Biomedical subjects

John Wilkinson

Publications and source records attributed to John Wilkinson.

28 records · Page 2Linked to original sources

PubMed2003

Comparison of the influence of volume-oriented training and high-intensity interval training on serum homocysteine and its cofactors in young, healthy swimmers.

BACKGROUND: Since homocysteine (Hcy) is a risk factor for cardiovascular and other diseases, it is important to know how exercise can modify it. Previous studies have suggested that endurance training influences Hcy. However, little is known about the effect of training intensity on Hcy. MATERIALS AND METHODS: We investigated Hcy, vitamin B12, vitamin B6, folate and methylmalonic acid (MMA) before and after 3 weeks of volume-oriented training (VOL) (30 km/week) and high-intensity interval training (HIT) (20 km/week) in 20 young swimmers (16 +/- 2 years). Afterward, the athletes completed 5 days of recovery training. RESULTS: The training induced a Hcy increase in HIT and VOL (6.47 +/- 0.95 micromol/l vs. 7.44 +/- 1.17 micromol/l and 7.33 +/- 1.92 micromol/l vs. 8.28 +/- 1.42 micromol/l, respectively) that persisted during the recovery period (8.02 +/- 1.69 micromol/l and 8.00 +/- 1.81 micromol/l, respectively). Vitamin B12 was unchanged after the training (539 +/- 166 ng/l vs. 556 +/- 192 ng/l and 480 +/- 144 ng/l vs. 491 +/- 124 ng/l, respectively) but decreased during the recovery period (459 +/- 134 ng/l and 451 +/- 116 ng/l, respectively). Folate showed an increase during the training (9.07 +/- 2.01 microg/l vs. 11.71 +/- 4.08 microg/l and 10.34 +/- 2.32 microg/l vs. 11.13 +/- 4.64 microg/l, respectively), which was reversible by the end of the recovery training (8.57 +/- 1.98 microg/l and 9.60 +/- 2.38 microg/l, respectively). Vitamin B6 and MMA did not change. For none of the measured parameters were there significant differences between HIT and VOL. CONCLUSION: Three weeks of strenuous swimming caused a prolonged Hcy increase, which was accompanied by changes in vitamin B12 and folate. The magnitude of these effects was not influenced by the training intensity.

Adolescent↗

PubMed2002

Prospective study of the effects of antiretroviral therapy on Kaposi sarcoma--associated herpesvirus infection in patients with and without Kaposi sarcoma.

OBJECTIVE: To investigate the effect of highly active antiretroviral therapy (HAART) on circulating Kaposi sarcoma (KS)-associated herpesvirus (KSHV) load in HIV-infected individuals with and without KS. DESIGN: Twenty-nine HIV-infected subjects (21 with KS and 8 without KS) were recruited for the study; they were prospectively studied before and at regular intervals during HAART. METHODS: Patients with KS were clinically assessed using Adult Clinical Trials Group (ACTG) criteria, and sequential blood samples were obtained from all patients for determination of plasma HIV-1 load, CD4 cell count, titer of antibody to KSHV, and KSHV load. RESULTS: Ten of 21 patients with KS had a favorable KS response (complete response, 6; partial response, 4) with HAART alone. Of the 20 subjects with detectable KSHV viremia prior to HAART, over one half (12 [60%]) had an undetectable KSHV load with antiretroviral therapy. There was no significant difference between subjects receiving protease inhibitor- or nonnucleoside reverse transcriptase inhibitor-based treatment combinations. Achieving undetectable KSHV viremia is associated with a better clinical outcome in patients with KS. CONCLUSIONS: To our knowledge, we demonstrate for the first time that both protease inhibitor-based and nonnucleoside reverse transcriptase inhibitor-based antiretroviral treatment combinations may lead to an undetectable KSHV load and confirm that an undetectable KSHV load is associated with KS regression. There was no clear association between CD4 cell count response and KS response to HAART, but there was a significant relationship between HIV load response to HAART and clinical improvement of KS.

Adult↗

PubMed2002

Activation of caspase pathways during iron chelator-mediated apoptosis.

Iron chelators have traditionally been used in the treatment of iron overload. Recently, chelators have also been explored for their ability to limit oxidant damage in cardiovascular, neurologic, and inflammatory disease as well as to serve as anti-cancer agents. To determine the mechanism of cell death induced by iron chelators, we assessed the time course and pathways of caspase activation during apoptosis induced by iron chelators. We report that the chelator tachpyridine sequentially activates caspases 9, 3, and 8. These caspases were also activated by the structurally unrelated chelators dipyridyl and desferrioxamine. The critical role of caspase activation in cell death was supported by microinjection experiments demonstrating that p35, a broad spectrum caspase inhibitor, protected HeLa cells from chelator-induced cell death. Apoptosis mediated by tachpyridine was not prevented by blocking the CD95 death receptor pathway with a Fas-associated death domain protein (FADD) dominant-negative mutant. In contrast, chelator-mediated cell death was blocked in cells microinjected with Bcl-XL and completely inhibited in cells microinjected with a dominant-negative caspase 9 expression vector. Caspase activation was not observed in cells treated with N-methyl tachpyridine, an N-alkylated derivative of tachpyridine which lacks an ability to react with iron. These results suggest that activation of a mitochondrial caspase pathway is an important mechanism by which iron chelators induce cell death.

Apoptosis↗

PubMed2002

Fragrance contact dermatitis - a worldwide multicenter investigation (Part III).

The purpose of this study was to determine the frequency of responses to selected fragrance materials in patients who were fragrance sensitive. 218 fragrance sensitive subjects were evaluated in eight centres worldwide with a fragrance mixture (FM) and 17 less well-studied fragrance materials. Reaction to the fragrance mixture (FM) occurred in 76% of the subjects. The (FM) detected all reactions to nerol and hydroxycitronellol and 93% of the reactions to clove bud oil. Ten fragrance materials were not detected by the FM and deserve further study: benzenepropanol, beta, beta, 3-trimethyl, hexyl-salicylate, dl-citronellol, synthetic ylang ylang oil, benzyl mixture, cyclohexyl-acetate, eugenyl methyl ether, isoeugenyl methyl ether, 3-phenyl-1-propanol, and 3, 7-dimethyl-7-methoxyoctan-2-ol.

Adult↗

PubMed2002

Identification of Kaposi's sarcoma-associated herpesvirus (KSHV)-specific cytotoxic T-lymphocyte epitopes and evaluation of reconstitution of KSHV-specific responses in human immunodeficiency virus type 1-Infected patients receiving highly active antiretroviral therapy.

Following the introduction of highly active antiretroviral therapy (HAART), the incidence of Kaposi's sarcoma (KS) has significantly declined in human immunodeficiency virus type 1 (HIV-1)-positive (HIV-1(+)) individuals and clinical remission is often observed. We hypothesize that these effects are partly due to anti-KS-associated herpesvirus (KSHV) immune restoration. Here, 15-mer overlapping peptides from proteins K12 and K8.1 were used to identify novel KSHV-specific cytotoxic T-lymphocyte epitopes. Three immunogenic peptides, two lytic and one latent, were subsequently used to monitor the anti-KSHV CD8(+) T-cell responses in a cohort of 19 HIV-1(+) KSHV(+/-) KS(+/-) individuals during 52 weeks of HAART. KSHV and HIV-1 loads, KSHV antibody titers, and both CD4(+) and CD8(+) T-lymphocyte counts were enumerated. Prior to HAART, the total number of spot-forming cells (SFC) for all three peptides correlated with both CD4(+) and CD8(+) T-lymphocyte counts (P < or = 0.05) in the KSHV-positive KS-positive cohort (n = 11). Following 52 weeks of HAART, significant decreases in HIV-1 and KSHV loads were associated with significant increases in CD4(+) T-lymphocyte counts and number of SFC for the three KSHV-specific peptides. Although these increases were modest in comparison to the number of SFC observed with the HIV-1 gag peptide SLYNTVATL, they represented a fourfold increase from the baseline, continuing an upward trend to week 52.

AIDS-Related Opportunistic Infections↗

PubMed2002

Health needs assessment and needs-led health service change: a survey of projects involving public health doctors.

OBJECTIVES: To describe the criteria that define an effective health needs assessment and to explore which factors are important for the delivery of effective health needs assessment in the English National Health Service (NHS). METHODS: A postal questionnaire to all public health doctors in an English health region to describe health needs assessment activity, including initiating factors, methods and outcomes. This was followed by semi-structured interviews with public health professionals and others involved in 10 purposively selected needs assessments. RESULTS: A response rate of 62% identified a total of 102 health needs assessments undertaken between 1993 and 1998. A number of themes emerged as being important in the impact of health needs assessments on policy and planning. These included careful design, methodological rigour, decisive leadership, good communication, involvement and ownership of the work from relevant stakeholders, support from senior decision-makers, appreciation of the political dynamics and engagement with local priorities, availability of resources and, finally, an element of chance. These themes can be categorised broadly into contextual factors and quality or robustness of the work. Our findings suggest that, although methodological and analytical quality are necessary characteristics of effective health needs assessment, they are not sufficient without a favourable political environment. CONCLUSION: There appear to be conditions under which needs assessment is more likely to be effective in terms of its influence on policy and planning. However, it is clear that needs assessment does not occupy a central position in health service decision-making, remaining vulnerable to a range of factors over which those responsible for its conduct have little or no control.

Attitude of Health Personnel↗

PubMed2002

The chemopreventive agent oltipraz possesses potent antiangiogenic activity in vitro, ex vivo, and in vivo and inhibits tumor xenograft growth.

Angiogenesis plays a pivotal role in tumor growth and represents a key target for chemopreventive intervention. On the basis of the structural features and lack of target organ specificity of the synthetic dithiolethione oltipraz, inhibition of angiogenesis was assessed as a potential mechanism for its broad-based chemopreventive activity. The effects of oltipraz on the development and maturation of a vascular network was determined in vitro using two-dimensional capillary tube formation assays with human umbilical vein endothelial cells plated on Matrigel and ex vivo using primary rat aortic ring explant cultures in three-dimensional collagen gels, respectively. The antiangiogenic and antitumor efficacy of oltipraz administration in vivo in nude mice was evaluated by determining its effects on neovascularization in s.c. Matrigel implants seeded with vascular endothelial growth factor and basic fibroblast growth factor-stimulated porcine aortic endothelial cells and on tumor growth and angiogenesis in SVR murine angiosarcoma xenografts implanted s.c. A dose-dependent reduction (0.4-100 microM) in microvessel formation was observed in both human and rodent bioassays after oltipraz exposure, with inhibition approaching 100% in the rat aortic ring assay at the highest concentration (P < 0.01). Similarly, oltipraz (40 microM) inhibited complete capillary tube formation by human umbilical vein endothelial cells by 62% (P < 0.05) relative to control cultures. p.o. administration of oltipraz (250 mg/kg/day for 6 days) to nude mice implanted with porcine aortic endothelial cell-Matrigel plugs resulted in a 42% reduction in neovascularization (P < 0.05) relative to vehicle-treated control mice. Administration of the same dose of oltipraz to athymic mice bearing established s.c. SVR angiosarcoma xenografts for 10 days resulted in a significant inhibition of tumor growth as early as day 4 of dosing (P < 0.005), with a maximum inhibition of tumor growth (81%, P < 0.001) relative vehicle-treated mice by day 10. The observed efficacy of oltipraz in this model is comparable with that of SU 5416 and TNP-470, known antiangiogenic agents currently under clinical development. Plasma levels of oltipraz at the termination of in vivo efficacy studies were 66.4 +/- 7 microM as determined by reversed phase high-performance liquid chromatography, a concentration range associated with significant antiangiogenic activity of oltipraz in vitro and ex vivo. These data suggest that the chemopreventive agent oltipraz may be effective in the treatment of advanced stage cancers and metastases, in part, because of its antiangiogenic activity in vivo.

Angiogenesis Inhibitors↗

PubMedDate not supplied

The impact of detention on the health of asylum seekers.

Asylum seekers arriving in the United States are often imprisoned for months or years while their asylum claims are processed. Recently, Physicians for Human Rights and the Bellevue/New York University Program for Survivors of Torture released the findings of the first systematic study examining the health of detained asylum seekers. The study found that the mental health of asylum seekers interviewed was extremely poor, including high levels of symptoms for anxiety, depression, and posttraumatic stress disorder, which worsened the longer individuals were in detention. The study also raises concerns about the manner in which asylum seekers are treated upon arrival in the United States and then while in detention. These findings support assertions that detention has a harmful effect on the health and well-being of asylum seekers. Policies regarding the long-term detention of asylum seekers should be reconsidered.

Anxiety↗

PubMedDate not supplied

Contact sensitivity to hair dyes can be detected by the consumer open test.

To avoid allergic reactions to hair dyes, an open test ("skin sensitivity test" or "dab test") is recommended 48 hours before the hair colouring procedure. We have investigated in a multicenter study, under standardized conditions and medical supervision, the validity of this test as a practical method to detect allergy to paraphenylenediamine (PPD)-containing hair dyes in 30 PPD patch test-positive and 30 PPD patch test-negative subjects. A defined volume of a marketed hair colouring product containing 1.8% PPD was applied in an open patch test to the retroauricular area. The grading method comprised the dermatologist's clinical evaluation and objective numerical scores. Allergic reactions were elicited in all PPD-positive subjects with a maximal intensity on Day 2; no allergic reactions were elicited in PPD-negative subjects. Increased severity of reactions by the dermatologist's clinical evaluation was correlated strongly with increasing numerical scores. The "skin sensitivity test" can be considered as an effective method to detect type IV hair dye allergy and as such, as an important factor in its secondary prevention.

Adolescent↗

PubMedDate not supplied

Sensitivity and specificity of the consumer open skin allergy test as a method of prediction of contact dermatitis to hair dyes.

To prevent contact dermatitis to oxidative hair colouring products, a consumer test (skin allergy test, SAT) consisting of the open application of the colourant base prior to mixing with the developer is recommended 48 hours before hair colouring. We investigated the sensitivity and specificity of the SAT to detect and prevent contact allergy to oxidative hair colouring products that contained a range of concentrations of para-phenylenediamine (PPD) and corresponded to different shades (light, medium and dark). Test colouring products containing increasing concentrations of PPD (0.1, 0.5, 1.0 or 1.5%) were applied to 34 PPD-positive hair dye-allergic individuals and to 49 non-allergic control subjects. Allergic reactions were elicited in all PPD-positive subjects whereas none occurred in control PPD-negative subjects. For each subject the eliciting concentration of PPD in the SAT was compared with the PPD concentration range of the group of commercial shades reported as causing reactions by the consumer. In all PPD-positive subjects the eliciting concentrations of PPD in the SAT was within or lower than the range of PPD concentrations in the reported eliciting colourant base of commercial products. In conclusion, our results confirm the excellent predictive value of the SAT over the entire range of PPD concentrations used in oxidative hair colouring products and suggest that the test is a suitable tool for the secondary prevention of contact allergic reactions to hair colouring products.

Adult↗