We have investigated the earliest events in commitment of human epidermal keratinocytes to terminal differentiation. Phosphorylated Akt and caspase activation were detected in cells exiting the basal layer of the epid...We have investigated the earliest events in commitment of human epidermal keratinocytes to terminal differentiation. Phosphorylated Akt and caspase activation were detected in cells exiting the basal layer of the epidermis. Activation of Akt by retroviral transduction of primary cultures of human keratinocytes resulted in an increase in abortive clones founded by transit amplifying cells, while inhibition of the upstream kinase, PI3-kinase, inhibited suspension-induced terminal differentiation. Caspase inhibition also blocked differentiation, the primary mediator being caspase 8. Caspase activation was initiated by 2 h in suspension, preceding the onset of expression of the termi- nal differentiation marker involucrin by several hours. Incubation of suspended cells with fibronectin or inhibition of PI3-kinase prevented caspase induction. At 2 h in suspension, keratinocytes that had become committed to terminal differentiation had increased side scatter, were 7-aminoactinomycin D （7-AAD） positive and annexin V negative; they exhibited loss of mitochondrial membrane potential and increased cardiolipin oxidation, but with no increase in reac- tive oxygen species. These properties indicate that the onset of terminal differentiation, while regulated by PI3-kinase and caspases, is not a classical apoptotic process.展开更多
Background： Direct ZN （Ziehl-Neelsen） sputum smear microscopy for diagnosis of TB （tuberculosis） has low sensitivity, especially in TB/HIV co-infected patients. Sputum concentration by bleach （NaOCI） with sedim...Background： Direct ZN （Ziehl-Neelsen） sputum smear microscopy for diagnosis of TB （tuberculosis） has low sensitivity, especially in TB/HIV co-infected patients. Sputum concentration by bleach （NaOCI） with sedimentation has been used to increase the sensitivity of sputum smear microscopy in many settings but with varying results. Objective： To determine whether bleach plus centrifugation significantly improves the detection of AFB （acid-fast bacilli） in ZN smear-negative sputum specimens. Methods： Three hundred and seventy sputum specimens were collected from new TB suspects attending a Nairobi referral district hospital and processed for direct microscopy using ZN technique and culture on Lowenstein Jensen Media. All smear-negative specimens were treated with 3.5% bleach and left to stand for 30 min before centrifugation. The bleach treated smears were processed and examined using ZN technique. Results： Of the 370 specimens, 200 （54%） were positive culture. The number of sputum samples that were smear-positive by direct ZN was 138 （37.2%）, with a sensitivity of 66%. After treatment of direct ZN smear-negative specimens with 3.5% bleach and centrifugation, the total number of AFB smear-positive samples increased to 171 with an increase in sensitivity of 66% to 81.1% （15.1%）. Conclusion： In this study, bleach with centrifugation significantly increased the yield of sputum smear microscopy. Further evaluation of these techniques in routine programmes is required especially in settings where the burden of TB/HIV is high.展开更多
Introduction： Recently rapid development of drug resistant TB, particularly MDR TB （Multi Drug Resistant TB） and XDRTB （Extensively Drug-Resistant TB） possess a major threat to control of tuberculosis globally. I...Introduction： Recently rapid development of drug resistant TB, particularly MDR TB （Multi Drug Resistant TB） and XDRTB （Extensively Drug-Resistant TB） possess a major threat to control of tuberculosis globally. Information on the extent of MDR-TB from Kenya is largely limited due to several factors. Monitoring of development of resistance is a vital tool in providing critical information for effective planning for TB control and in management of patients infected with TB. Methods： Cross-sectional with cluster design. Results： A total of 2,171 participants recruited into the study from 50 selected clusters. Prevalence of rifampicin resistance for new cases was 1.3% [95% CI, 0.8-2.0] and INH resistance was 5.5% [95% CI, 4.5-6.7]. MDR TB was found in 0.67% of new cases and 2.1% amongst previously treated TB cases. Discussion： Resistance to isoniazid in Kenya has been on the decline due to introduction of rifampicin in combined therapy. There was increase of MDR TB among new cases by 24% and decline in previously treated cases due to lethal impact of HIV. Conclusions： Although drug resistance TB is a growing problem in Kenya, resistance to isoniazid and rifampicin MDR TB is less than previously estimated. The country should continue to monitor drug resistance and ensure effective use of anti TB medicines.展开更多
Background::Despite free diagnosis and treatment for tuberculosis(TB),the costs during treatment impose a significant financial burden on patients and their households.The study sought to identify the determinants for...Background::Despite free diagnosis and treatment for tuberculosis(TB),the costs during treatment impose a significant financial burden on patients and their households.The study sought to identify the determinants for cata-strophic costs among patients with drug-sensitive TB(DSTB)and their households in Kenya.Methods::The data was collected during the 2017 Kenya national patient cost survey from a nationally representative sample(n=1071).Treatment related costs and productivity losses were estimated.Total costs exceeding 20%of household income were defined as catastrophic and used as the outcome.Multivariable Poisson regression analysis was performed to measure the association between selected individual,household and disease characteristics and occurrence of catastrophic costs.A deterministic sensitivity analysis was carried using different thresholds and the significant predictors were explored.Results::The proportion of catastrophic costs among DSTB patients was 27%(n=294).Patients with catastrophic costs had higher median productivity losses,39 h[interquartile range(IQR):20-104],and total median costs of USD 567(IQR:299-1144).The incidence of catastrophic costs had a dose response with household expenditure.The poorest quintile was 6.2 times[95%confidence intervals(CI):4.0-9.7]more likely to incur catastrophic costs compared to the richest.The prevalence of catastrophic costs decreased with increasing household expenditure quintiles(proportion of catastrophic costs:59.7%,32.9%,23.6%,15.9%,and 9.5%)from the lowest quintile(Q1)to the highest quintile(Q5).Other determinants included hospitalization:prevalence ratio(PR)=2.8(95%CI:1.8-4.5)and delayed treatment:PR=1.5(95%CI:1.3-1.7).Protective factors included receiving care at a public health facility:PR=0.8(95%CI:0.6-1.0),and a higher body mass index(BMI):PR=0.97(95%CI:0.96-0.98).Pre TB expenditure,hospitalization and BMI were significant predictors in all sensitivity analysis scenarios.Conclusions::There are significant inequities in the occurrence of catastrophic costs.Social protection interventions in addition to existing medical and public health interventions are important to implement for patients most at risk of incurring catastrophic costs.展开更多
文摘We have investigated the earliest events in commitment of human epidermal keratinocytes to terminal differentiation. Phosphorylated Akt and caspase activation were detected in cells exiting the basal layer of the epidermis. Activation of Akt by retroviral transduction of primary cultures of human keratinocytes resulted in an increase in abortive clones founded by transit amplifying cells, while inhibition of the upstream kinase, PI3-kinase, inhibited suspension-induced terminal differentiation. Caspase inhibition also blocked differentiation, the primary mediator being caspase 8. Caspase activation was initiated by 2 h in suspension, preceding the onset of expression of the termi- nal differentiation marker involucrin by several hours. Incubation of suspended cells with fibronectin or inhibition of PI3-kinase prevented caspase induction. At 2 h in suspension, keratinocytes that had become committed to terminal differentiation had increased side scatter, were 7-aminoactinomycin D （7-AAD） positive and annexin V negative; they exhibited loss of mitochondrial membrane potential and increased cardiolipin oxidation, but with no increase in reac- tive oxygen species. These properties indicate that the onset of terminal differentiation, while regulated by PI3-kinase and caspases, is not a classical apoptotic process.
文摘Background： Direct ZN （Ziehl-Neelsen） sputum smear microscopy for diagnosis of TB （tuberculosis） has low sensitivity, especially in TB/HIV co-infected patients. Sputum concentration by bleach （NaOCI） with sedimentation has been used to increase the sensitivity of sputum smear microscopy in many settings but with varying results. Objective： To determine whether bleach plus centrifugation significantly improves the detection of AFB （acid-fast bacilli） in ZN smear-negative sputum specimens. Methods： Three hundred and seventy sputum specimens were collected from new TB suspects attending a Nairobi referral district hospital and processed for direct microscopy using ZN technique and culture on Lowenstein Jensen Media. All smear-negative specimens were treated with 3.5% bleach and left to stand for 30 min before centrifugation. The bleach treated smears were processed and examined using ZN technique. Results： Of the 370 specimens, 200 （54%） were positive culture. The number of sputum samples that were smear-positive by direct ZN was 138 （37.2%）, with a sensitivity of 66%. After treatment of direct ZN smear-negative specimens with 3.5% bleach and centrifugation, the total number of AFB smear-positive samples increased to 171 with an increase in sensitivity of 66% to 81.1% （15.1%）. Conclusion： In this study, bleach with centrifugation significantly increased the yield of sputum smear microscopy. Further evaluation of these techniques in routine programmes is required especially in settings where the burden of TB/HIV is high.
文摘Introduction： Recently rapid development of drug resistant TB, particularly MDR TB （Multi Drug Resistant TB） and XDRTB （Extensively Drug-Resistant TB） possess a major threat to control of tuberculosis globally. Information on the extent of MDR-TB from Kenya is largely limited due to several factors. Monitoring of development of resistance is a vital tool in providing critical information for effective planning for TB control and in management of patients infected with TB. Methods： Cross-sectional with cluster design. Results： A total of 2,171 participants recruited into the study from 50 selected clusters. Prevalence of rifampicin resistance for new cases was 1.3% [95% CI, 0.8-2.0] and INH resistance was 5.5% [95% CI, 4.5-6.7]. MDR TB was found in 0.67% of new cases and 2.1% amongst previously treated TB cases. Discussion： Resistance to isoniazid in Kenya has been on the decline due to introduction of rifampicin in combined therapy. There was increase of MDR TB among new cases by 24% and decline in previously treated cases due to lethal impact of HIV. Conclusions： Although drug resistance TB is a growing problem in Kenya, resistance to isoniazid and rifampicin MDR TB is less than previously estimated. The country should continue to monitor drug resistance and ensure effective use of anti TB medicines.
文摘Background::Despite free diagnosis and treatment for tuberculosis(TB),the costs during treatment impose a significant financial burden on patients and their households.The study sought to identify the determinants for cata-strophic costs among patients with drug-sensitive TB(DSTB)and their households in Kenya.Methods::The data was collected during the 2017 Kenya national patient cost survey from a nationally representative sample(n=1071).Treatment related costs and productivity losses were estimated.Total costs exceeding 20%of household income were defined as catastrophic and used as the outcome.Multivariable Poisson regression analysis was performed to measure the association between selected individual,household and disease characteristics and occurrence of catastrophic costs.A deterministic sensitivity analysis was carried using different thresholds and the significant predictors were explored.Results::The proportion of catastrophic costs among DSTB patients was 27%(n=294).Patients with catastrophic costs had higher median productivity losses,39 h[interquartile range(IQR):20-104],and total median costs of USD 567(IQR:299-1144).The incidence of catastrophic costs had a dose response with household expenditure.The poorest quintile was 6.2 times[95%confidence intervals(CI):4.0-9.7]more likely to incur catastrophic costs compared to the richest.The prevalence of catastrophic costs decreased with increasing household expenditure quintiles(proportion of catastrophic costs:59.7%,32.9%,23.6%,15.9%,and 9.5%)from the lowest quintile(Q1)to the highest quintile(Q5).Other determinants included hospitalization:prevalence ratio(PR)=2.8(95%CI:1.8-4.5)and delayed treatment:PR=1.5(95%CI:1.3-1.7).Protective factors included receiving care at a public health facility:PR=0.8(95%CI:0.6-1.0),and a higher body mass index(BMI):PR=0.97(95%CI:0.96-0.98).Pre TB expenditure,hospitalization and BMI were significant predictors in all sensitivity analysis scenarios.Conclusions::There are significant inequities in the occurrence of catastrophic costs.Social protection interventions in addition to existing medical and public health interventions are important to implement for patients most at risk of incurring catastrophic costs.
