Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With increasing rates of tuberculosis (TB) infection and disease worldwide, the rate of perinatal TB is also affected. A high index of suspicion by health professionals, in both the developed and developing world, is required to detect and manage tuberculosis in pregnancy and the early newborn period. Differences in immune responses in the fetus and neonate add to the diagnostic difficulties already recognised in young children. Although specific guidelines for the treatment of this potentially devastating disease are lacking due to paucity of experience, outcome is favourable, if the condition is recognised and treated according to existing TB protocols. HIV co-infection, multi- and extensively-drug resistant (MDR/XDR) TB contribute to the challenges. New diagnostic and vaccine developments hold future promise, but much work is needed to completely understand the complex immune responses to tuberculosis and control this disease.
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PMID:Perinatal tuberculosis: new challenges in the diagnosis and treatment of tuberculosis in infants and the newborn. 1882 26

The setting for this retrospective cohort study was a specialised tuberculosis unit in Madrid, Spain. The objective was to describe the risk factors for multidrug-resistant tuberculosis (MDR-TB). The medical records of all patients admitted to the unit were reviewed retrospectively to identify factors associated with multidrug resistance. Patients with positive culture for M. tuberculosis and with available drug-susceptibility tests were included. The variables assessed were age, gender, country of origin, homelessness, alcohol consumption, intravenous drug use, methadone substitution therapy, contact with a tuberculosis patient, sputum smear, site of disease, previous tuberculosis treatment, HIV infection, history of imprisonment, diabetes mellitus and chronic obstructive pulmonary disease. Thirty patients with MDR-TB and 666 patients with non-MDR-TB were included from the years 1997 to 2006. The only factors associated with MDR-TB in multivariate analysis were previous tuberculosis treatment (OR: 3.44; 95% CI: 1.58-7.50; p = 0.003), age group 45-64 years (OR: 3.24; 95% CI: 1.34-7.81; p = 0.009) and alcohol abuse (OR: 0.12; 95% CI: 0.03 to 0.55; p = 0.003). In our study, patients who had had previous treatment for tuberculosis, who were 45-64 years of age or who had no history of alcohol abuse were more likely to have MDR-TB.
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PMID:Risk factors for multidrug-resistant tuberculosis in a tuberculosis unit in Madrid, Spain. 1883 Jul 25

Active-site inhibitors of HIV-1 PR (protease) block viral replication by preventing viral maturation. However, HIV-1 often develops resistance to active-site inhibitors through multiple mutations in PR and therefore recent efforts have focused on inhibiting PR dimerization as an alternative approach. Dimerization inhibitors have been identified using kinetic analysis, but additional characterization of the effect of these inhibitors on PR by physical methods has been difficult. In the present study, we identified a PR(MDR) (multi-drug-resistant HIV-1 PR) that was highly resistant to autoproteolysis. Using this PR and a novel size-exclusion chromatographic approach that incorporated fluorescence and MS detection, we were able to demonstrate inhibition of dimerization using P27 (peptide 27), a peptide dimerization inhibitor of PR previously identified on the basis of kinetic analysis. Incubation of PR(MDR) with P27, or other dimerization inhibitors, led to a dose- and time-dependent formation of PR monomers based on the change in elution time by size exclusion and its similar elution time to engineered forms of monomeric PR, namely PR(T26A) and glutathionylated PR. In contrast, incubation of PR(MDR) with a potent active-site inhibitor did not change the elution time for the PR(MDR) dimer. The monomeric PR induced by P27 had fluorescent characteristics which were consistent with unfolded PR. Structure-activity studies identified the active regions of P27 and experiments were performed to examine the effect of other dimerization inhibitors on PR. The present study is the first characterization of dimerization inhibition of PR(MDR), a prime target for these inhibitors, using a novel size-exclusion chromatographic approach.
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PMID:Analysis and characterization of dimerization inhibition of a multi-drug-resistant human immunodeficiency virus type 1 protease using a novel size-exclusion chromatographic approach. 1914 65

Drug resistant tuberculosis is a man made problem. While tuberculosis is hundred percent curable, multidrug resistant tuberculosis (MDR-TB) is difficult to treat. Inadequate and incomplete treatment and poor treatment adherence has led to a newer form of drug resistance known as extensively drug resistant tuberculosis (XDR-TB). XDR-TB is defined as tuberculosis caused by Mycobacterium tuberculosis strain, which is resistant to at least rifampicin and isoniazid among the first line anti tubercular drugs (MDR-TB) in addition to resistance to any fluroquinolones and at least one of three injectable second line anti tubercular drugs i.e. amikacin, kanamycin and/or capreomycin. Mismanagement of tuberculosis paves the way to drug resistant tuberculosis. Emergence of XDR-TB is reported world wide. Reported prevalence rates of XDR-TB of total MDR cases are; 6.6% overall worldwide, 6.5% in industrialized countries, 13.6% in Russia and Eastern Europe, 1.5% in Asia, 0.6% in Africa and Middle East and 15.4% in Republic of Korea. Better management and control of tuberculosis specially drug resistant TB by experienced and qualified doctors, access to standard microbiology laboratory,co-morbitidy of HIV and tuberculosis,new anti-TB drug regimens, better diagnostic tests,international standards for second line drugs (SLD)-susceptibility testing,invention of newer anti- tubercular molecules and vaccines and knowing the real magnitude of XDR-TB are some of the important issues to be addressed for effective prevention and management of XDR-TB.
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PMID:Multidrug-resistant to extensively drug resistant tuberculosis: what is next? 1920 85

A total of 290 HIV/AIDS patients were recruited into this retrospective study, which was carried out at the National Tuberculosis Center (NTBC), Kuala Lumpur. The age range was 18 to 75 years with a mean age of 36.10 (SD +/- 7.44) years. Males outnumbered females by a ratio of 31:1. In this study, the majority of patients were male (96.9%), Malay (47.2%), single (66.9%), unemployed (81%), and smoked (61.4%). The main risk marker identified was injecting drug use (74.5%). The most common clinical manifestations were cough, fever, sputum, lymphadenopathy, and chest infiltrations. More than half of the patients (85.9%) were diagnosed with localized tuberculosis (pulmonary) and the others (14.1%) had extra-pulmonary or disseminated tuberculosis. At the time of this study, the majority of the patients (16.9%) had CD4 cell counts of less than 200 cell/mm3, with a median of 221 cell/mm3. Clinical outcomes demonstrated that among those who survived, 11.0% and 20.7% of the patients had completed treatment either > or = 6 or > or = 9 months, respectively, whereas 54.8% of patients were lost to follow-up, including 0.7% for MDR-TB. Diagnostic criteria for tuberculosis in this study were mainly clinical symptoms/signs and chest x-ray findings (31.0%).
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PMID:Tuberculosis: clinical manifestations and outcomes. 1923 68

The objective of this study was to observe the prevalence of drug resistance in Mycobacterium tuberculosis isolates in HIV associated tuberculosis co-infected patients in Phnom Penh City. The isolates of M. tuberculosis were collected during active laboratory-based surveillance. Of the 98 isolates studied, M. tuberculosis resistance to isoniazid was seen in 23.5%, resistance to rifampicin was seen in 16.3% and multidrug-resistance (MDR-TB) was seen in 5.1%. Our findings reveal an alarmingly high level of resistance to isoniazid and rifampicin, and confirms the need for drug susceptibility testing to guide treatment in patients with culture positive tuberculosis.
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PMID:Anti-tuberculosis drug resistance and HIV co-infection in Phnom Penh, Cambodia. 1932 41

Tuberculosis has remained an enemy of humankind since its inception. It has affected all facets of human life and remained leading cause of mortality and morbidity despite of availability of effective chemotherapy and BCG vaccine in 21st century. This has exposed the frailties of the current drug armamentarium. No new drug is available acting through novel mechanism of action for last 40 years. This has culminated into resistant strain of TB, MDR-TB and XDR-TB. Concomitant occurrence of TB and HIV presents a lethal combination. The availability of the M. tuberculosis genome sequence and mycobacterial genetic tools, such as transposon mutagenesis, gene knockout and gene transfer, greatly facilitate target identification. This review provides a comprehensive literature compilation on the present research paradigm of anti-TB drug discovery including advances in the new structural classes analogs reported in last decade.
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PMID:New frontiers in the therapy of tuberculosis: fighting with the global menace. 1935 20

Tuberculosis (TB) has a worthy reputation as one of the great mimickers in medicine with a multitude of clinical pictures and variations. Noncontiguous spinal TB is described as atypical and case reports are published as rarities in the mainstream academic journals. The aim of the study was to asses the incidence and review of the management of non-contiguous spinal TB. We identified 16 cases of noncontiguous spinal TB from a single surgeon series of 98 patients, who were managed surgically between 2001 and 2006. These were diagnosed on whole spine MRI. This represents the largest series reported in literature to date and is higher than the expected incidence. Case notes and imaging were retrospectively reviewed in an attempt to ascertain if there were any parameters to differentiate this group from the rest of the TB spine population. Our incidence of noncontiguous spinal TB is 16.3%. There was a higher incidence of neurology in the noncontiguous group (75%) compared to the rest of our group (58.5%). Non-contiguous TB was not found to be a manifestation of HIV, MDR TB or of chronicity in our series. Most noncontiguous lesions were evident on plain radiology. Noncontiguous spinal TB is common in areas of high prevalence such as South Africa. Despite being frequently missed initially, noncontiguous involvement is evident on plain radiography and simply requires a higher index of suspicion. When investigating spine TB patients, simple radiology of the entire spine is mandatory. If available, a full spine sagittal MRI is extremely useful in identifying noncontiguous lesions. Treatment of noncontiguous tuberculosis is as for standard spinal TB cases in our unit with similar outcomes, but care needs to be taken in surgical planning as patients may have multiple areas of neurological compromise.
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PMID:Noncontiguous spinal tuberculosis: incidence and management. 1935 78

Tuberculosis, due to its relentless nature, is now a major public health threat. The concomitant resurgence of TB with the MDR- or XDR-TB and HIV/AIDS pandemic has exposed the frailties of the current drug armatorium. Based on isosteric replacement and good 3D structural similarity between PA-824, a novel antimycobacterial agent undergoing clinical trials, and imidazo[1,2-c]pyrimidines, we have designed novel imidazo[1,2-c]pyrimidines. The designed molecules were synthesized by nucleophilic displacement of chloro group of various substituted 4-chloropyrimidines by ethanolamine followed by cyclisation of these 4-(2-hydroxyethyl)aminopyrimidines to imidazo[1,2-c]pyrimidines in good yield. All the compounds were screened for their antimycobacterial activity on Mycobacterium tuberculosis H37Rv strain by 1% proportion method. Some of the synthesized compounds exhibited potent antimycobacterial activity with MIC values in the range of 2-20 microg/mL.
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PMID:Design, synthesis and antimycobacterial activity of some novel imidazo[1,2-c]pyrimidines. 1942 96

The paper compares the response of the South African Government to HIV and AIDS with the government's policy development concerning the use of tobacco. The high burden of disease from HIV and AIDS in South Africa and the morbidity and mortality from the use of tobacco are outlined. Using the framework of the Ottawa Charter for Health Promotion, the paper reviews and critiques the Government's different stance to building public policy, creating supportive environments, engaging community participation, developing personal skills and re-orienting the health services, for HIV/AIDS and tobacco. The result of these policy choices is described. The lack of adequate implementation of the key elements of the Ottawa Charter has resulted in high morbidity and mortality due to the spread of HIV infection in South Africa. This has also influenced the resurgence of tuberculosis, and the accompanying MDR and XDR TB epidemics. The high prevalence of HIV infection has also meant that the health system is unable to cope with the large numbers of patients requiring anti-retroviral treatment, and the early morbidity and mortality of young economically active people has had devastating social consequences, resulting in the large numbers of orphans. In contrast, South Africa is a signatory to the World Health Organizations' Framework Convention on Tobacco Control, and has successfully implemented many of the policies.
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PMID:Meeting the challenges of the Ottawa Charter: comparing South African responses to AIDS and tobacco control. 1952 5


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