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)

Suramin sodium is a reverse transcriptase inhibitor with in vitro activity against the human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS). Ninety-eight patients with AIDS manifest as opportunistic infections (n = 38), AIDS with Kaposi's sarcoma (n = 38), AIDS-related complex (n = 20), or AIDS-associated non-Hodgkin's lymphoma (NHL) (n = 2) were treated with suramin sodium at 0.5, 1.0, or 1.5 g/wk for six weeks followed by maintenance therapy with 0.5 or 1.0 g/wk. Of 72 patients who were HIV culture positive before therapy and were assessable for subsequent HIV culture 40% became culture negative during treatment, with no apparent correlation between virus recovery and serum suramin concentration. No immunologic improvement was noted. One complete clinical remission was noted in a patient with Kaposi's sarcoma and stage IV NHL. Seven minor clinical responses were also noted. Toxic reactions were generally reversible, and included fever (78%), rash (48%), malaise (43%), nausea (34%), neurologic symptoms (33%), and vomiting (20%). Suramin-induced neutropenia was noted in 26%, thrombocytopenia in 12%, a serum creatinine level of 180 mumol/L or higher (greater than or equal to 2.1 mg/dL) in 12%, liver dysfunction in 14%, and clinical and/or laboratory evidence of adrenal insufficiency in 23%. Sixteen patients died while receiving suramin or within three weeks of discontinuation of drug therapy due to infection (n = 6), hepatic failure (n = 3), pulmonary Kaposi's sarcoma (n = 2), AIDS encephalitis (n = 2), AIDS-associated NHL (n = 1), iatrogenic hemo-pneumothorax (n = 1), or pulmonary disease of uncertain etiology. Suramin as currently administered cannot be recommended as effective therapy for AIDS.
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PMID:Suramin therapy in AIDS and related disorders. Report of the US Suramin Working Group. 365 Mar 39

To evaluate the immunological state in chronic renal insufficiency, the Authors studied cellular and humoral immunity in 292 patients with chronic renal failure. They were divided into 3 groups: 1) 37 with creatinine clearance between 50 and 20 ml/min; 2) 57 with creatinine clearance between 20 and 8 ml/min; 3) 178 treated by hemodialysis. In vivo and in vitro tests, that is DNCB, PPD skin tests, spontaneous, active and EAC rosettes, surface membrane immunoglobulin test, complement (C3, C4) and serum immunoglobulins were taken as markers of the immune response. Cell-mediated immunity was found to be significantly impaired in patients with terminal renal insufficiency or on hemodialysis and also markedly reduced in patients with non-terminal renal insufficiency. Humoral immunity produced less significant results: the B lymphocyte count and serum immunoglobulins were normal; only C3 levels were found below normal range. Thus it would seem that cell-mediated immunodeficiency appears in an early stage of chronic renal failure and that hemodialysis does not improve this deficiency.
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PMID:The immunological state in chronic renal insufficiency. 698 10

Fluconazole pharmacokinetics, including absolute bioavailability, were determined for one group of controls (n = 10) and two groups of people with human immunodeficiency virus (HIV) infection (those with CD4+ T-cell counts of less than [n = 4] or greater than [n = 9] 200 cells per mm3). Twenty subjects received four doses of fluconazole; three doses were oral (50, 100, and 400 mg), and one dose was intravenous (either 50, 100, or 400 mg). The other three subjects received one or two doses. The groups were comparable in terms of the weight, body mass index, and estimated creatinine clearance of the subjects, but the people with HIV infection were older. Pharmacokinetic parameters indicated linearity in all subjects; the area under the plasma concentration-time curve and the maximum concentration increased in proportion to the dose. The fraction of an oral dose of fluconazole absorbed approximated unity in all three groups of subjects. The mean (+/- standard deviation) plasma clearance of fluconazole was lowest in the group of subjects with low CD4+ T-cell counts; the value for this group was 0.74 +/- 0.19 liter/h, compared with 0.97 +/- 0.19 liter/h in the group with HIV infection and CD4+ T-cell counts of greater than 200 cells/mm3 and 1.18 +/- 0.23 liter/h in the group of control subjects (P < 0.05). The volume of distribution was lower in those with HIV infection (P = 0.04, corrected for weight). The half-life was longest in people with HIV infection and low CD4+ T-cell counts (P = 0.01). This study has shown that some differences do exist between the pharmacokinetics of fluconazole in people with HIV infection and those in noninfected controls.
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PMID:Pharmacokinetics and bioavailability of fluconazole in two groups of males with human immunodeficiency virus (HIV) infection compared with those in a group of males without HIV infection. 748 28

The pharmacokinetics of cidofovir (HPMPC; (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine) were examined at five dose levels in three phase I/II studies in a total of 42 human immunodeficiency virus-infected patients (with or without asymptomatic cytomegalovirus infection). Levels of cidofovir in serum following intravenous infusion were dose proportional over the dose range of 1.0 to 10.0 mg/kg of body weight and declined biexponentially with an overall mean +/- standard deviation terminal half-life of 2.6 +/- 1.2 h (n = 25). Approximately 90% of the intravenous dose was recovered unchanged in the urine in 24 h. The overall mean +/- standard deviation total clearance of the drug from serum (148 +/- 25 ml/h/kg; n = 25) approximated renal clearance (129 +/- 42 ml/h/kg; n = 25), which was significantly higher (P < 0.001) than the baseline creatinine clearance in the same patients (83 +/- 21 ml/h/kg; n = 12). These data indicate that active tubular secretion played a significant role in the clearance of cidofovir. The steady-state volume of distribution of cidofovir was approximately 500 ml/kg, suggesting that the drug was distributed in total body water. Repeated dosing with cidofovir at 3.0 and 10.0 mg/kg/week did not alter the pharmacokinetics of the drug. Concomitant administration of intravenous cidofovir and oral probenecid to hydrated patients had no significant effect on the pharmacokinetics of cidofovir at a 3.0-mg/kg dose. At higher cidofovir doses, probenecid appeared to block tubular secretion of cidofovir and reduce its renal clearance to a level approaching glomerular filtration.
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PMID:Clinical pharmacokinetics of cidofovir in human immunodeficiency virus-infected patients. 757 10

Human immunodeficiency virus associated nephropathy (Hivan) is a distinct renal disease described in patients infected with the human immunodeficiency virus (HIV). Hivan is characterized by a nephrotic syndrome, enlarged kidneys, a histologic finding of focal and segmental glomerulosclerosis, and a very rapid progression to end-stage renal disease (ESRD). No therapeutic intervention has been shown, in a prospective evaluation, to either alter the course of established Hivan or to influence the emergence of Hivan in HIV-infected patients. We conducted a prospective study on 23 consecutively selected patients seen between 1989 and 1992 who were infected with the HIV, 14 (61%) of whom had significant proteinuria (> or = 2+). Percutaneous kidney biopsy was performed in 5 (36%) of the 14 subjects who had significant proteinuria, and histologic examination of the kidney tissue revealed focal and segmental glomerulosclerosis in all 5 cases. Of the 14 subjects with proteinuria, 8 (57%) also had azotemia (serum creatinine level > or = 1.3 mg/dl). Nine (39%) of 23 subjects admitted intravenous drug use, while 9 (39%) of 23 subjects have had an opportunistic infection before enrollment in the study. The known duration of HIV infection before initiation of zidovudine therapy was 10.3 +/- (SD) 8 months. The mean CD4 count before zidovudine therapy was 195.9 +/- 117 (range 21-654) cells/mm3. The mean dose of zidovudine administered was 543 +/- 117 (range 400-800) mg daily for a period of 20.4 +/- 11 (range 6-38) months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Zidovudine is beneficial in human immunodeficiency virus associated nephropathy. 761 46

The efficacy and toxicity of a single versus double gentamicin dose were compared. Fifty-four ill patients with infection susceptible to gentamicin in Department of Internal Medicine, University Hospital Rebro, Zagreb, were included in this study. The following criteria excluded patients from the study: serious renal failure (creatinine > 250 mumol/l), hearing impairment, condition and immunodeficiency. Patients were randomised to receive either gentamicin 4 mg/kg by infusion over a 30 minute period once daily, a single-dose group (SG) (N = 25), or gentamicin 2 mg/kg intravenously twice daily, a double-dose group (DG) (N = 29). Almost all patients in a single-dose group achieved peak therapeutic concentrations, while trough gentamicin concentrations were below the recommended. In a double-dose group, only 70.5% of the patients obtained peak concentrations, and 7.5% of the patients had inadequately high trough gentamicin concentrations. In a single-dose group, there were no changes in serum creatinine values, while in a double-dose group there was a significant increase in serum creatinine concentration and a decrease in serum creatinine clearance. Risk factors for gentamicin nephrotoxicity were: through gentamicin concentration, older age and initial abnormal renal function. Ototoxic reaction developed in 35% of the patients on a single gentamicin dose and in 44.8% of the patients on a double dose (P > 0.05), and a lesion was more diffuse in this group. Risk factors for gentamicin ototoxicity were: through gentamicin concentration, duration of therapy, older age and abnormal renal function. Therapeutic effect was observed in 96% of the patients in SG and in 86.2% of the patients in DG (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effectiveness and adverse effects of a single daily dose of gentamicin versus twice daily administration]. 765 Oct 68

Cidofovir, (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine, is a novel antiviral nucleotide analogue with potent in vitro and in vivo activity against cytomegalovirus (CMV) and other herpesviruses. Thirty-one human immunodeficiency virus-seropositive patients with asymptomatic CMV excretion were evaluated in a phase I/II study with 2 regimens of cidofovir: cidofovir alone at doses of 0.5, 1.0, 3.0, or 10.0 mg/kg/week (20 patients) and cidofovir at 3.0, 5.0, or 7.5 mg/kg with concomitant oral probenecid, saline prehydration, extended dosing intervals, and drug interruption for proteinuria (19 patients). Prolonged and dose-dependent anti-CMV effect was observed with all cidofovir regimens > or = 3.0 mg/kg. The dose-limiting toxicity of cidofovir was dose- and schedule-dependent nephrotoxicity. Four of 20 patients had serum creatinine levels > or = 2.0 mg/dL after a mean cumulative exposure of 14.8 mg/kg cidofovir alone; however, none of 19 patients receiving the modified regimen had elevated creatinine (mean cidofovir exposure, 32.2 mg/kg). The clinical efficacy of cidofovir and its potential for cumulative nephrotoxicity needs further study in patients with end-organ CMV disease.
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PMID:(S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine (cidofovir): results of a phase I/II study of a novel antiviral nucleotide analogue. 770 4

Among a spectrum of renal disorders encountered in patients infected with the human immunodeficiency virus (HIV), the lesion studied most often has been the glomerular disease known as HIV-associated nephropathy. Of the other coincidental renal perturbations reported, the most significant are a heterogenous group encompassing potentially reversible acute renal failure (ARF), primarily acute tubular necrosis. While HIV-associated nephropathy may frequently be seen in asymptomatic HIV-seropositive individuals, acute tubular necrosis almost always is encountered in patients with clinical acquired immunodeficiency syndrome (AIDS). We analyzed our decade's experience in the management of 146 HIV disease patients with ARF (132 AIDS patients and 14 HIV-seropositive patients) and compared it with a contemporaneous group of 306 non-HIV subjects with ARF. All patients evaluated for ARF between January 1984 and December 1993 by the Renal Division at Kings County Hospital Center, Brooklyn, NY, were reviewed. Only those patients with ARF who reached a serum creatinine concentration of 530 mumol/L or higher were included in the analysis. Ninety-one percent of 146 HIV disease patients with ARF were less than 50 years old compared with only 33% of the 306 non-HIV subjects (P < 0.001). Septicemia was directly or indirectly responsible for 75% of patients with ARF in the AIDS group and for 39% in the non-HIV subjects (P < 0.006). Urinary tract obstruction was the cause of ARF in 54 of 306 (17%) non-HIV patients compared with none in the HIV group (P < 0.00001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Outcome of severe acute renal failure in patients with acquired immunodeficiency syndrome. 787 16

GLQ223 is a highly purified single-chain ribosome-inactivating protein with selective effects against a variety of cells, including macrophages infected with human immunodeficiency virus. We evaluated the safety, pharmacokinetics, and immunologic effects of multiple doses of GLQ223 in 22 patients with AIDS or AIDS-related complex; CD4+ T-cell counts were between 100 and 350/mm3. GLQ223 was administered intravenously at doses of 8, 16, 24, 36, and 50 micrograms/kg of body weight; the drug was administered by constant infusion over 3 h to achieve a concentration in serum of 50 ng/ml; this concentration is known to be associated with anti-HIV effects in vitro. All patients reported a flu-like syndrome characterized by muscle and joint aches and an increase in creatinine kinase levels; symptoms were controlled easily. For patients who received 36 and 50 micrograms/kg, target concentrations in serum were achieved and an increase in CD4+ and CD8+ T cells was sustained; this sustained increase persisted for at least 28 days after the last infusion. beta 2-Microglobulin levels increased during the infusions and then declined when the infusions ended. Repeat infusions of GLQ223 were safe and relatively well tolerated. The target concentration of GLQ223 in serum was achieved and sustained. Our results suggest that GLQ223 may have activity in treating patients with human immunodeficiency virus infection.
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PMID:Safety, activity, and pharmacokinetics of GLQ223 in patients with AIDS and AIDS-related complex. 791 Jul 22

Familiarity with renal issues that can challenge the care of patients with human immunodeficiency virus (HIV) should expedite diagnosis and therapeutic interventions. Among the most common problems are electrolyte and acid-base imbalances from many opportunistic infections or their treatments, including hyponatremia, hyperkalemia, hypokalemia, and hypo- and hypercalcemia. Acid-base disturbances, simple or mixed, can be due to underlying sepsis, opportunistic infections, or the therapy thereof. A recent report of seven patients with HIV with type B lactic acidosis failed to identify a satisfactory etiology. Elevations in creatinine or diminishing urine output should alert the physician to the possibilities of prerenal azotemia or acute tubular necrosis, which can result from progression of prerenal azotemia or can occur secondary to administered nephrotoxins, such as certain antibiotics and radiocontrast agents. Agents associated with nephrotoxicity include aminoglycosides, antifungal, antiviral, and radiocontrast agents, and nonsteroidal anti-inflammatory pain medications. Although prerenal azotemia and acute tubular necrosis are the most frequent causes of acute renal failure, the differential diagnosis should include acute interstitial nephritis, obstructive nephropathy, and glomerulopathies such as hemolytic uremic syndrome, thrombotic thrombocytopenia purpura, the newly described IgA nephropathy, and, in certain populations, HIV nephropathy.
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PMID:The spectrum of kidney diseases in patients with human immunodeficiency virus infection. 792 95


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