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Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
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Target Concepts:
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Query: UMLS:C0019693 (
HIV
)
170,526
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Management of active TB requires a team approach. All patients newly diagnosed with TB should be tested for
HIV infection
. Currently available anti-TB drug regimens are well tolerated and highly effective. Directly observed therapy has shown improved survival and decline in the rate of new cases of active TB. In suspected or proven drug-resistant TB, the regimen should be individualized in consultation with a specialist experienced in
MDR
TB. Primary care physicians play a pivotal role in reducing morbidity and emergence of drug resistance through early diagnosis and prompt initiation of an effective regimen under directly observed therapy.
...
PMID:Management of tuberculosis. Choosing an effective regimen and ensuring compliance. 1095 47
The classic molecular biology methods like Northern or Southern blot analyse non-amplified DNA or RNA, but need large amounts of nucleic acids, in many instances from tissues or cells that are heterogeneous. In contrast, polymerase chain reaction (PCR)-based techniques allow us to obtain genetic information through the specific amplification of nucleic acid sequences starting with a very low number of target copies. These reactions are characterized by a logarithmic amplification of the target sequences i.e. increase of PCR copies followed by a plateau phase showing a rapid decrease to zero of copy number increment per cycle. Accordingly, the amount of specific DNA product at the end of the PCR run bears no correlation to the number of target copies present in the original specimen. However, many applications in medicine or research require quantification of the number of specific targets in the specimen. This has generated a rapidly increasing need for the development of quantitative PCR techniques. Prominent examples are the determination of viral load in blood specimens for the diagnosis of
HIV
or HCV infections, the determination of changes in gene dosage through amplification or deletion e.g. of
MDR
-1, erb-B2, c-myc or the loss of heterozygosity in general. Finally, the analysis of gene expression on the mRNA level does require quantitative approaches to reverse transcriptase PCR, e.g. for studies in morphogenesis or the profiling of cancer cells. Recent advances in technology allow detection of the increment per cycle of a specifically generated PCR product in "real-time mode". Together with the new powerful methods to dissect heterogeneous tissues or fractionate bodily fluids, this now sets the stage for a detailed analysis not only of the genes and genetic changes within a single cell, but also of the use such cell makes of its genes e.g. in pharmacogenomics. Examples of recent developments of the technology and their applications will be given.
...
PMID:Quantitative PCR. 1109 36
Derivatives of piperidinylethyl, phenoxyethyl and fluoroethyl bromopyridyl thioureas were designed and synthesized as non-nucleoside reverse transcriptase inhibitors (NNRTIs) of
HIV
-1 reverse transcriptase (RT). The anti-
HIV
activity of these compounds was examined by determining their ability to inhibit the replication of the
HIV
-1 strain HTLV(IIIB) in human peripheral blood mononuclear cells. The unsubstituted parent pyridyl thiourea compound N-[2-(1-piperidine)ethyl]-N'-[2-(pyridyl)] thiourea (1) exhibited no anti-
HIV
activity, even at 100 microM. However, the thiourea derivatives that contain a bromo- or chloro-substituted pyridyl group, compounds 2 and 5, inhibited
HIV
-1 replication at nanomolar concentrations. The addition of a methyl group onto the piperidine ring significantly altered the potency of these compounds; while methyl substitution at the 3-position of the piperidine ring reduced the activity, methyl substitution at the 2-position enhanced the anti-
HIV
activity. The IC50 value of the lead piperidinyl compound, N-[2-(2-methylpiperidinylethyl)]-N'-[2-(5-bromopyridyl)] thiourea (4) was <0.001 microM. All three phenoxyethyl derivatives, including the unsubstituted parent phenoxyethyl pyridyl thiourea compound N-[2-(phenoxy)ethyl]-N'-[2-(pyridyl)]thiourea (8) and the bromo-/chloro-substituted phenoxyethyl halopyridyl thiourea compounds N-[2-(phenoxy)ethyl]-N'-[2-(5-chloropyridyl)]thiourea (9) and N-[2-(phenoxy)ethyl]-N'-[2-(5-bromopyridyl)]thiourea (10) exhibited potent anti-
HIV
activity with nanomolar IC values. The corresponding fluoroethyl halopyridyl thiourea compounds beta-fluoro[2-phenethyl]-N'[2-(5-chloropyridyl)]thiourea (11) and beta-fluoro[2-phenethyl]-N'[2-(5-bromopyridyl)]thiourea (12) inhibited
HIV
-1 replication in PBMC with subnanomolar IC50 values and selectivity indices >30000. Compared to the corresponding phenoxyethyl thiourea compounds 9 and 10, these compounds were >4-5-fold more active as anti-
HIV
agents. Notably, the lead fluorothiourea compounds 11 and 12 were both substantially more active against the NNRTI-resistant
HIV
strains RT-
MDR
(V106A) and A17 (Y181C) than nevirapine or delavirdine. Taken together, our results provide additional experimental evidence that the structural features of the 'linker unit' between the pyridyl and phenyl moieties and changes in the phenyl group of PETT-related thiourea compounds significantly affects their biological activity as NNRTIs of
HIV
-1 RT.
...
PMID:Piperidinylethyl, phenoxyethyl and fluoroethyl bromopyridyl thiourea compounds with potent anti-HIV activity. 1114 31
Results of two studies at hospitals in New York City have shown how early diagnosis, proper treatment, and directly observed therapy (DOT) can improve survival of AIDS patients with multidrug-resistant tuberculosis (MDR-TB). The first study followed ten patients and included early diagnosis, treatment with an initial regimen of four-drug therapy, rapid susceptibility testing, and subsequent
MDR
-TB treatment with DOT. After more than a year of follow-up, nine of the ten patients had been discharged with negative cultures. The other patient died before
MDR
-TB could be started. All the patients were given initial therapy of four drugs--isoniazid (INH), rifampin, pyrazinamide, and ethambutol. The nine patients are still on drug therapy, but the question remains when, if at all, the patients should discontinue treatment. The second study followed 50 patients--45
HIV
-positive, 5
HIV
-negative--for more than 3 years. More than half of the patients who responded to therapy survived for one year. Of the 24
MDR
-TB patients who have responded to treatment, 8
HIV
-positive patients relapsed. Little correlation was found between relapse and CD4 count, although patients who had an opportunistic infection prior to TB infection were more likely to relapse.
...
PMID:Prolonging survival among MDR-TB AIDS patients. 1136 56
P-glycoprotein is a product of the multidrug resistance (
MDR
-1) gene. In non-Hodgkin's lymphoma, less than 20% of untreated de novo lymphomas express
MDR
-1 compared with approximately 50% after failure of chemotherapy. We wished to study the expression of
MDR
-1 in AIDS-related non-Hodgkin's lymphoma (AIDS-NHL). Tissue biopsies from 50 patients with newly diagnosed AIDS-NHL were studied by immunohistochemical analysis using C494, a monoclonal antibody specific for the
MDR
-1 isoform of P-gp.
MDR
-1 expression was correlated with patient demographics, lymphoma characteristics, response to chemotherapy, and survival. Forty-six males and four females with a median age of 38 years (range 26-63) were studied. A prior AIDS-defining opportunistic infection was reported in 35 patients (70%). The median CD4+ lymphocyte count was 69/mm(3) (range 0-920). Thirty-two patients (63%) had received prior anti-
HIV
therapy, including a protease inhibitor in five (10%). Pathologic types consisted of diffuse large cell in 13 (26%), immunoblastic in 13 (26%), small non-cleaved in 22 (44%), and high grade not otherwise specified in two (4%). The majority of patients (76%) had stage III/IV disease. Pre-treatment lymphoma tissues from 33 patients (66%) stained positively for
MDR
-1.
MDR
-1 positive patients had a significantly lower complete remission rate compared to
MDR
-1 negative patients (33 versus 65%, P=0.042). Duration of complete response was significantly longer in
MDR
-1 negative patients compared with
MDR
-1 positive patients (not reached versus 9.9 months, P=0.003). Strategies to overcome
MDR
-1 expression may be important for initial treatment in patients with AIDS-NHL.
...
PMID:Multidrug resistance (MDR-1) expression in AIDS-related lymphomas. 1175 62
In the 1990s, outbreaks of multidrug-resistant tuberculosis (
MDR
TB) among
HIV
-positive patients ultimately led to the establishment in the developed world of a comprehensive TB control strategy for these patients that is effective. The treatment regimen for
HIV
and
MDR
TB is complicated by the fact that most of the drugs used have not been studied for interactions with antivirals. Hence, overlapping toxicities require intensive management and monitoring of these patients. Good public health policy is essential to preventing
MDR
TB outbreaks among immunosuppressed patients.
...
PMID:Multidrug-resistant tuberculosis and HIV infection. 1179 12
India has the highest number of tuberculosis cases of any country in the world, and many of these cases are
MDR
TB. A combination of contributing factors has led to the current public health crisis: a failing National Tuberculosis Programme, denial and lack of compliance on the part of patients, lack of regulation of doctors in private practice, governmental policy failure and corruption, social and economic problems, and a growing
HIV
epidemic. This situation must be combatted on several fronts, including promoting social change; increasing government funding; seeking global aid; implementing DOTS, non-DOTS, and NGO programs; integrating TB and
HIV
programs; funding research; enacting regulatory legislation; and establishing continuing medical education programs among private practitioners.
...
PMID:India's multidrug-resistant tuberculosis crisis. 1179 27
This modest study is trying to surprise the clinic shades spectrum of the pulmonary tuberculosis met at adults in the Romanati Plain zone, which was high consumption at the end of the second millennium without avoiding the new tones which AIDS and the
MDR
-TB brought. This things determined people to speak about the "NEW TUBERCULOSIS" of the third millennium. It had started from a number of 393 patients suffering from pulmonary tuberculosis and age over twenty. This people were in hospital between 1997-2000 at the Pneumophysiology section in the Caracal's Municipal hospital. They were grouped after this parameters: the disease type, sex, environment, occupation, beginning form, clinic form, bacteriologic exam BK, diagnosis delay, lesion stretch and associated diseases, looking to discover the profile which is the most frequently used which satisfies in high percentage many of the studied parameters. We underline that the
HIV
test was negative to all the new cases and readmitted positive at T3 and to all the sick people who were registered with therapeutic failure in 1997 and 1999, so the AIDS impact with tuberculosis in this zone was null. Also systematic in the last two years we made ABG at relapses, failures and chronic; the bacillus resistance was not put in evidence, thing also hard to accept. The profile the most frequently met no matter the environments life, disease type, sex, age is the fibro-cases-cavitary farm (50%) followed by the infiltrative one (35%) with an "classic" onset in more than two third of the cases, bilaterally of the injures and the diagnosis delay with at least two months at 60% from all cases and a positively of the sputum in microscopy of about 50%. At least one third of the sick people are unemployed. This profile has of course epidemic consequences an therapeutic especially.
...
PMID:[Clinical forms of pulmonary tuberculosis in adults in the Romanati Plains at the change of millennium]. 1204 72
There has been limited detailed epidemiological data available on tuberculosis in the Republic of Ireland. The 1998 and 1999 National TB Reports produced by the National Disease Surveillance Centre presented disaggregate national data describing in detail the epidemiology of TB in the Republic of Ireland. Individual case notifications were collated by health boards, forwarded to NDSC where they were entered onto a national TB database and then analysed using Epi-Info. There were 893 cases of TB notified in 1998-1999. It was more common in older age groups and men. 50% of cases occurred in those less than 45 years, an indication of considerable ongoing transmission of tuberculosis. Regional variation in the rate of TB exists and a relatively small proportion of cases occurred in foreign-born patients. TB in
HIV
positive patients was not common and
MDR
-TB has also been observed. TB has not disappeared from the Republic of Ireland. Treatment, contact tracing and surveillance need to be maintained and preferably enhanced.
...
PMID:Tuberculosis in the Republic of Ireland at the end of the 1990s. 1209 93
Tuberculosis (TB) has recently re-emerged as a major public health problem in Thailand. As a consequence of the
HIV
epidemic in the country, the TB burden has been rising in terms of both morbidity, and mortality which have tremendous socioeconomic impact. However, a study of the cost of various anti-TB drugs in Thailand has never been conducted. A specific aim of this study was to compare the total provider costs of delivering services to different types of TB patient in four zonal TB centers located in the east, northeast, north, and south of Thailand. This aim was accomplished by calculating the unit costs of TB treatment services at these TB centers during the year 1996-1997. All units of the zonal TB centers were classified into 5 cost-center categories: treatment units, laboratory units, radiology units, pharmaceutical units, and administrative/supportive units. The results showed that the average total provider cost of multidrug resistant TB (
MDR
TB) patients was 89,735.49 baht which was the highest of any type of patient and was 17 times higher than the cost of smear-negative TB cases; this finding was attributed to the high cost of anti-TB drugs for
MDR
TB cases (65,870 baht), some 95 times higher than the cost for smear-negative cases. Total provider costs were highest in the northeastern region TB centers and lowest in the southern centers for every type of TB patient: smear-negative TB cases (7.727 baht vs 3.916 baht). newly smear positive TB cases (12,539 baht vs 7.020 baht), TB with AIDS cases (15,108 baht vs 8,369 baht). re-treatment TB cases (16,679 baht vs 9,696 baht), and
MDR
TB cases (102.330 baht vs 82,933 baht). The information from this study may be useful when reviewing the role, function, and cost structure of each TB center in Thailand in order to establish a strategic plan for effective TB control.
...
PMID:Cost analysis of different types of tuberculosis patient at tuberculosis centers in Thailand. 1223 32
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