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

The purpose of this study was to assess the sensitivity and specificity of the polymerase chain reaction (PCR) on induced sputum (IS) for the diagnosis of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients, as well as its diagnostic value and cost as a routine clinical tool. Forty-nine patients with suspected PCP who had IS were studied and if negative, followed by bronchoalveolar lavage (BAL). Pneumocystis carinii was detected in these samples using standard staining techniques. Polymerase chain reaction was used with IS samples in a blinded fashion. The patients with negative BAL samples were closely monitored for 1 month. In the absence of any clinical or radiologic features of PCP during this period, they were considered as being free of PCP. The cost analysis considered only the direct costs of the various tests in three diagnostic strategies: routine BAL (BAL); IS with standard staining, if negative, followed by BAL (IS); and IS with standard staining followed, if negative, by PCR on IS samples (PCR-IS). Using standard staining P carinii was found in 13 cases (6 IS and 7 BAL). None of the 36 patients with negative BAL developed further signs of PCP. Thus, the prevalence of PCP was 26.5% and the sensitivity and specificity of BAL were 100%. Standard staining of IS had a specificity of 100% and a sensitivity of 46.5%. The sensitivity and specificity of PCR-IS were each 100%. The costs of strategies BAL, IS, and PCR-IS were $14,010, $18,300, and $18,040, respectively. The costs of the BAL strategy depended only on the cost of the relevant tests, whereas the costs of strategies IS and PCR-IS depended on the costs of the tests, the sensitivity of IS with standard staining, and the prevalence of PCP in the test population. The routine clinical use of PCR-IS is currently limited by the time required to obtain the results.
 ...
PMID:Use of the polymerase chain reaction technique on induced-sputum samples for the diagnosis of Pneumocystis carinii pneumonia in HIV-infected patients. A clinical and cost-analysis study. 761 Nov 87

Bronchoscopy was carried out in 32 HIV seropositive patients, most with AIDS during the period between January 1992 and August 1993. In 14 patients tuberculosis was diagnosed, in 13 it was bacteriologically confirmed. The mean age of the examined patients was 35.5 years (range 22-49 years). In 50% of the BAL samples bacterioscopy was positive. Bacteriological examination of the sputum and BAL fluid (bacterioscopy and culture) produced a confirmation of tuberculosis in 99.9% of the cases.
 ...
PMID:[The role of bronchoscopy and bronchoalveolar lavage in diagnosis of pulmonary tuberculosis in AIDS]. 763 65

Tat is a potent trans-activating protein encoded by the HIV genome. It is essential for viral replication, but has pleiotropic effects on host cells as well. We demonstrated that exogenous recombinant Tat increases immunoglobulin (Ig) and interleukin 6 (IL-6) production in vitro by normal uninfected peripheral blood mononuclear cells by 100-500%. The optimal Tat concentration was 100 ng/ml, but even a low concentration of 1 ng/ml induced a response in most subjects. The observed induction was inhibited by monoclonal anti-Tat antibodies and 2,3-dimercapto-1-propanol. Both anti-IL-6 antibodies and IL-6 antisense oligonucleotides inhibited Tat-induced IgG and IgA synthesis to some degree, whereas induction of IgM appeared to be independent of IL-6. We conclude that Tat can function in vitro in the absence of any other viral structures and induce Ig and IL-6 production; the clinical significance of these findings remains as yet undetermined.
 ...
PMID:HIV type 1 Tat protein induces immunoglobulin and interleukin 6 synthesis by uninfected peripheral blood mononuclear cells. 798 83

With the increased number of HIV infected patients, tuberculosis has become more frequent in Europe, USA and particularly in Africa. Impaired immunity, poor life conditions and high prevalence of tuberculosis in the general population facilitate the transmission of the disease. Tuberculosis is often seen early in the course of HIV infection and sometimes reveals the underlying immunodeficiency. Most of these cases are due to reactivation of earlier primo-infection when tuberculosis occurs later in the HIV disease, it may be secondary to a recent contagion. The infection may be localized in the lungs or in extrathoracic sites such as lymph nodes, liver, spleen, blood or meninges. The diagnosis is based on direct visualization of acid fast bacilli in gastric aspirate or BAL, on positive blood cultures or in histological findings which often show atypical granulomatous reaction without marked caseation. The role of the intracutaneous tuberculin test remain questionable as it often proves negative. A positive skin reaction can be useful for the diagnosis of tuberculosis, however, this is rarely observed. An early diagnosis is important in order to improve the prognosis and this justifies the frequent instauration of empiric treatment. The usual quadritherapy is efficacious and when started early permits in most cases a favorable outcome. The duration of treatment is poorly standardized but approaches 9-12 months in most instances. The drugs are not always well tolerated. A life-long maintenance therapy seems to have become necessary and primary prophylaxis might be of interest. The increased occurrence of drug resistant stains adds to the interest of preventing transmission, particularly in the hospital.
 ...
PMID:[Tuberculosis and HIV]. 819 Oct 74

Recent studies have suggested that failure of pentamidine prophylaxis against Pneumocystis carinii pneumonia (PCP) may be due to reduced deposition of pentamidine in the upper lobes. In this study, we performed bronchoalveolar lavage from the apical segment of the upper lobe and the middle lobe in 51 HIV-positive patients, all of whom were receiving prophylaxis with aerosolized pentamidine, who had presented with acute respiratory symptoms. Lavage fluid from each lobe was assayed for pentamidine using high-performance liquid chromatography (HPLC). The number of clusters of P carinii were counted after staining with a Wright-Giemsa stain. The patients were subclassified as PCP-positive (32 patients) and PCP-negative (19 patients) on the basis of the presence/absence of P carinii clusters in their BAL fluid. The concentration of pentamidine in the upper lobe compared with the middle lobe was no different (using paired Student's t tests) for either PCP-positive patients or PCP-negative patients. In comparing the positive with the negative subjects, using unpaired Student's t test, there was no difference in the concentration of pentamidine in the upper lobe or the middle lobe. For PCP-positive patients, the numbers of P carinii clusters were on average higher in the upper lobes (mean +/- SD: upper = 14.9 +/- 16.6, middle 7.5 +/- 10.8, p = 0.013, paired Student's t test), but there was no correlation between lobar P carinii cluster counts and pentamidine levels. We conclude that the absence of a relationship between cluster count and pentamidine level, the similarity in regional pentamidine levels between upper and middle lobes, as well as the similarity in pentamidine levels between the PCP-positive and PCP-negative groups indicate that the regional dose of pentamidine is not the determining factor as to whether aerosolized pentamidine prophylaxis will succeed or fail.
 ...
PMID:Lobar pentamidine levels and Pneumocystis carinii pneumonia following aerosolized pentamidine. 827 83

Pneumocystis carinii pneumonia (PCP) in HIV-infected patients remains a life-threatening complication in the course of HIV infection. Despite effective treatment, mortality may still be as high as 10%. The identification of risk factors associated with a lethal outcome might be helpful as a guide to therapy for patients at risk and in the evaluation of new drugs with anti-pneumocystic activity. In a retrospective study 58 first episodes of HIV-associated PCP without prophylaxis were analyzed. Variables associated univariately with higher mortality were identified. A prognostic rule was established in a multivariate approach using canonical discriminant analysis. Cut-off values for parameters included were determined in order to allow a clinically applicable estimate of the individual risk. Variables associated with early mortality were hemoglobin, hematocrit, platelet count, albumin, total protein, gamma-globulins, and AaDO2. LDH values, percentage of neutrophils in the BAL, as well as the cellular immunologic state as indicated by CD4-cell count were not significantly associated with the outcome. The discriminant function yielded the best classification results with the inclusion of hemoglobin, albumin, and gamma-globulins (overall accuracy 86%). Two or more of the following parameters were associated with a 14-fold increased risk of in-hospital mortality: hemoglobin less than 10 g/dl, albumin less than 3 g/dl, and gamma-globulins less than 1.2 g/dl. This prognostic rule was 80% sensitive and 94% specific with a negative predictive value of 94%, yielding an overall accuracy of 91%. Patients with HIV-associated PCP with a positive prognostic rule have a 14-fold increased risk for in-hospital lethal outcome. This discriminant rule may be helpful in identifying patients at risk.
 ...
PMID:Predicting in-hospital outcome in HIV-associated Pneumocystis carinii pneumonia. 855 84

The clinical benefit of the human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) is limited by the rapid selection of inhibitor-resistant viral variants. However, it may be possible to enhance the clinical utility of this inhibitor class by deriving compounds that express both high levels of antiviral activity and an augmented pharmacokinetic profile. Accordingly, we developed a new class of NNRTIs, the 1, 4-dihydro-2H-3, 1-benzoxazin-2-ones. L-743, 726 (DMP-266), a member of this class, was chosen for clinical evaluation because of its in vitro properties. The compound was a potent inhibitor of the wild-type HIV-1 RT (Ki = 2.93 nM) and exhibited a 95% inhibitory concentration of 1.5 nM for the inhibition of HIV-1 replicative spread in cell culture. In addition, L-7743, 7726 was found to be capable of inhibiting, with 95% inhibitory concentrations of < or = 1.5 microM, a panel of NNRTI-resistant mutant viruses, each of which expressed a single RT amino acid substitution. Derivation of virus with notably reduced susceptibility to the inhibitor required prolonged cell culture selection and was mediated by a combination of at least two RT amino acid substitutions. Studies of L-743, 726 in rats, monkeys, and a chimpanzee demonstrated the compound's potential for good oral bioavailability and pharmacokinetics in humans.
 ...
PMID:L-743, 726 (DMP-266): a novel, highly potent nonnucleoside inhibitor of the human immunodeficiency virus type 1 reverse transcriptase. 859 86

We have approached the development of a human immunodeficiency virus type 1 (HIV-1) therapeutic product by producing immune cells stably resistant to HIV-1. Promonocytic CD4+ cells (U937) were made resistant to HIV-1 by the introduction of a DNA construct (pNDU1A,B,C) that contained three independent antisense sequences directed against two functional regions, transactivation response and tat/rev, of the HIV-1 target. Each sequence was incorporated into the transcribed region of a U1 snRNA gene to generate U1/HIV antisense RNA. Stably transfected cells expressed all three U1/HIV antisense transcripts, and these transcripts accumulated in the nucleus. These cells were subjected to two successive challenges with HIV-1 (BAL strain). The surviving cells showed normal growth characteristics and have retained their CD4+ phenotype. In situ hybridization assays showed that essentially all of the surviving cells produced U1/HIV antisense RNA. No detectable p24 antigen was observed, no syncytium formation was observed, and PCR-amplified HIV gag sequences were not detected. Rechallenge with HIV-1 (IIIB strain) similarly yielded no infection at a relatively high multiplicity of infection. As a further demonstration that the antisense RNA directed against HIV-1 was functioning in these transfected immune cells, Tat-activated expression of chloramphenicol acetyltransferase was shown to be specifically inhibited in cells expressing Tat and transactivation response region antisense sequences.
 ...
PMID:Stable human immunodeficiency virus type 1 (HIV-1) resistance in transformed CD4+ monocytic cells treated with multitargeting HIV-1 antisense sequences incorporated into U1 snRNA. 909 86

The detection of Pneumocystis carinii DNA in serum, a potentially useful and attractive tool for the diagnosis of P. carinii infection and for monitoring the success of therapeutic interventions, remains a controversial issue. In a prospective study of 29 immunocompromised patients, including 16 with HIV infection undergoing bronchoscopy and bronchoalveolar lavage, we examined 32 bronchoalveolar lavage fluids and multiple serum samples for the presence of P. carinii DNA by using mitochondrial rRNA gene fragments pAZ102-E as pAZ102-H as primers. Samples from 7 immunocompetent patients were analysed as a control. 13/32 bronchoalveolar lavage fluids of immunocompromised patients (41%), but none of the controls, had both microscopic evidence of P. carinii cysts as well as P. carinii DNA detection. In none of these patients were serum samples obtained before therapy positive for P. carinii DNA, while in 1 patient (8%), P. carinii DNA was detected in 2/5 serum samples obtained during therapy. Interestingly, PCR detected P. carinii DNA in sera of 3/15 immunocompromised patients without detection of P. carinii DNA or organisms in BAL. Two of these 3 patients were taking secondary prophylactics for P. carinii pneumonia. In conclusion, PCR for P. carinii DNA in serum, at least in certain circumstances, may be of little value for the diagnosis of P. carinii pneumonia.
 ...
PMID:Serum PCR of Pneumocystis carinii DNA in immunocompromised patients. 918 52

This retrospective study reports the results of surgical lung biopsies in 21 patients infected by HIV. Diagnostic was assessed by surgical lung biopsies in 66% of cases with a 5% immediate post-operative mortality and a 80% survival rate after one month. Therapeutic management was modified in 38% of cases. These results are in concordance with previously published literature and emphasize that such a procedure should only be performed after other diagnostic procedures, including at least a bronchial endoscopy associated to a BAL and/or transbronchial biopsies.
 ...
PMID:[Surgical pulmonary biopsies in patients with HIV infection: results apropos of a series of 21 cases]. 918 50


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>