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)

A 49-year-old Japanese male who had been imprisoned for five years then lived with other men complained of fever, constitutional symptoms and a 12 kg weight loss over four-month period. He was referred to us as his gastric washings were positive for acid-fast bacilli (AFB). Chest X-ray showed patchy, infiltrative small shadows primarily in the right upper lung field without hilar adenopathy. Before transfer to our hospital, tuberculosis chemotherapy composed of SM, INH, RFP and PZA was initiated. Over the next three weeks, fever dropped, and the above described abnormal shadows on the chest X-ray improved, leaving small cystic lesions. Although a sputum smear was negative for AFB, M. tuberculosis was isolated from cultured samples and sensitive to all standard anti-tuberculous drugs. AFB were also demonstrated on a touch imprint of biopsied cervical lymph nodes. Sputum samples turned negative one month later both on smear and culture. Moreover, high fever developed and another abnormal shadow indicative of Pneumocystis carinii (PCP) appeared in the left lung field one month after the admission. White plaque was noted in the oral cavity. Dark red nodules were observed on the upper extremities and chest wall, and diagnosed histologically as Kaposi's sarcoma. Serologic testing for HIV was positive both by PA and Western blot methods, thus AIDS was diagnosed according to the CDC surveillance case definition for AIDS with the diagnosis of tuberculosis. The patient died of wasting syndrome on the 90th hospital day. On autopsy, small thin-walled cavities were observed in the right upper lung, correlating with earlier X-ray and CT findings.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case report of the atypical tuberculosis associated with AIDS]. 756 52

The number of cases with tuberculosis is again increasing in many countries, and recently several nosocomial outbreaks of multidrug-resistant tuberculosis have occurred in the United States. The number of patients with disseminated Mycobacterium avium complex (MAC) infections in AIDS population, and patients with MAC pulmonary disease unassociated with HIV seem to be also increasing. It takes at least 6 to 9 months for an initial treatment of active tuberculosis due to drug-sensitive strains with the standard regimen which includes isoniazid (INH) and rifampicin (RFP). Treatment for the diseases caused by drug-resistant M. tuberculosis and MAC is much more time-consuming and more toxic than for the diseases caused by drug-sensitive strains, and often unsuccessful. For the reasons described above, the developments of new agents with potent antimycobacterial activities are highly desired. The new agents should also be useful for treating patients who have acquired resistance to many of the currently available drugs. In this review the new antimycobacterial drugs are summarized. Some of them have already been used clinically, but many are still in experimental evaluations. 1) Rifamycin derivatives: rifabutin (RBT), KRM-1648 (KRM), rifapentin (RPT), FCE-22250, FCE-22807, CGP-7040, SPA-S-565 and other rifamycin derivatives. New rifamycin derivatives including RBT, KRM have increased in vitro antimycobacterial activities. RBT and KRM are much more active in vitro and in vivo than RFP against both M. tuberculosis and MAC. KRM seems to be more potent than RBT against MAC in experimental studies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[New drugs against tuberculosis and nontuberculous mycobacterial infections: a review]. 783 25

A retrospective cohort analysis of TB patients in the Canton of Zurich was undertaken to evaluate the effectiveness of a primary care physician-based tuberculosis treatment program in the Canton of Zurich (1991-1993) and compare it with treatment results in selected patient groups in controlled prospective studies. Of the 440 TB patients (62.5% men, 51% foreign born, 9.6% with HIV infection) 65% were initially hospitalized. The total treatment duration was 210 (+/-108) days on average. Only 75% of the patients who were treated by a total of 410 hospital and primary care physicians were treated with standard regimens according to guidelines. 3 patients were treatment failures; 13 relapsed (5.1% of the 257 patients reexamined in 1995). Possible causes for relapses were poor patient compliance due to alcoholism, homelessness, drug addiction, psychiatric disorders; prescription errors with inadequate treatment durations, concurrent AIDS disease, or use of a three-drug combination despite primary drug resistance. In 4 of the relapse patients and in all 3 treatment failures, secondary drug resistance developed under treatment. 5 of these 7 patients were treated initially only with a fixed three-drug regimen (Rifater). The relatively high INH resistance rate (8.6%) and relapse rate (5.1%) in the Canton of Zurich renders the use of a four-drug combination therapy necessary. In the outpatient maintenance phase, more effort must be devoted to ensuring patient compliance and adherence to a proper treatment duration. This should be documented by a standardized questionnaire at 6 or 12 months after initiation of therapy. In high risk patients in particular, home care visits by a TB nurse in addition to consultations by primary care physicians are necessary to ensure directly observed therapy (DOT) in order to prevent relapses and treatment failures.
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PMID:[Tuberculosis therapy in canton Zurich 1991-1993: what are the causes for recurrence and therapy failure?]. 899 25

The recent decrease of the number of tuberculosis patients in Japan, by the economical development and the establishment of standard regimen with INH, RFP, SM/EB and PZA, have brought decrease of concern to tuberculosis not only in the masses but also in the medical personnel, and the worsening of the medical economy by the advancing of the ages in the nations is forcing to close the tuberculosis wards. On the other hand, the recent situation of tuberculosis in Japan, such as the increase of HIV infection, the additional inflow of the foreign tuberculosis patients, the increase of tuberculosis patients in the younger population by the increase of mass-infection, and recent progress of the maldistributions of the tuberculosis patients realized the efforts of the education and training for tuberculosis to the medical students and medical personnel, even in the increase of items that they must learn. The Japanese Society for Tuberculosis set a Symposium "How Tuberculosis be Taught in Medical Education" in 1986. It will be worth to have Round Table Discussion concerning to the education and training for the tuberculosis, after 11 years. Doctor Sato from Nagoya City University reported as follows. To survey the actual condition of tuberculosis education before graduation, a nationwide medical school questionnaire survey was carried out. Answers were received from 80 institutions (100%). It was found that 58 institutions (72%) lacked tuberculosis ward. When the results from this survey, in the area of medical school lecture, were compared to the previous survey of 11 years ago, it showed a decrease in the time and frequency that tuberculosis covered during lecture. This tendency was clearly seen, with the exception of internal medicine, in surgery, in plastic surgery, in urology and in public health. Furthermore, medical schools lacking tuberculosis ward were found to have a lesser percentage of clinical lectures and bed-side teaching when compared to ones with tuberculosis ward. He concluded that in the medical school without tuberculosis ward, the tuberculosis education is virtually impossible, and it is necessary to carry out with hospitals that have tuberculosis ward. Doctor Honda from Sapporo Medical University reported that in the University Hospital, the Third Department of Internal Medicine holds 6 isolation sick-beds for tuberculosis (3 for men and 3 for women) which containing an exclusive day room and bath room, in 52 beds alloted to their department. They always give 2 or 3 lectures about tuberculosis to medical students and also give bed-side teaching using these beds. He concluded education on tuberculosis is necessary for the protection of doctor's delay, and the tuberculosis ward in the university is very useful in the education of tuberculosis to medical students, even the economical efficiency of these beds are low. Doctor Nakabayashi from Sapporo National Hospital reported that his hospital is a general hospital with 513 beds but has no tuberculosis-bed, and that this hospital is combined with Hokkaido Cancer Center and 91.7% of in-patients of pulmonary division are lung cancer and one or two residents are trained in pulmonary division by 6 months rotation. He also reported that in his hospital, 18 mycobacteria positive cases were treated through 1996, however the training for tuberculosis to residents are mainly by the differential diagnosis of tuberculosis with lung cancer through case conferences with staff doctors. Doctor Yosikawa from Daido Hospital reported as follows. In his hospital, tuberculosis-beds and other respiratory-beds are in the same nursing unit managed with the same standard for nursing, although tuberculosis-beds are separated from other respiratory-beds by door and have exclusive toilets and bath-room. The doctors could study general respiratory diseases and tuberculosis at the same time. Thirteen doctors have finished this training, and all of them could deepen their knowledge to tuberculosi
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PMID:[Education and training for tuberculosis in medical schools and in hospitals]. 949 41

Rifamycin drugs (i.e., rifampin, rifabutin, and rifapentine) are essential for short-course chemotherapy in persons with active tuberculosis (TB). However, adverse drug-drug interactions complicate the concurrent use of rifamycins and protease inhibitor drugs in persons with active TB who also are infected with human immunodeficiency virus (HIV-TB). CDC has recommended use of rifabutin in place of rifampin in multidrug regimens for the treatment of active TB in HIV-TB because rifabutin can be administered with antiretroviral treatment regimens that include protease inhibitors (1,2). These recommendations included twice-weekly intermittent therapy. Because intermittent rifabutin-based regimens had not been evaluated in clinical trials of HIV-TB, CDC's TB Trials Consortium (TBTC) initiated TBTC Study 23, a single-arm trial of twice-weekly rifabutin-based therapy for treatment of HIV-TB.
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PMID:Acquired rifamycin resistance in persons with advanced HIV disease being treated for active tuberculosis with intermittent rifamycin-based regimens. 1192 92

Tuberculosis (TB) is a growing international health concern, since it is the leading infectious cause of death in the world today. Moreover, the resurgence of TB in industrialized countries and the worldwide increase in the prevalence of Mycobacterium avium complex (MAC) infections in immunocompromised hosts have prompted the quest for new antimycobacterial drugs. In particular, the appearance of multidrug-resistant (MDR) strains of M. tuberculosis, which exhibit in vitro resistance to at least two major antituberculous drug (usually INH and RFP) and cause intractable TB, has greatly contributed to the increased incidence of TB. Because of the global health problems of TB, the increasing rate of MDR-TB and the high rate of a co-infection with HIV, the development of potent new antituberculous drugs without cross-resistance with known antimycobacterial agents is urgently needed. In this article, I reviewed the following areas. First, I briefly reviewed some new findings (mainly reported after 2000) on the pharmacological status of rifamycin derivatives (rifabutin, rifapentine, and rifalazil), fluoroquinolones (ciprofloxacin, ofloxacin, sparfloxacin, levofloxacin, gatifloxacin, sitafloxacin, moxifloxacin, and others), and new macrolides (clarithromycin, azithromycin, and roxithromycin). Second, I described other types of agents which are being developed as antimycobacterial drugs. Some of the agents discussed are already under preliminary clinical investigation, and others appear to be promising candidates for future development. In this review, the status of the development of new antimycobacterial, especially antituberculous agents including oxazolidinone (PNU-100480), 5'-nitroimidazole (CGI 17341), 2-pyridone (ABT-255), new riminophenazines, nitroimidazopyran (PA-824), new ketolides (ABT-773, telithromycin) and defensins (human neutrophil peptide-I), was examined. Third, the development of new antitubercular drugs was discussed according to the potential pharmacological target. New critical information on the whole genome of M. tuberculosis recently elucidated and increasing knowledge on various mycobacterial virulence genes will promote the progression in the identification of genes that code for new drug targets. Using such findings on mycobacterial genomes, drug development using quantitative structure-activity relationship may be possible in the near future. In this review, I described the screening of drugs that have an inhibitory activity against dTDP-rhamnose synthesis of M. tuberculosis, as a new drug target of the organism. In addition, I discussed the usefulness of antisense oligo DNAs specific to mycobacterial genes encoding certain metabolic enzymes or virulence factors that play roles in the bacterial escape from antimicrobial mechanisms of host macrophages. Fourth, I reviewed the drug vehicles which enable efficacious drug delivery to their target in vivo. The usefulness of poly (DL-lactide-co-glycolide) microsphere technology, which enables the encapsulated drugs to deliver the requested doses of them for prolonged time periods by a single shot without causing any toxicity and, moreover, enables the highly targeted delivery of the drugs to host macrophages, was discussed. Fifth, I described adjunctive immunotherapy for the management of patients with mycobacterial infections by giving certain immunomodulators in combination with antimycobacterial drugs. Adjuvant clinical trials using IL-2 or GM-CSF have been found to be efficacious to some extent in improving patients with tuberculosis or disseminated MAC infections. However, it seems that these immunopotentiating cytokines as well as IFN-gamma and IL-12 are not so promising for the therapeutic agents of mycobacterial infections because of the possible induction of immunosuppressive cytokines during adjuvant therapy and, in some cases, severe side-effect. Thus, the development of new classes of immuno-modulators other than cytokines, particularly those with no severe side-effect, is needed. This review dealt with ATP and its analogues which potentiate macrophage antimycobacterial activity via a purinergic P2X7 receptor. Finally, I described the roles of type II alveolar epithelial cells in the establishment of mycobacterial infections in the host lungs and the profiles of drug susceptibilities of M. tuberculosis and MAC organisms replicating within the type II pneumocytes. These findings are useful to precisely assess or predict the in vivo therapeutic activity of a given antimycobacterial drug from its in vitro activity. In this article, I have thoroughly reviewed the status of the development of new antimycobacterial drugs. There are a number of difficulties in the drug-design for the development of new drug formulations with increased potential for antimycobacterial effects, excellent pharmacokinetics, and tolerability. It should be emphasized that the most urgent goal of chemotherapy of tuberculosis and MAC infections, especially that associated with HIV infection, is to develop highly active, low-cost drugs which can be used not only in industrialized countries but also in developing countries, since the incidences of AIDS-associated intractable tuberculosis is rapidly increasing in the latter.
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PMID:[Prospects for development of new antituberculous drugs]. 1223 50

We have characterized envelope protein pseudotyped HIV-2 particles derived from two HIV-2 isolates termed prCBL23 and CBL23 in order to define the role of the envelope protein for the Lv2-mediated restriction to infection. Previously, it has been described that the primary isolate prCBL23 is restricted to infection of several human cell types, whereas the T cell line adapted isolate CBL23 is not restricted in these cell types. Molecular cloning of the two isolates revealed that the env and the gag gene are responsible for the observed phenotype and that this restriction is mediated by Lv2, which is distinct from Ref1/Lv1 (Schmitz, C., Marchant, D., Neil, S.J., Aubin, K., Reuter, S., Dittmar, M.T., McKnight, A., Kizhatil, K., Albritton, L.M., 2004. Lv2, a novel postentry restriction, is mediated by both capsid and envelope. J. Virol. 78 (4), 2006-2016). We generated pseudotyped viruses consisting of HIV-2 (ROD-ADeltaenv-GFP, ROD-ADeltaenv-RFP, or ROD-ADeltaenv-REN) and the prCBL23 or CBL23 envelope proteins as well as chimeric proteins between these envelopes. We demonstrate that a single amino acid exchange at position 74 in the surface unit of CBL23-Env confers restriction to infection. This single point mutation causes tighter CD4 binding, resulting in a less efficient fusion into the cytosol of the restricted cell line. Prevention of endosome formation and prevention of endosome acidification enhance infectivity of the restricted particles for GHOST/X4 cells indicating a degradative lysosomal pathway as a cause for the reduced cytosolic entry. The described restriction to infection of the primary isolate prCBL23 is therefore largely caused by an entry defect. A remaining restriction to infection (19-fold) is preserved when endosomal acidification is prevented. This restriction to infection is also dependent on the presence of the point mutation at position 74 (G74E).
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PMID:Role of HIV-2 envelope in Lv2-mediated restriction. 1566 Nov 66

Antiretroviral chemotherapy penetrates the CNS poorly. CNS HIV, thus sheltered, may injure the brain and complicate control of systemic HIV infection. Microglial cells play a major role in HIV persistence in the CNS but are rarely targeted for gene delivery. Because recombinant SV40 vectors (rSV40s) transduce other phagocytic cells efficiently, we tested rSV40 delivery of anti-HIV genetic therapy to microglial cells. Microglia prepared as enriched cultures from human fetal brain, were transduced with marker vectors, SV(RFP) and SV(Nef/FLAG), respectively, carrying DsRed and HIV-1 Nef bearing a FLAG epitope. By immunostaining and FACS, 95% of unselected cells expressed the transgenes, without detectable toxicity. Microglia were transduced with SV(AT), carrying human alpha1-antitrypsin (alpha1AT), which blocks Env and Gag processing. SV(AT)-treated microglia strongly resisted challenge with HIV-1BaL, even when microglia were transduced with SV(AT) following HIV challenge. Thus, rSV40s effectively transduce microglia and protect them from HIV.
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PMID:Using gene delivery to protect HIV-susceptible CNS cells: inhibiting HIV replication in microglia. 1641 41

The non-tuberculous mycobacteriosis (NTM) is not a unitary disease. It is a general term for the bronchopulmonary diseases caused by any mycobacterium other than M. tuberculosis. We don't call the pulmonary "pseudomoniosis" for the diffuse bronchiectasis caused by Pseudomonas aeruginosa, though conditions of the disease looks like NTM. The name of NTM represents that the causativebacteria belong to the same species with M. tuberculosis which causes serious pulmonary infectious disease. The pulmonary diseases caused by M. kansasii or M. szulgai are usually treated by RFP, EB and INH, the same regimens with tuberculosis, which generally lead to sufficient results for patients. But for MAC diseases, the number of patients is top of NTM in Japan, recent treatment with new-macrolides and some anti-tuberculous drugs generally does not bring about the desired effect. The plenty clinical experiences for NTM in HIV positive patients have lead to such new regemens in the USA. For NTM caused by rare Mycobacterium detectedvery seldom, clinical experiences and knowledge are definitely insufficient. (1) Present state of therapy for pulmonary MAC disease (drug therapy): Yoshihiro KOBASHI (Division of Respiratory Diseases, Department of Medicine, Kawasaki Medical School, Kurashiki, Okayama Prefecture) Co-operative study of Research Committee of Mycobacterium in the Chugoku and Shikoku areas revealed that the combined therapy according to the guidline is clinically appropriate for pulmonary Mycobacterium avium complex (MAC) disease. (2) Relapse and chemotherapy duration of pulmonary Mycobacterium avium complex infection: Atsuyuki KURASHIMA (Division of Clinical Research, National Organization Tokyo National Hospital, Kiyose, Tokyo) Reviewing the 71 relapses out of 1170 pulmonary MAC infection cases, he indicated that 11.3% relapsed during the chemotherapy continuation, 23.9% after the reduction of chemotherapy, 64.8% after the termination of chemotherapy. In the last group, there is no correlation to the relapse period after the end of treatment with the preceding chemotherapy duration. It is supposed that the main cause of these relapses are enviromental re-infection. (3) Chemotherapy for pulmonary M. kansasii disease: Katsuhiro SUZUKI (Clinical Research Center, Nationl Organization Kinki-chuo Chest Medical Center, Sakai, Osaka) Analysis of 938 pulmonary mycobacteriosis in 2003 revealed that 244 (26%) patients suffered from NTM, in which 66 (27% of NTM) were M. kansasii disease. The 48 (73%) patients were male. From 2001 to 2004, in the 190 M. kansasii patients treated by anti-tuberculous drugs, H/R/E prescribed for 84 cases (44%), other 41% of prescriptions included CAM and (or) LVFX. Almost all patients were converted into bacilli negative in about 30 days with any prescription. (4) Treatment and management for NTM patients in aprivate clinic: Seiji MIZUTANI (Mizutani Respiratory Clinic, Nerima ward, Tokyo) Analysing clinical experiences, he emphasized that most NTM patients with some symptoms visits private clinics in the first place. In Japan, diagnosis of NTM with radiological and bacteriological examinations is not difficult, and most NTM patients can be controlled as the outpatients of the clinics. (5) Surgical Treatment for non-tuberculous mycobacteriosis: Kouji KIKUCHI (Division of Chest Surgery, Medical Center, Saitama Medical School, Iruma county, Saitama Prefecture) The 9 NTM cases surgically treated were analysed, 8 were MAC cases and 1 was M. kansasii case. The main reasons for sugical resection were, continuous hemoptisis, continuous productive cough, or exacerbation on chest X-ray features. The NTM bacilli were positive in 8 cases, another one was bacilli negative, though X-ray shadows increased. After the surgery, expectoration of bacilli converted to negative in 5 SPECIAL COMMENTARIES: Can pneumonectomy be an acceptable procedure for non-tuberculous mycobacterial infection?: Yuji SHIRAISHI (Division of Chest Surgery, Fukujuji Hospital, Kiyose, Tokyo) The 11 NTM patients were analysed, who underewent pneumonectomy. The median blood loss was 555 ml and there was no operative mortality. Bronchpleural fistula or empyema occured in 4 patients. The bacilli negative conditions were achieved in all patients after surgery. The NTM is not a legal epidemic disease and Japanese Tuberculosis Prevention Act doesn't cover this disease. The medical treatment insurance system doesn't contain the NTM in the list of applicable diseases in Japan. Though these some problems with increasing numbers of patients remain in clinical practice, chairpersons hope that this symposium will be a milestone for the generalized progress of treatment and management of NTM in Japan.
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PMID:[Treatment of non-tuberculous pulmonary mycobacteriosis]. 1647 99

HIV and tuberculosis (TB) are leading global causes of mortality and morbidity, and yet effective treatment exists for both conditions. Rifamycin-based antituberculosis therapy can cure HIV-related TB and, where available, the introduction of highly active antiretroviral therapy (HAART) has markedly reduced the incidence of AIDS and death. Optimal treatment regimens for HIV/TB co-infection are not yet clearly defined. Combinations are limited by alterations in the activity of the hepatic cytochrome P450 (CYP) enzyme system, which in particular may produce subtherapeutic plasma concentrations of antiretroviral drugs. For example, protease inhibitors often must be avoided if the potent CYP inducer rifampicin is co-administered. However, an alternative rifamycin, rifabutin, which has similar efficacy to rifampicin, can be used with appropriate dose reduction. Available clinical data suggest that, for the majority of individuals, rifampicin-based regimens can be successfully combined with the non-nucleoside reverse transcriptase inhibitors nevirapine and efavirenz. Most available HAART regimens in areas that have a high burden of TB contain one or the other of these drugs as a backbone. However, significant questions remain as to the optimal dose of either agent required to ensure therapeutic plasma concentrations, especially in relation to particular ethnic groups. The timing of HAART initiation after starting antituberculosis therapy continues to be controversial. Debate centres upon whether early initiation of HAART increases the risk of paradoxical reactions (immune reconstitution-related events) and other adverse events, or whether delay greatly elevates the risk of disease progression. Further prospective clinical data are needed to help inform practice in this area.
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PMID:Tuberculosis and HIV co-infection: a practical therapeutic approach. 1718 73


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