likely to die of sepsis than are normally responsive patients, nor are they more likely to have sepsis than normal and relatively anergic patients.