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

Cytomegalovirus (CMV) infection is one of the most important opportunistic infections in AIDS. The most common manifestation of neurological CMV disease in HIV infection is retinitis followed by encephalitis, polyradiculopathy, and multifocal neuropathy. Untreated necrotizing retinitis proceeds to blindness but can readily be diagnosed by ophthalmological examination. CMV polyradiculopathy presents as subacute leg weakness, paraesthesia, and urinary retention. Untreated patients develop ascending paralysis and die within weeks. Multifocal neuropathy commonly affects the radial, ulnar, and peroneal nerves but cranial nerves may also be involved. Confusion, cranial nerve palsies, and hyperreflexia are signs of ventriculoencephalitis, whereas the presentation of diffuse micronodular encephalitis is often asymptomatic. The diagnostic approach relies on the detection of CMV DNA in the cerebrospinal fluid for polyradiculopathy, encephalitis, and neuropathy. Neuroimaging can exclude other causes of encephalitis and polyradiculopathy. Ganciclovir, foscarnet, and cidofovir monotherapy are current medical treatment options. Intraocular administration can be used for refractory retinitis, but additional systemic prophylaxis is required to suppress extraocular disease. Ganciclovir and foscarnet have improved the prognosis of multifocal neuropathy and polyradiculopathy, but response rates for encephalitis are low. However, despite therapy survival of central nervous CMV disease is still limited to months. Recently highly active antiretroviral therapy (HAART) has decreased the overall incidence of CMV disease in AIDS. Furthermore (HAART) has become a mainstay for CMV therapy by improving the patient's immunocompetence against CMV.
Int J STD AIDS 1999 Mar
PMID:Neurological manifestations of cytomegalovirus infection in the acquired immunodeficiency syndrome. 1034 Jan 95

Varicella zoster virus (VZV) is an uncommon but well recognized cause of neurological disease in HIV-infected patients. Analysis of cerebrospinal fluid (CSF) using the polymerase chain reaction (PCR) in HIV-infected patients presenting with neurological disease has increasingly allowed diagnosis of VZV-associated pathology. We report clinical, radiological and virological data from 15 consecutive patients with VZV-associated neurological disease. Clinical presentation was varied, including meningo-encephalitis in 9 and isolated cranial nerve palsies in 6. VZV deoxyribonucleic acid (DNA) was detected by PCR in CSF of 11/15; pleocytosis was present in only 6/15, raised protein in 11/15. Magnetic resonance imaging (MRI) appearances were focal signal abnormalities in 8, meningeal enhancement in 2 and normal in 2. With specific anti-VZV therapy 10 patients recovered fully. The predictive value of PCR on CSF for diagnosis of VZV-associated neurological disease should take into account the patient's clinical presentation, concurrent infections and response to anti-VZV therapy.
Int J STD AIDS 2001 Feb
PMID:Varicella zoster virus-associated neurological disease in HIV-infected patients. 1123 8

Although influenza vaccination is recommended for individuals with HIV infection, there are no data indicating an increased incidence or severity of influenza in this population. We sought to describe the clinical manifestations and morbidity of influenza in HIV-infected patients. All cases of influenza occurring in HIV-infected individuals over 3 years at a large county hospital were reviewed. Forty-three cases of influenza were diagnosed. Most patients presented with typical signs and symptoms of influenza, including cough (90%), myalgias (64%), and fever (52%). Sore throat and headache occurred in less than half of patients. The mean CD4 cell count and HIV viral load in patients with influenza was 340 cells/mm(3) and 3.34 log copies/ml, respectively. No significant differences in CD4 counts or viral loads were noted in patients with pneumonia (n=7) compared with patients without pneumonia (n=36), P>0.5. Six patients were hospitalized. One patient each had encephalitis and renal failure, although the relationship to influenza was not clear. No new or unusual clinical manifestations were observed. The rate of pulmonary complications was similar to other studies in HIV-negative patients; however, the hospitalization rate was higher than commonly seen in HIV-negative individuals.
Int J STD AIDS 2001 Oct
PMID:Clinical manifestations of influenza in HIV-infected individuals. 1156 31

The aim of the study was to provide more comprehensive data on the clinical characteristics of hospitalized AIDS patients in Cambodia. Chart review of 381 HIV-infected patients admitted to a public hospital in Phnom Penh, Cambodia between December 1999 and May 2000 was performed. The in-hospital mortality rate was 43.6%. Approximately 50% of patients had two or more concurrent illnesses. Very advanced HIV disease was common, with CD4 cell counts below 10 cells/mm(3) in 43.2%. Only 28.3% of the patients had documentation of their HIV infection prior to hospitalization. Chronic diarrhoea was the most frequent opportunistic illness (41.2%), followed by tuberculosis (26%), cryptococcal meningitis (12.6%), Pneumocystis carinii pneumonia (8.4%), and encephalitis (4.7%). Chronic diarrhoea and tuberculosis were the most important opportunistic infections observed in HIV-infected hospitalized patients in Cambodia. These findings illustrate the need for early diagnosis of HIV-infection, effective prophylaxis for opportunistic infections and improved access to antiretroviral therapy in Cambodia.
Int J STD AIDS 2003 Jun
PMID:Spectrum of opportunistic infections in hospitalized HIV-infected patients in Phnom Penh, Cambodia. 1281 70

We assessed the seroprevalence of Toxoplasma gondii infection and incidence of toxoplasma encephalitis (TE) in 844 non-haemophiliac HIV-infected patients in Taiwan between June 1994 and April 2003. Approximately 70% (69.3%) of them had a baseline CD4+ lymphocyte count of 200 x 10(6)/L or less, and more than 70% (73.9%) having initiated highly active antiretroviral therapy. The seroprevalence of T. gondii infection was 10.2%, which did not differ with sex,age,route of transmission, birth inside or outside of Taiwan, or CD4+ lymphocyte stratifications. After a median observation duration of 603 days (range, 1-3264 days), 10 (1.2%) patients developed 11 episodes of TE after a median interval of 30 days (range, 1-941 days) between enrolment and diagnosis of TE, with an incidence of 0.59 per 100 person-years (PY) (95% confidence interval, 0.56-0.63 per 100 PY). We concluded that the incidence of TE of HIV-infected patients in Taiwan was lower than that reported in western countries because of a lower seroprevalence of T. gondii infection and use of antimicrobial prophylaxis and antiretroviral therapy, although most of the patients were at the late stage of HIV infection.
Int J STD AIDS 2005 Apr
PMID:Prevalence of Toxoplasma gondii infection and incidence of toxoplasma encephalitis in non-haemophiliac HIV-1-infected adults in Taiwan. 1589 84

Type I interferons (IFN-alpha/beta and related molecules) are essential for protective immunity to experimental infection by numerous viruses in the mouse model. In recent years, human primary immunodeficiencies affecting either the production of (UNC-93B deficiency) or the response to (STAT1 and TYK2 deficiencies) these IFNs have been reported. Affected patients are highly susceptible to certain viruses. Patients with STAT1 or TYK2 deficiency are susceptible to multiple viruses, including herpes simplex virus-1 (HSV-1), whereas UNC-93B-deficient patients present isolated HSV-1 encephalitis. However, these immunological defects are not limited to type I IFN-mediated immunity. Impaired type II IFN (IFN-gamma)-mediated immunity plays no more than a minor role in the pathogenesis of viral diseases in these patients, but the contribution of impaired type III IFN (IFN-lambda)-mediated immunity remains to be determined. These novel inherited disorders strongly suggest that type I IFN-mediated immunity is essential for protection against natural infections caused by several viruses in humans.
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PMID:Human primary immunodeficiencies of type I interferons. 1756 26

The objective of the pre-travel consultation is to evaluate the risks associated to travelling and to inform the traveler about their nature and severity and how to prevent them. The evaluation of the risks takes into account the visited country, the type of travel and the characteristics of the traveler. The prevention of feco-oral transmitted diseases, namely traveler's diarrhea, relies primarily on the respect of standards of food and beverage hygiene. Information should be given about other general risks (road accidents, STD's and HIV...). This consultation is the opportunity to update the routine immunizations for adults and children, and to give advice about required (yellow fever vaccine for subsaharan Africa and the amazonian region, tetravalent meningococcal vaccine for the pilgrimage el Hadj) and recommended vaccinations (hepatitis A for all travels with low sanitary conditions; according to destinations: typhoid fever, tick-borne encephalitis, japanese encephalitis, rabies...). Malaria prophylaxis includes preventive measures against mosquito-bites at night and chemoprophylaxis adapted to chloroquine resistance level in the country of destination. In any case, a patient with fever occurring within 2 months after returning from an endemic region needs to take a medical advice because of the potential risk of malaria.
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PMID:[Assessment of travel-associated risks and advice to travelers]. 1763

Toxoplasma seroprevalence was determined in 307 consecutive HIV-infected medical inpatients at the Helen Joseph Hospital, Johannesburg, South Africa, using an enzyme linked immunosorbent assay to detect immunoglobulin G (IgG) and IgM antibodies. The mean age of patients was 36 years, with a female to male ratio of 1.3 to 1. The mean CD4 count was 109 cells/mL. Toxoplasma antibodies were detected in 25 patients (8%). Twenty-two of these patients were IgG positive and IgM negative, i.e. reactivation toxoplasmosis. Only two patients (0.65%) had clinical manifestations of toxoplasmosis (one toxoplasma encephalitis and one retinitis). The risk for toxoplasma encephalitis (TE) was 0.33%. These results indicate that the toxoplasma seroprevalence and the TE risk in this population is low. The implication from this study is that in HIV-infected populations where the toxoplasma seroprevalence is low, the TE risk will be low and empiric treatment of focal brain lesions with anti-toxoplasma therapy may be inappropriate.
Int J STD AIDS 2007 Aug
PMID:Reduced risk of toxoplasma encephalitis in HIV-infected patients--a prospective study from Gauteng, South Africa. 1768 19

West Nile virus (WNV) is a human pathogen that can cause symptomatic infections associated with meningitis and encephalitis. Previously, we demonstrated that replication of WNV inhibits the interferon (IFN) signal transduction pathway by preventing the accumulation of phosphorylated Janus kinase 1 (JAK1) and tyrosine kinase 2 (Tyk2) (J. T. Guo et al., J. Virol. 79:1343-1350, 2005). Through a genetic analysis, we have now identified a determinant on the nonstructural protein 4B (NS4B) that controls IFN resistance in HeLa cells expressing subgenomic WNV replicons lacking the structural genes. However, in the context of infectious genomes, the same determinant did not influence IFN signaling. Thus, our results indicate that NS4B may be sufficient to inhibit the IFN response in replicon cells and suggest a role for structural genes, or as yet unknown interactions, in the inhibition of the IFN signaling pathway during WNV infections.
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PMID:Differential effects of mutations in NS4B on West Nile virus replication and inhibition of interferon signaling. 1771 29

Human primary immunodeficiencies impairing myeloid and/or lymphoid cellular responses to activating receptors other than antigen receptors have recently been described in children with various infectious diseases. Germline mutations in NEMO and IKBA impair NF-kappaB-mediated signalling, at least in response to the stimulation of TLRs, IL-1Rs and TNFRs, and confer a broad predisposition to infections. Mutations in IRAK4 selectively impair TLRs other than TLR3 and most IL-1R responses, and confer a predisposition to pyogenic bacterial diseases, including invasive pneumococcal disease in particular. Mutations in TLR3 and UNC93B1 impair TLR3 responses and confer a predisposition to herpes simplex encephalitis. Mutations in STAT1 impair IFN-gamma and/or IFN-alpha/beta responses and predispose subjects to mycobacterial and viral diseases, respectively. Mutations in IFNGR1 and IFNGR2 impair IFN-gamma responses and confer a predisposition to mycobacterial diseases. Mutations in IL12B and IL12RB1 impair IL-12 and IL-23 responses and predispose subjects to infections caused by mycobacteria and Salmonella. Finally, mutations in TYK2 and STAT3 mostly impair IL-6R responses, conferring a predisposition to staphylococcal disease in particular. The infectious phenotypes associated with these novel leukocyte activation deficiencies are therefore collectively diverse, tightly dependent on the morbid gene and affected pathway, and individually narrow, often restricted to one or a few infectious diseases.
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PMID:Novel primary immunodeficiencies revealed by the investigation of paediatric infectious diseases. 1808 7


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