Microbiological infections in HIV positive Bahraini patients with low CD4+ T-lymphocyte count

The correlation of CD4+ T-lymphocyte count and the distribution of pathogenic or opportunistic microbial infection most commonly found in HIV positive individuals differ from one area to the other. The present study reports such findings in 67 HIV positive Bahraini patients in the period May 1997 to Nov. 1998. CD4+ T-lymphocyte count was measured using flow cytometry. Bacterial and fungal cultures were performed. Serological diagnosis was performed when indicated. Viral study was done serologically. The distribution of CD4+ T-lymphocyte count in the studied group was: 21 patients (31.3%) less than 100 cells/microl, 5 patients (7.5%) 100-200 cells/microl, 25 patients (37.3%) 201-500 cells/microl and 16 patients (23.9%) with count more than 500 cells/microl. Among patients with low CD4 count (less than 100 cells/microl) (n=21), microbial infections varied from fungal infections 66%, bacterial infections 57% and viral infections 4.8%. Bacterial infections included Salmonellosis (14.3%), Staphylococcus epidermidis (14.3%), Pseudomonas aeruginosa (9.5%), H. influenzae (9.5%), Legionellosis (4.8%) and E. coli (4.8%). Fungal infection included Candida albicans (52.4%), Pneumocystis carinii (9.5%), Cryptococcus neoformans (4.8%). Viral infection included H. simplex to (4.8%). Fungal infections were the highest common infection in thus study. The most common microbial infection was Candida albicans. P. carinii and Cryptococcus neoformans were less common than found in other studies world wide.     

Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intolerance to imatinib

Background

Dasatinib 100 mg once daily achieves intermittent BCR-ABL kinase inhibition and is approved for chronic-phase chronic myeloid leukemia patients resistant or intolerant to imatinib. To better assess durability of response to and tolerability of dasatinib, data from a 2-year minimum follow-up for a dose-optimization study in chronic-phase chronic myeloid leukemia are reported here.

Design and Methods

In a phase 3 study, 670 chronic-phase chronic myeloid leukemia patients with resistance, intolerance, or suboptimal response to imatinib were randomized to dasatinib 100 mg once-daily, 50 mg twice-daily, 140 mg once-daily, or 70 mg twice-daily.

Results

Data from a 2-year minimum follow-up demonstrate that dasatinib 100 mg once daily achieves major cytogenetic response and complete cytogenetic response rates comparable to those in the other treatment arms, and reduces the frequency of key side effects. Comparable 2-year progression-free survival and overall survival rates were observed (80% and 91%, respectively, for 100 mg once daily, and 75%–76% and 88%–94%, respectively, in other arms). Complete cytogenetic responses were achieved rapidly, typically by 6 months. In patients treated with dasatinib 100 mg once daily for 6 months without complete cytogenetic response, the likelihood of achieving such a response by 2 years was 50% for patients who had achieved a partial cytogenetic response, and only 8% or less for patients with minor, minimal, or no cytogenetic response. Less than 3% of patients suffered disease transformation to accelerated or blast phase.

Conclusions

Intermittent kinase inhibition can achieve rapid and durable responses, indistinguishable from those achieved with more continuous inhibition.     

Heme oxygenase-1-generated biliverdin ameliorates experimental murine colitis

BACKGROUND: Heme oxygenase-1 (HO-1) seems to have an important protective role in acute and chronic inflammation. The products of heme catalysis, biliverdin/bilirubin, carbon monoxide (CO), and iron (that induces apoferritin) mediate the beneficial effects of HO-1. Blockade of HO-1 activity results in exacerbation of experimental colitis. We tested whether HO-1 has protective effects in the development of colitis and determined that specific enzymatic products of HO-1 are responsible for these effects. METHODS: Colitis was induced by oral administration of dextran sodium sulfate (5%) to C57BL/6 mice for 7 days. HO-1 was up-regulated by cobalt-protoporphyrin (5 mg/kg, intraperitoneally). Biliverdin, exogenous CO, or the iron chelator desferrioxamine was administered to other groups. RESULTS: Cobalt-protoporphyrin treatment resulted in significant up-regulation of HO-1 protein in mucosal and submucosal cells. Induction of HO-1 was associated with significantly less loss of body weight in mice with induced colitis (-12% versus -22% in the control animals, P < 0.001). Development of diarrhea and gastrointestinal hemorrhage was substantially delayed in animals in which HO-1 was induced, and mucosal injury was significantly attenuated. Administration of CO or desferrioxamine alone had no significant effects, whereas enhanced protection with lesser evidence of bowel inflammation was observed with systemic biliverdin administration (50 micromol/kg, 3 times per day, intraperitoneally). CONCLUSIONS: We conclude that heightened HO-1 expression or administration of biliverdin ameliorates dextran sodium sulfate-induced experimental colitis. Novel therapeutic strategies based on HO-1 and/or biliverdin administration may have use in inflammatory bowel disease.     

Smoking prevention and cessation in the Africa and Middle East region: a consensus draft guideline for healthcare providers--executive summary

Despite the abundance of scientific evidence confirming the health consequences of smoking and other forms of tobacco use, the tobacco epidemic remains an important public health problem and by 2030 it is predicted that more than 80% of tobacco deaths will be in developing countries. In Africa and the Middle East, many local factors contribute to the initiation and maintenance of tobacco use. Although efforts to reduce the mortality and morbidity associated with smoking and tobacco dependence are underway, there is a need for guidance on how to utilize appropriate tobacco control policies and psychology- and pharmacology-based therapies to counter tobacco dependence as recommended by the Framework Convention on Tobacco Control (FCTC). A group of tobacco cessation experts from public health services and/or academic institutions in Africa and the Middle East participated in a series of four meetings held in Cairo, Cape Town, and Dubai between May 2008 and February 2011 to develop a draft guideline tailored to their region. This article provides the background to the development of this draft smoking cessation guideline and discusses how the recommendations can be implemented and progress monitored to promote both primary prevention and cessation of tobacco use within our countries. The draft guideline for Africa and the Middle East provides an important resource in combating the devastating effects of tobacco use in these regions which can be further localized through engagement with local stakeholders in the countries of the region.     

Satisfaction with and adherence to warfarin treatment: A cross-sectional study among Sudanese patients

Background

Satisfaction with and adherence to oral anticoagulant treatment are important measures that decrease morbidity and mortality. Higher satisfaction and adherence to warfarin therapy was found to be associated among other factors with good International Normalized Ratio (INR) control.

Small changes in enzyme function can lead to surprisingly large fitness effects during adaptive evolution of antibiotic resistance

In principle, evolutionary outcomes could be largely predicted if all of the relevant physicochemical variants of a particular protein function under selection were known and integrated into an appropriate physiological model. We have tested this principle by generating a family of variants of the tetracycline resistance protein TetX2 and identified the physicochemical properties most correlated with organismal fitness. Surprisingly, small changes in the K_m(MCN), less than twofold, were sufficient to produce highly successful adaptive mutants over clinically relevant drug concentrations. We then built a quantitative model directly relating the in vitro physicochemical properties of the mutant enzymes to the growth rates of bacteria carrying a single chromosomal copy of the tet(X2) variants over a wide range of minocycline (MCN) concentrations. Importantly, this model allows the prediction of enzymatic properties directly from cellular growth rates as well as the physicochemical-fitness landscape of TetX2. Using experimental evolution and deep sequencing to monitor the allelic frequencies of the seven most biochemically efficient TetX2 mutants in 10 independently evolving populations, we showed that the model correctly predicted the success of the two most beneficial variants tet(X2)_T280A and tet(X2)_N371I. The structure of the most efficient variant, TetX2_T280A, in complex with MCN at 2.7 Å resolution suggests an indirect effect on enzyme kinetics. Taken together, these findings support an important role for readily accessible small steps in protein evolution that can, in turn, greatly increase the fitness of an organism during natural selection.     

Dental patient awareness of smoking effects on oral health: Comparison of smokers and non-smokers

OBJECTIVES: The negative effects of cigarette smoking on oral health are well established, yet few studies assessed patient awareness of such effects. The aim of this study was to examine differences in dental patient knowledge and awareness of the effects of smoking on oral health between smokers and non-smokers. METHODS: Adult patients from 12 dental centers in Kuwait were asked to complete a 14-point self-administered structured questionnaire on the effects of smoking on oral health in this cross-sectional survey. Significant associations between oral health knowledge, smoking status, and sociodemographic variables were examined with univariate analysis and logistic regression. RESULTS: A total of 1012 subjects participated (response rate = 84.3%). The prevalence of smoking was 29.3%. Fewer smokers than non-smokers thought that oral health and smoking are related (92.2% vs. 95.8%; P = 0.020), and that smoking affected oral cancer (52.4% vs. 66.8%; P < 0.001), periodontal health (72% vs. 78%; P = 0.040), or tooth staining (86.1% vs. 90.9%; P = 0.018). Logistic regression analysis showed smokers to be significantly less aware of the oral health effects of smoking than non-smoking patients (OR=1.51; 95% CI: 1.05-2.16; P = 0.025). CONCLUSION: Smoking dental patients are significantly less aware of the oral health effects of smoking than non-smokers. Comparative studies in other populations may be warranted to ascertain the validity of these results.     

Self-inflicted midline facial gunshot wounds: the case for a combined craniofacial and microvascular team approach.

Self-inflicted gunshot wounds to the face are extremely complex and difficult to manage. In the past, these patients have been treated by debridement, hemostasis, and soft tissue closure with reconstruction deferred to a later time. This approach consigned the patient to significant facial contracture and scarring, which is impossible to adequately correct secondarily. As a result of this traditional approach, patients had substantial disfigurement as well as dysfunction. At the Medical College of Wisconsin, we have begun an aggressive multispecialty team approach in which the maximum possible reconstruction is performed acutely. This has resulted in superior aesthetic and functional results, and in a substantially lower number of hospitalizations, surgical procedures, and hospital days. This approach includes the spectrum of current plastic surgical techniques including the craniofacial approach using open reduction with accurate miniplate reconstruction and acute bone grafting as well as soft tissue reconstruction and replacement using composite multiple-stacked free tissue transfer. We believe the overall approach provides a superior result and we will continue a program of aggressive and acute intervention.