Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pruritus is a common manifestation of dermatologic diseases, including xerotic eczema, atopic dermatitis, and allergic contact dermatitis. Effective treatment of pruritus can prevent scratch-induced complications such as lichen simplex chronicus and impetigo. Patients, particularly elderly adults, with severe pruritus that does not respond to conservative therapy should be evaluated for an underlying systemic disease. Causes of systemic pruritus include uremia, cholestasis, polycythemia vera, Hodgkin's lymphoma, hyperthyroidism, and human immunodeficiency virus (HIV) infection. Skin scraping, biopsy, or culture may be indicated if skin lesions are present. Diagnostic testing is directed by the clinical evaluation and may include a complete blood count and measurement of thyroid-stimulating hormone, serum bilirubin, alkaline phosphatase, serum creatinine, and blood urea nitrogen levels. Chest radiography and testing for HIV infection may be indicated in some patients. Management of nonspecific pruritus is directed mostly at preventing xerosis. Management of disease-specific pruritus has been established for certain systemic conditions, including uremia and cholestasis.
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PMID:Pruritus. 1452 1

Wasting and renal diseases are frequent complications of HIV (human immunodeficiency virus) infection and are associated with accelerated disease progression and increased mortality. Transgenic mice expressing HIV1 under control of the CD4 promoter develop an AIDS-like disease and were used in the present work to study HIV1-induced wasting and kidney pathology. In this study, we reported that disease evolution paralleled increases in serum urea and creatinine levels, indicating an early and progressive deterioration of kidney function; meanwhile the wasting syndrome characterized by up-regulation of the ubiquitine-proteasome pathway and increased level of serum 3-methyl-histidine levels occurred at later stages just prior to death. Further examination of kidney and muscle pathologies revealed a progressive accumulation of CD45(+) cells, first affecting the kidneys. In addition, the onset of disease is accompanied by elevated levels of circulating "regulated on activation, normal and secreted T cell expressed and secreted" (RANTES). These results prompted us to assess the effects of AS602868, a specific small molecule inhibitor of IkappaB kinase 2 (IKK2) on disease progression. Inhibition of the NF-kappaB pathway indeed resulted in increased lifespan, kidney and lean body mass preservation. These beneficial results were associated with a reduction of CD45(+) cells infiltrating the kidneys, amelioration of the renal architecture, and reduced level of circulating RANTES. Together our data provide evidence that IKK2 inhibitors have therapeutic relevance in the treatment of HIV1-associated disorders.
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PMID:IKK2 inhibitor alleviates kidney and wasting diseases in a murine model of human AIDS. 1503 14

Risk factors associated with the occurrence of protease inhibitor (PI)-related severe and serious adverse drug reactions (SADRs) were analyzed in a prospective cohort of 1155 patients who initiated PI-containing therapy. During a total follow-up of 2037 patient-years, 169 SADRs were reported, yielding a rate of 8 incidents per 100 patient-years (95% confidence interval [CI], 6.8-8.6). The most frequent SADRs were elevated transaminase levels (in 49 events); renal colic (27); abnormal hematological findings (23); and metabolic (18), neuromuscular (7), pancreatic (6), cutaneous (6), cardiovascular (5), and psychiatric disorders (5). Among baseline characteristics, plasma human immunodeficiency virus RNA levels of >or=5 log(10) copies/mL (hazard ratio [HR], 1.5; 95% CI, 1.1-2.2), elevated aspartate aminotransferase levels (HR, 1.1 for each 20 IU of elevation; 95% CI, 1.1-1.2), creatinine clearance levels of <70 mL/min (HR, 2.1; 95% CI, 1.2-3.7), test results positive for hepatitis C virus antibodies or hepatitis B surface antigenemia (HR, 2.6; 95% CI, 1.8-3.7), and receipt of indinavir (HR, 1.7; 95% CI, 1.2-2.4) were independently predictive of a SADR. SADRs were frequent in the first 4 months after initiation of highly active antiretroviral therapy but continued to occur after that time period.
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PMID:Incidence of and risk factors for adverse drug reactions in a prospective cohort of HIV-infected adults initiating protease inhibitor-containing therapy. 1530 35

Intravenous administration of immunoglobulin is used for the treatment of many conditions, including primary immunodeficiency states, autoimmune disorders, glomerulonephritides and polyneuropathy. Acute renal failure induced by intravenous immunoglobulin is a known but rare adverse reaction. We have a patient who was treated with IVIG for inflammatory polyneuropathy. Intravenous immunoglobulin therapy 0.5 g/kg/ d was given for 4 days. Three days after completion of IVIG therapy, patient developed decreased urine output. His serum creatinine increased from baseline of 1.3 to 7 mg/dL. Even though IVIG was discontinued, patient required hemodialysis. This case illustrated that IVIG can cause acute oliguric renal failure which is reversible after withdrawal of the drug. Risk factors include pretreatment renal impairment, diabetes mellitus, high concentration of sucrose or glucose in IVIG preparation and older age. Awareness of this serious side effects and recognition of predisposing factors provide means of avoiding a known life threatening complication of IVIG therapy.
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PMID:Acute renal failure resulting from intravenous immunoglobulin therapy. 1554 May 24

Heart failure is a common, progressive, complex clinical syndrome with high morbidity and mortality. Coronary artery disease is its most common cause. The evaluation of symptomatic patients with suspected heart failure is directed at confirming the diagnosis, determining the cause, identifying concomitant illnesses, establishing the severity of heart failure, and guiding therapy. The initial evaluation should include a focused history and physical examination, a chest radiograph, and an electrocardiogram. The presence of heart failure can be confirmed by an echocardiogram. Heart failure is highly unlikely in the absence of dyspnea and an abnormal chest radiograph or electrocardiogram. Radionuclide angiography or contrast cineangiography may be necessary when clinical suspicion for heart failure is high and the echocardiogram is equivocal. Patients with confirmed heart failure should undergo additional testing, including a more detailed history and physical examination; a complete blood count; blood glucose measurement; liver function tests; serum electrolyte, blood urea nitrogen, and creatinine measurements; lipid panel; urinalysis; and thyroid-stimulating hormone level. A serum ferritin level, human immunodeficiency virus test, antinuclear antibody assays, rheumatoid factor test, or metanephrine measurements may be required in selected patients. Patients with coronary artery disease, hypertension, diabetes mellitus, exposure to cardiotoxic drugs, alcohol abuse, or a family history of cardiomyopathy are at high risk for heart failure and may benefit from routine screening.
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PMID:Diagnosis of heart failure in adults. 1560 63

Antiretroviral agents, especially nucleoside reverse transcriptase inhibitors, require significant dosage adjustments in patients who have renal dysfunction and the human immunodeficiency virus (HIV). Some antiretroviral agents and fixed combination preparations are contraindicated in this population. In addition, many preferred antiretroviral regimens may be difficult to administer conveniently in patients with decreased creatinine clearance or in those receiving renal replacement therapies. Some highly active antiretroviral therapy regimens, however, can be used conveniently in patients with HIV and altered renal function.
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PMID:Use of highly active antiretroviral therapy in patients with renal insufficiency. 1589 32

Although various manifestations of pentamidine-induced cardiotoxicity have been reported, to our knowledge, second-degree heart block associated with this agent has not been described. In addition, cardiac adverse effects usually develop after at least 6 days of therapy. We describe a 54-year-old, human immunodeficiency virus-positive man with a history of sulfonamide allergy who received treatment with pentamidine for Pneumocystis jiroveci pneumonia. After only the third dose of pentamidine, it was noted that the patient's heart rate had decreased to 48 beats/minute. Subsequently, five episodes of Wenckebach (Mobitz type 1) heart block with a ventricular rate of 28 beats/minute were observed on continuous cardiac telemetry. Serum electrolyte and creatinine levels remained within normal limits. Within 4 days of discontinuing the pentamidine, the patient's heart rate stabilized at 80 beats/minute without further intervention. Clinicians should be vigilant when monitoring for cardiotoxicity in patients receiving pentamidine throughout the duration of therapy. In addition, they should continue to reserve its use for moderate-to-severe Pneumocystis jiroveci pneumonia for which trimethoprim-sulfamethoxazole is ineffective or contraindicated.
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PMID:Early-onset pentamidine-associated second-degree heart block and sinus bradycardia: case report and review of the literature. 1592 10

The influence of renal function on tenofovir pharmacokinetics was investigated in 193 human immunodeficiency virus (HIV)-infected patients by the use of a population approach performed with the nonlinear mixed effects modeling program NONMEM. Tenofovir pharmacokinetics was well described by a two-compartment open model in which the absorption and the distribution rate constants are equal. Typical population estimates of apparent central distribution volume (V(c)/F), peripheral distribution volume (V(p)/F), intercompartmental clearance (Q/F), and plasma clearance (CL/F) were 297 +/- 28.5 [corrected] liters, 848 +/- 209 [corrected] liters, 80 +/- 15 [corrected] liters/h and 50.5 +/- 3.1 [corrected] liters/h, respectively. Apparent plasma clearance was related to body weight/serum creatinine ratio (BW/S(CR)) and to the existence of a tubular dysfunction. Concomitant treatment with lopinavir/ritonavir was found to decrease tenofovir clearance. Individual Bayesian estimates of CL/F were used to calculate the tenofovir area under the concentration-time curve from time zero to 24 h (AUC(0-24)). In patients without tubular dysfunction, AUC(0-24) values markedly decreased from 6.7 to 1.4 mg . h/liter for BW/S(CR) increasing from 0.44 to 1.73. The relevance of a dosage adjustment based on BW/S(CR) should be further evaluated.
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PMID:Population pharmacokinetics of tenofovir in human immunodeficiency virus-infected patients taking highly active antiretroviral therapy. 1604 48

We compared the results of Tc-99 evaluation of glomerular filtration rate (GFR) vs. the calculation of the creatinine clearance (CCrC) as a predictor for the development of renal insufficiency in pediatric patients following hematopoietic stem cell transplantation (HSCT). We reviewed 95 consecutive patients receiving autologous (n = 37) or allogeneic (n = 58) HSCT at Children's Memorial Hospital between January, 1995 and February, 1998. Diagnoses included leukemia (n = 43), solid tumor (n = 27), bone marrow failure syndrome (n = 12), non-malignant disease (n = 8), CNS tumors (n = 5) and immunodeficiency (n = 3). Tc-99 GFR was compared with a calculated creatinine clearance derived from the Schwartz formula (CCrC) prior to HSCT. These measures of renal function were compared with the patient's subsequent clinical course to determine if patients who developed renal insufficiency of sufficient magnitude as to require continuous veno-venous hemofiltration (CVVH) or dialysis, could have been identified. Overall comparison of the two methods of evaluation of renal function showed low correlation with values obtained by CCrC, which were consistently higher in most patients (r-value 0.01 in the regression analysis and a p = 0.08 95% CI -24.15 to 1.48). When stratified for age, correlation between the two methods was excellent only in children younger than 5 yr of age p = 0.02 95%, CI 0.032-0.49). Eleven patients required therapy with CVVH or dialysis but neither CCrC nor Tc-99 GFR prior to transplant predicted this event. Patients who received TBI were statistically more prone to develop renal insufficiency than those without TBI (p < 0.0001, 95% CI 0.25-0.008). Neither the Tc-99 GFR nor the CCrC was predictive of the development of renal insufficiency in HSCT patients as the majority of patients who required dialysis had normal Tc-99 GFR prior to transplant. The characteristics found in the patients who developed renal insufficiency and required dialysis include: the use of total body irradiation as part of the transplant-conditioning regimen (p < 0.0001) and the use of continuous infusion CSA (p = 0.04).
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PMID:Comparison of Tc-99 measurement of glomerular filtration rate vs. calculated creatinine clearance to assess renal function pretransplant in pediatric patients undergoing hematopoietic stem cell transplantation. 1617 14

Approximately 10% of adult patients with human immunodeficiency virus (HIV) infection have HIV-associated nephropathy (HIVAN). This condition, a leading cause of renal failure, is characterized by damage to specific areas of the renal filtration system. It manifests with increased serum creatinine levels, overt proteinuria, and in some patients, end-stage renal disease (ESRD). The mortality rate for HIVAN-related ESRD is high-30% within the first year of onset. Most instances of HIVAN occur in patients of African descent. Although advances in defining the pathology have been made, the optimal treatment strategy remains unclear. Potential benefits of potent combination antiretroviral therapy, angiotensin-converting enzyme (ACE) inhibitors, and corticosteroids have been reported in small clinical trials and case reports. Cyclosporine is another option, but clinical experience with this agent in managing HIVAN is limited. Few conclusions can be drawn from the limited body of available evidence. Antiretroviral therapy, ACE inhibitors, and corticosteroids are possibly associated with reversal of serum creatinine level increases and proteinuria, but studies are necessary to further define the role of these agents in therapy. Close monitoring is advised when treating any patient with HIVAN.
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PMID:Pharmacotherapy for human immunodeficiency virus-associated nephropathy. 1630 96


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