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21.
Data on the burden of visceral leishmaniasis (VL) in Indian sub-continent are vital for elimination programme planners for estimating resource requirements, effective implementation and monitoring of elimination programme. In Indian sub-continent, about 200 million population is at risk of VL. Nearly 25,000-40,000 cases and 200-300 deaths are reported every year, but these are grossly underestimates. Recent well-designed multicentric studies identified VL burden of 21 cases/10,000 among sampled population in Indian sub-continent (Bangladesh, India and Nepal). This estimates 4,20,000 cases per 200 million risk population clearly indicating that the disease is highly under-reported. Chemical and environmental vector control studies show that the indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) are effective and significantly reduce sandfly densities. The findings documented from different sources revealed that some gaps and weakness in existing policies for introducing VL vector control interventions. Our studies emphasize the need of integrated vector management with both IRS and LLIN vector control interventions. Active case detection with rK39 strip test as diagnostic tool is the key element for detection of VL cases. The use of oral drug miltefosine for the treatment after assessing feasibility at community level is important. Kala-azar elimination in Indian sub-continent is possible if elimination programmes ensure access to health care and prevention of kala-azar for people at risk with particular attention to the poorest and marginalized groups. The evidence-based policy should be designed that motivates to implement the programmes, which will be cost-effective. Maintaining the acceptable level of incidence requires public awareness, vector control, appropriate diagnosis and treatment. The five pillars of VL elimination strategies identified are: early diagnosis and complete treatment; integrated vector management and vector surveillance; effective disease surveillance through passive and active case detection; social mobilization and building partnerships; and clinical and operational research which need to be re-enforced to effective implementation.  相似文献   
22.
23.

Objective

Patients with chronic obstructive pulmonary disease (COPD) present systemic inflammation. Strenuous resistive breathing induces systemic inflammation in healthy subjects. We hypothesized that the increased respiratory load that characterizes COPD can contribute to systemic inflammation in these patients.

Patients and methods

To test this hypothesis, we compared leukocyte numbers and levels of circulating cytokines (tumor necrosis factor alpha [TNFα], interleukin-1β [IL-1β], IL-6, IL-8, and IL-10), before and 1 hour after maximal incremental inspiratory loading in 13 patients with stable COPD (forced expiratory volume in one second [FEV1] 29 ± 2.5% ref) and in 8 healthy sedentary subjects (FEV1 98 ± 5% ref).

Results

We found that: (1) at baseline, patients with COPD showed higher leukocyte counts and IL-8 levels than controls (p < 0.01); and, (2) one hour after maximal inspiratory loading these values were unchanged, except for IL-10, which increased in controls (p < 0.05) but not in patients with COPD.

Conclusions

This study confirms the presence of systemic inflammation in COPD, shows that maximal inspiratory loading does not increase the levels of pro-inflammatory cytokines (IL-1β, IL-8) in COPD patients or controls, but suggests that the former may be unable to mount an appropriate systemic anti-inflammatory response to exercise.  相似文献   
24.
Although the family Trypanosomatidae includes parasites of plants, insects and vertebrates, only two genera in the family, Leishmania and Trypanosoma, are usually found in humans. Since 1995, however, other monoxenous trypanosomatids have been isolated from several HIV-positive individuals, in whom the parasites cause either visceral or cutaneous lesions. These odd cases are reviewed here. It appears that immunocompromised patients may be vulnerable to infection with trypanosomatids (and other parasites) that either fail to survive or never cause detectable morbidity in the immunocompetent.  相似文献   
25.
Clinical Autonomic Research - The effects of exercise-based cardiac rehabilitation (CR) on parasympathetic modulation are controversial. This systematic review and meta-analysis aims to (a)...  相似文献   
26.
27.

Introduction and objectives

To assess the validity of the original low-risk SCORE function without and with high-density lipoprotein cholesterol and SCORE calibrated to the Spanish population.

Methods

Pooled analysis with individual data from 12 Spanish population-based cohort studies. We included 30 919 individuals aged 40 to 64 years with no history of cardiovascular disease at baseline, who were followed up for 10 years for the causes of death included in the SCORE project. The validity of the risk functions was analyzed with the area under the ROC curve (discrimination) and the Hosmer-Lemeshow test (calibration), respectively.

Results

Follow-up comprised 286 105 persons/y. Ten-year cardiovascular mortality was 0.6%. The ratio between estimated/observed cases ranged from 9.1, 6.5, and 9.1 in men and 3.3, 1.3, and 1.9 in women with original low-risk SCORE risk function without and with high-density lipoprotein cholesterol and calibrated SCORE, respectively; differences were statistically significant with the Hosmer-Lemeshow test between predicted and observed mortality with SCORE (P < .001 in both sexes and with all functions). The area under the ROC curve with the original SCORE was 0.68 in men and 0.69 in women.

Conclusions

All versions of the SCORE functions available in Spain significantly overestimate the cardiovascular mortality observed in the Spanish population. Despite the acceptable discrimination capacity, prediction of the number of fatal cardiovascular events (calibration) was significantly inaccurate.Full English text available from:www.revespcardiol.org/en  相似文献   
28.

Introduction

Thiopurine therapy can be optimised by determining the concentration of the drug's metabolites.

Patients and methods

Retrospective analysis on a prospective database of 31 patients with inflammatory bowel disease who failed therapy with thiopurines. Thiopurine metabolites (6-thioguanine, 6-TGN and 6-methylmercaptopurine, 6-MMP) were measured by high-performance liquid chromatography (Laboratorios Cerba, Barcelona) and treatment was duly adjusted in accordance with the results. Clinical response was reassessed after six months.

Result

Despite the appropriate theoretical dose of thiopurines being administered, the dose was insufficient in 45.6% of patients (nonadherence to treatment suspected in 6.45%) and 16.2% received an excessive dose or the drug was metabolised by other metabolic pathways. After treatment was optimised based on metabolite levels, only 25.8% (8/31) were prescribed a biological agent, while 74.2% of cases (23/31) were managed through dose optimisation alone.

Discussion

Monitoring thiopurine metabolite levels may help clinicians to assess non-responsive patients before adding or switching to another drug (generally a biological agent), thereby avoiding any additional costs or potential toxicity. This strategy may also help to identify patients receiving an insufficient dose and those with an alternative metabolic pathway, who could be candidates for low-dose AZA with allopurinol, as well as patients who are suspected of being non-adherent. In three out of four patients, switching to a biological agent can be avoided.  相似文献   
29.
The regulation of gap junctional communication by histamine was studied in primary cultures of human tonsil high endothelial cells (HUTECs). We evaluated intercellular communication, levels, state of phosphorylation, and cellular distribution of gap junction protein subunits, mainly connexin (Cx)43. Histamine induced a time-dependent reduction in dye coupling (Lucifer yellow) associated with reduction in connexin43 localized at cell-cell appositions (immunofluorescence), without changes in levels and phosphorylation state of connexin43 (immunoblots). These effects were prevented with chlorpheniramine, an H1 receptor blocker; indomethacin, a cyclooxygenase blocker; or GF109203X, a protein kinase C inhibitor. Treatment with phorbol myristate acetate, a protein kinase C activator, and 4bromo (4Br)-A23187, a calcium ionophore, mimicked the histamine-induced effects on dye coupling. 8Bromo-cAMP doubled the dye coupling extent and prevented the histamine-induced reduction in incidence of dye coupling. After 24-h histamine treatment, known to desensitize H1 receptors, reapplication of histamine increased cell coupling in a way prevented by ranitidine, an H2 receptor blocker. Thus, activation of H1 and H2 receptors, which increase intracellular levels of free Ca2+ and cAMP, respectively, may affect gap junctional communication in opposite ways. Stabilization of actin filaments with phalloidine diminished but did not totally prevent histamine-induced cell shape changes and reduction in dye coupling. Hence, the histamine-induced reduction in gap junctional communication between HUTEC is mediated by cytoskeleton-dependent and -independent mechanisms and might contribute to modulate endothelial function in lymphoid tissue.  相似文献   
30.
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