Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hospital management of 108 HIV/AIDS patients cared for by the genitourinary medicine department, Sheffield, UK between 1984-93 was retrospectively studied to quantify the services utilized by these patients and to detail the management costs (1993 price) of outpatient (OP) services, inpatient (IP) care, investigational services and therapeutic provisions. The services utilized and cost are presented separately for the different clinical stages of the infection and as per patient year. Of the 108 patients, 95 (88%) were males and 13 (12%) females; most males (76.8%) acquired the infection through homosexual exposure, while 46% of females acquired it heterosexually. The mean number of OP consultation per asymptomatic, symptomatic non-AIDS and AIDS patient years were 11.6, 16.4 and 32.8 respectively; the mean number of IP episodes for each of these clinical groups were 0.15, 0.83 and 3.88 with IP stays 0.7, 3.5 and 40.6 days per patient year respectively. The annual costs of OP care (45.26 pounds per consultation), drugs and investigations were, respectively 525 pounds, 213 pounds and 153 pounds per asymptomatic patient year, 742 pounds, 2097 pounds and 224 pounds per symptomatic non-AIDS patient year and 1485 pounds, 2928 pounds and 382 pounds per AIDS patient year. The average annual OP drug cost per patient year showed little change since 1988. However, in the AIDS group, contributions from differing drug classes showed significant changes; while the contribution of antiretroviral drugs fell from 80.2% of the drug cost per AIDS patient year in 1990 to 31.3% in 1993, that from antibiotics rose from 0.3% in 1990 to 26.4% in 1993 and other antivirals from 9.4% in 1988 to 22.6% in 1993. These changes were related to lower recommended daily dosage of zidovudine and to wider prescription of antibiotics for atypical mycobacterial infections and domiciliary gancyclovir for CMV infection. The costs of annual mean IP care, IP drugs, IP investigations and IP procedures per AIDS patient year were 5926 pounds (146 pounds per IP stay), 2983 pounds, 282 pounds and 145 pounds respectively. The overall management cost of one AIDS patient year was 14,131 pounds and lifetime AIDS management cost, based on a mean survival of 17 months, a little more than 20,000 pounds. The annual management cost of an asymptomatic and symptomatic non-AIDS patient year is approximately 1/14th and 1/4th of the cost of an AIDS patient year.
Int J STD AIDS
PMID:Hospital service utilization by HIV/AIDS patients and their management cost in a provincial genitourinary medicine department. 854 14

The eukaryotic 20S proteasome is known to associate with the IFN gamma-inducible regulator PA28. We analyzed the kinetics of product generation by 20S proteasomes with and without PA28. In the absence of PA28, the 20S proteasome rapidly generates peptides that have been cleaved only once, while internal fragments accumulate only slowly. In the presence of PA28, products generated by two flanking cleavages appear immediately as main products while the generation of single-cleavage products is strongly reduced. Kinetic data support a PA28-induced, coordinated double-cleavage mechanism. In particular, degradation of peptides derived from mouse cytomegalovirus pp89 and JAK1 kinase in the presence of PA28 leads to strongly enhanced production of the respective major histocompatibility complex ligands and potential precursors. These results show that PA28 profoundly alters the cleavage mechanism of the proteasome and appears to optimize the generation of dominant T-cell epitopes.
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PMID:Coordinated dual cleavages induced by the proteasome regulator PA28 lead to dominant MHC ligands. 870 30

In order to describe the clinical features of AIDS, particularly injection drug use (IDU) related AIDS in patients attending the Regional Infectious Diseases Unit in Edinburgh a prospective review of the 680 HIV-positive patients, 30% of whom were women and 68% were infected via IDU was undertaken. The commonest AIDS-related clinical problem in Edinburgh was Pneumocystis carinii pneumonia (PCP). Whilst gender differences were not apparent in terms of clinical problems, differences were observed in risk groups as previously reported; Kaposi's sarcoma (KS), cytomegalovirus (CMV) and toxoplasmosis were commoner in homo/ bisexuals whilst oesophageal candidiasis was commoner in drug users. Extrapulmonary tuberculosis was uncommon unlike cohorts from the USA or Italy. Each patient with AIDS can expect 1-2 AIDS-related clinical events per year of survival. Considerable differences in mortality rates by risk group but not by gender were observed and explanations for this difference need to be considered further. The mortality rates for drug users were however remarkably similar to published rates from Amsterdam and the Bronx, New York.
Int J STD AIDS
PMID:Clinical features of AIDS in the Edinburgh City Hospital cohort. 879 81

A study was conducted to examine the inpatient, outpatient and drug therapy costs incurred from initial presentation with HIV infection or AIDS to death, where death occurred between 1990 and 1994. The average lifetime cost per patient was 18,729 pounds being made up of 8428 pounds for inpatient care, 2086 pounds for outpatient care and 8215 pounds for drug therapy. Sixty per cent of patients died at home. Active cytomegalovirus infection was the most common condition encountered in the high cost patients. Escalating drug costs may eventually lead to priority setting for the management of certain opportunistic infections.
Int J STD AIDS
PMID:Lifetime cost of treating a person with HIV infection. 884 5

We examined all reports of adult AIDS cases made to the 2 national surveillance centres in the UK for changes in AIDS defining conditions between January 1982 and September 1994. Differences and changes among persons diagnosed since January 1988 who had and had not been aware of their HIV infection prior to their AIDS diagnosis were of particular interest. Pneumocystis carinii pneumonia (PCP) is the AIDS defining disease most often reported at the initial AIDS diagnosis. Its proportion of all AIDS cases has increased significantly between January 1982 and December 1987 and decreased markedly thereafter. Since January 1988 a significant decrease in the proportion of cases diagnosed with cryptosporidial infection was also observed while increases were observed in the proportion of cases diagnosed with: HIV wasting (chi(1)(2) = 5.56) PML (chi(1)(2) = 19.47), mycobacterium avium complex (chi(1)(2) = 35.76) and pulmonary tuberculosis (chi(1)(2) = 144.0). For cases diagnosed between January 1988 and September 1994, PCP was more likely to be diagnosed in patients previously unaware of their HIV infection (P < 0.01) as was extrapulmonary TB (P < 0.01). In contrast, the following diseases were more likely to be diagnosed in patients already aware of their HIV infection prior to the diagnosis of AIDS: oesophageal candidiasis (P < 0.001), HIV wasting (P = 0.07), mycobacterium avium complex (P = 0.0001), cytomegalovirus disease (P < 0.001), HIV encephalopathy (P = 0.0009) and cryptosporidial infection (P = 0.02). Prophylaxis and anti-retroviral therapy appear to have had a significant impact on the temporal changes of the most frequently diagnosed AIDS diseases. While PCP prophylaxis has substantially reduced the likelihood of a PCP diagnosis at AIDS, the corresponding increase in other opportunistic infections suggests that there may be a need for improved prophylaxis for these conditions.
Int J STD AIDS 1996 Jul
PMID:AIDS defining diseases in the UK: the impact of PCP prophylaxis and twelve years of change. 887 55

A cross-sectional study of a cohort of 49 male human immunodeficiency virus (HIV)-infected intravenous drug users attending the Infectious Diseases Unit of the National University of Malaysia during 1991-94 yielded a clinical profile of these patients. The mean age of respondents was 33.2 years and the mean duration of intravenous drug use was 12.7 years. On average, these men had known of their HIV-positivity for 53.2 weeks. Intravenous drug use was the only reported HIV risk factor in 34 men (69%). Clinical symptoms at intake included fatigue (49%), weight loss (47%), night sweats (31%), fever (14%), and diarrhea (6%), while clinical findings included hepatomegaly (57%), lymphadenopathy (35%), and oral thrush (29%). Anemia (82%), leucocytosis (53%), hypoalbuminemia (43%), hyperglobulinemia (88%), elevated liver enzymes and hyponatremia (57%) were frequent laboratory findings. The prevalences of hepatitis B virus, cytomegalovirus, and toxoplasma infection were 12.1%, 72.7%, and 59%, respectively. A total of 91 diagnoses were made in these 49 patients: most common were pneumonia, tuberculosis, bacteremia, infective endocardiditis, mycotic aneurysm, and psychiatric disorders. The mean duration of known progression to acquired immunodeficiency syndrome (AIDS) in the 7 patients at this stage was 391 days. Pneumocystis carinii pneumonia was the most common AIDS-defining illness. Three months into the study, 19 men (57%) had defaulted, reflecting the difficulties of involving drug addicts in research and intervention projects. Moreover, 16 patients (33%) were first confirmed HIV-positive at presentation to the hospital, suggesting that many drug users' HIV status remains unknown until they develop symptoms requiring hospital care.
Int J STD AIDS 1997 Feb
PMID:A study of Malaysian drug addicts with human immunodeficiency virus infection. 906 11

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that is able to persist for decades in its host. HCMV has evolved protean countermeasures for anti-HCMV cellular immunity that facilitate establishment of persistence. Recently it has been shown that HCMV inhibits interferon gamma (IFN-gamma)-stimulated MHC class II expression, but the mechanism for this effect is unknown. IFN-gamma signal transduction (Jak/Stat pathway) and class II transactivator (CIITA) are required components for IFN-gamma-stimulated MHC class II expression. In this study, we demonstrate that both a clinical isolate and a laboratory strain of HCMV inhibit inducible MHC class II expression at the cell surface and at RNA level in human endothelial cells and fibroblasts. Moreover, reverse transcriptase polymerase chain reaction and Northern blot analyses demonstrate that neither CIITA nor interferon regulatory factor 1 are upregulated in infected cells. Electrophoretic mobility shift assays reveal a defect in IFN-gamma signal transduction, which was shown by immunoprecipitation to be associated with a striking decrease in Janus kinase 1 (Jak1) levels. Proteasome inhibitor studies with carboxybenzyl-leucyl-leucyl-leucine vinyl sulfone suggest an HCMV-associated enhancement of Jak1 protein degradation. This is the first report of a mechanism for the HCMV-mediated disruption of inducible MHC class II expression and a direct virus-associated alteration in Janus kinase levels. These findings are yet another example of the diverse mechanisms by which HCMV avoids immunosurveillance and establishes persistence.
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PMID:Human cytomegalovirus inhibits major histocompatibility complex class II expression by disruption of the Jak/Stat pathway. 948 Sep 77

A novel form of therapy, the intravitreal ganciclovir implant (Vitrasert), was used to treat cytomegalovirus (CMV) retinitis in AIDS, when it was not possible to continue systemic therapy or disease progression was evident despite conventional intravenous treatment. A review of the ophthalmic and general health data, operative records and fundus photographs of 9 individuals who had Vitrasert implantation surgery in Edinburgh. Two patients received bilateral replacement implant procedures. Visual acuity, concomitant anti-CMV therapy, complications of implantation and control of retinitis were documented until final follow-up. Control of CMV retinitis was achieved in all individuals at one month postoperatively and remained controlled for a mean period of 5.8 months. Postoperative complications were mild and transient in all but 2 eyes of 2 patients who developed non-progressive macula oedema. Blinding complications as a result of surgery were not encountered and retinal detachment was not observed in this series. Vitrasert implantation is an acceptable and well tolerated treatment for CMV retinitis when systemic therapy fails to control disease progression.
Int J STD AIDS 1998 Apr
PMID:Intravitreal sustained-release ganciclovir implantation to control cytomegalovirus retinitis in AIDS. 959 51

We aim to assess the usefulness of the cytomegalovirus (CMV) pp65 antigenaemia test, also called the CMV direct antigen test (DAT), in the management of patients with advanced human immunodeficiency virus (HIV) infection; we studied all patients who had pp65 assays between 8 September 1995 and 30 August 1996. Twenty-three patients had 31 tests. The mean CD4 cell count was 20/mm3. The tests were negative in 16 patients, of whom 12 have not developed CMV end-organ disease after a mean follow up of 114 days (range 14-269 days), whilst the remaining 4 patients had previously treated CMV disease. Eleven patients had positive tests: 4 had active CMV disease, 2 subsequently developed CMV retinitis, 2 died within a fortnight of multi-drug resistant tuberculosis (MDR-TB), one was lost to follow up and 2 have remained disease-free. This test has a positive predictive value of 43% and a negative predictive value of 94%, Fisher's exact test P=0.03. The pp65 antigenaemia assay can be performed in a standard virology laboratory avoiding the problems associated with polymerase chain reaction (PCR), a result is available within 5 h, and it is semi-quantifiable. However, a large prospective study is required to determine the comparative value and roles of the pp65 antigenaemia assay and DNA PCR in the management of CMV disease, especially with regard to the use of primary prophylaxis and pre-emptive therapy.
Int J STD AIDS 1998 Sep
PMID:Cytomegalovirus pp65 antigenaemia as an indicator of end-organ disease in AIDS. 976 40

Variation in the clinical stage at which AIDS is diagnosed has hindered the ability of investigators to generate survival estimates which are stable across study cohorts. As a result, little is known about how clinical and sociodemographic factors are associated with survival, independent of AIDS diagnosis stage. By estimating survival following seroconversion while adjusting for baseline CD4 lymphocyte count, the present study generated survival determinants which were unconfounded by time-related changes in AIDS diagnosis. This study's findings indicate that the following factors were associated with significant decreases in HIV-related survival: older age; self-report of no known HIV transmission risk factors; and presence of cytomegalovirus, Mycobacterium avium complex, and Pneumocystis carinii pneumonia. Furthermore, survival decreased in a monotonic fashion with decreases in baseline CD4 count and with increases in calendar period. While this study's findings are consistent with previous investigators' reports of AIDS survival determinants, it will be important for future investigators to refine and update estimates of HIV-related survival determinants as clinical care for HIV-infected patients continues to improve.
Int J STD AIDS 1999 Jan
PMID:Determinants of survival in HIV-positive patients. 1021 25


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