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)

5' GTGGTGGGTGGGTGGGT-3' (AR177) is a 17-mer oligonucleotide with anti-human immunodeficiency virus (HIV) activity that is composed of a phosphodiester backbone and single phosphorothioate linkages at the 3' and 5' ends. A hemodynamic toxicity study was conducted in which cynomolgus monkeys were infused i.v. over a 10-minute period with single doses of 5, 20 or 50 mg AR177/kg or saline. Blood pressure, ECG, clinical chemistry, hematology, complement factors, coagulation parameters and the AR177 plasma concentration were determined. AR177 did not cause any mortality in this study, nor did it cause changes in blood pressure, ECG, clinical chemistry or hematology parameters at any dose. There was a minimal, dose-dependent increase in the levels of complement split product Bb and total hemolytic complement. There was a significant dose-dependent and reversible inhibition of coagulation with the 20- and 50-mg/kg doses that lasted up to several hours after infusion. The time course of the inhibition of coagulation closely matched the plasma levels of AR177. There was a no-effect plasma AR177 concentration vs. activated partial thromboplastin time of approximately 60 to 100 micrograms AR177/ml, above which there was prolongation of activated partial thromboplastin time. These data demonstrate that AR177 does not cause significant hemodynamic toxicity at the doses studied and that this drug could be administered as a rapid infusion without any acute, life-threatening effects at doses that produce plasma concentrations that have shown anti-HIV activity in vitro.
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PMID:Single-dose hemodynamic toxicity and pharmacokinetics of a partial phosphorothioate anti-HIV oligonucleotide (AR177) after intravenous infusion to cynomolgus monkeys. 881 16

5'GTGGTGGGTGGGTGGGT-3' (AR177) is a partial phosphorothioate, 17-mer oligonucleotide that has been shown to have anti-human immunodeficiency virus (HIV) activity in vitro and to be a potent inhibitor of HIV-1 integrase. A repeat-dose toxicity and pharmacokinetic study was conducted in which cynomolgus monkeys were given bolus i.v. injections of 2.5, 10 or 40 mg AR177/kg/day every other day for a total of 12 doses. Control monkeys received saline. ECG, clinical chemistry, hematology, coagulation parameters, histopathology and the AR177 plasma concentration were evaluated. AR177 did not cause any mortality in this study, nor did it cause changes in ECG, clinical chemistry, hematology values or histology. However, there was a dose-dependent inhibition of coagulation measured by a prolongation of activated partial thromboplastin time; this inhibition was reversible with drug washout. Analysis of plasma samples by HPLC demonstrated that there was no difference between the AR177 plasma concentrations that were achieved after the 1st and 12th (last) doses of 2.5, 10 or 40 mg/kg. There was a direct relationship between the AR177 plasma concentration and activated partial thromboplastin time. These results indicate that repeated bolus i.v. administration of AR177 to cynomolgus monkeys at doses as high as 40 mg/kg was well tolerated and was not associated with the serious cardiovascular responses previously observed with other oligonucleotides administered i.v.
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PMID:Repeat-dose toxicity and pharmacokinetics of a partial phosphorothioate anti-HIV oligonucleotide (AR177) after bolus intravenous administration to cynomolgus monkeys. 881 17

The human immunodeficiency virus (HIV) infection is becoming more complex. Hemostatic abnormalities occur frequently in the patient with HIV. HIV-related thrombocytopenia (Tr-HIV) is the most common hemostatic disorder with a high morbidity and affects patients from every risk group independently of age, sex, or stage of infection. Two mechanisms are responsible for the Tr-HIV: bone marrow failure and immunological disorders, namely, circulating immune complex deposited on the platelet membrane and the production of autoantibodies directed against platelets. The treatment of choice is zidovudine; other available options are not as effective as zidovudine. In addition, there are some abnormalities in the fluid phase of the coagulation cascade which can produce bleeding or thrombosis in the HIV patient. The most common are a prolonged partially activated thromboplastin time test, the production of a lupic anticoagulant and anticardiolipin antibodies, and several abnormalities in the natural-occurring anticoagulants. The thrombotic thrombocytopenic purpura recently associated with HIV has a clinical presentation and treatment alternatives that closely resemble those for the classical disease. The knowledge of these hemostatic abnormalities in the HIV seropositive patient allows a more rational care of these patients.
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PMID:[Changes in blood coagulation in HIV infection]. 922 57

A polysaccharide extracted from the leaf of Rhizophora apiculata (RAP) was assessed in cell culture systems, for its activity against human and simian immunodeficiency viruses. RAP inhibited HIV-1 or HIV-2 or SIV strains in various cell cultures and assay systems. It blocked the expression of HIV-1 antigen in MT-4 cells and abolished the production of HIV-1 p24 antigen in peripheral blood mononuclear cells (PBMC); the 50% effective concentration (EC50) of RAP in HIV-1 infected MT-4 cells and in PBMC was 10.7 and 25.9 microg/ml, respectively. RAP (100 microg/ml) completely blocked the binding of HIV-1 virions to MT-4 cells. RAP also reduced the production of viral mRNA when added before virus adsorption. RAP inhibited syncytium formation in cocultures of MOLT-4 cells and MOLT-4/HIV-1(IIIB) cells. RAP did not prolong activated partial thromboplastin time (APTT) up to 500 microg/ml. These properties may be advantageous should RAP be considered for further development.
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PMID:Antiviral properties of a mangrove plant, Rhizophora apiculata Blume, against human immunodeficiency virus. 1066 61

A 70-year-old patient with a history of hypertension and hypercholesterolemia was referred for evaluation of necrotic toes. The patient had a history of several cerebrovascular accidents during the previous month. Initially, she developed sudden-onset left upper extremity weakness which, over the ensuing 4 days, progressed to complete left-sided weakness. This was followed by the development of acute dysarthria. A transesophageal echocardiogram revealed moderate left ventricular hypertrophy, several vegetations on her tri-leaflet aortic valve associated with moderate aortic regurgitation, and a large right atrial thrombus with a mobile component. Bubble studies failed to reveal any septal defects. The patient's electrocardiogram was nonspecific. As serial blood cultures were negative despite fevers of up to 39.8 degrees C, the patient was treated with a 6-week course of intravenous ceftriaxone, ampicillin, gentamicin, and ciprofloxacin for a presumed diagnosis of culture-negative endocarditis. Fungal cultures of the blood were negative. The patient, however, progressed and developed several necrotic toes. Physical examination was significant for ischemic changes of the left first, second, third, and fifth toes, as well as the right first and second toes. Diffuse subungual splinter hemorrhages in the toenails, numerous 2-4-mm palpable purpuric papules on the lower extremities, and nontender hemorrhagic lesions of the soles were also noted. Peripheral and carotid pulses were intact and no carotid bruits were heard. Cardiopulmonary and abdominal examinations were unremarkable. Neurologic examination revealed a disoriented, dysarthric patient with left central facial nerve paralysis, as well as spasticity, hyperactive reflexes, and diminished strength and sensation in the left upper and lower extremities. A left visual field defect and left hemineglect were also present. The patient's last brain computerized tomogram revealed areas of low attenuation consistent with cerebral infarctions in three distinct areas of the brain. These included the left occipitotemporal area, the right parieto-occipital area, and the right posterior frontal region. The regions affected were in the distribution of both the anterior and posterior circulation. No evidence of hemorrhage was noted. The patient subsequently complained of abdominal discomfort. A computerized tomogram of the abdomen with oral and intravenous contrast revealed a 4-cm x 3-cm irregular mass in the tail of the pancreas with several low-attenuation lesions throughout the liver which were consistent with infarctions or metastases. Several splenic infarctions were also present. A biopsy of the tumor revealed pancreatic adenocarcinoma. The patient's carcinoembryonic antigen level was 18. 4 ng/mL (0-3) and the CA 19-9 antigen level was 207,000 U/mL (0-36). The alpha-fetoprotein level was normal. Other significant laboratory findings included a prothrombin time of 16.7 (international normalized ratio, 1.4), an activated partial thromboplastin time of 32 (ratio, 1.3), and a platelet count of 85,000/mm3. The Russell viper venom time, sedimentation rate, and C3 levels were normal, and the patient was negative for antinuclear antibodies, anticardiolipin antibodies, and antibodies to extractable nuclear antigens. Of note, the patient was not receiving any anticoagulation. Blood cultures for mycobacteria and fungi, human immunodeficiency virus serology, and urinalysis and culture were negative. The patient subsequently developed an inferior wall myocardial infarction and was transferred to the coronary care unit. In line with the family's request, aggressive care was ceased and the patient expired. The patient's family refused an autopsy.
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PMID:Cutaneous manifestations of marantic endocarditis. 1080 80

Anemia, thrombocytopenia, and neutropenia are common manifestations in patients with human immunodeficiency virus infection that become more frequent and severe with progression from the asymptomatic state to acquired immunodeficiency syndrome (AIDS). Causes of anemia in AIDS include nutritional deficiencies, infection, and marrow suppression by antiretroviral drugs and by the disease itself. Autoimmune hemolysis and blood loss from gastrointestinal lymphoma or Kaposi sarcoma may also contribute. Granulocytopenia may be due to infection, autoimmunity, or bone marrow suppression by drugs or the immunodeficiency virus. Lymphopenia, the classic hallmark of the disease, typically affects T-helper cells first and worsens as the disease advances. Lymphopenia is a result of the direct cytopathic effects of the virus. Thrombocytopenia can occur from antibodies causing an idiopathic thrombocytopenic purpura-like state from bone marrow suppression or from thrombotic thrombocytopenic purpura. A prolonged partial thromboplastin time due to a coagulopathy caused by lupus anticoagulant causing has been described. A variety of malignancies occurs.
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PMID:Hematological Effects of Human Immunodeficiency Virus Infection. 1088 19

Many aspects of acquired immunodeficiency syndrome (AIDS) have been described in detail in the literature. However, there have been very few articles on the phenomenon of deep vein thrombosis (DVT) in the lower extremities of human immunodeficiency virus (HIV)/AIDS patients. The objective of this communication is to record the incidence of DVT in HIV/AIDS patients and the risks for development of embolic events and to emphasize the need for prevention and for the vigorous treatment of this complication. We conducted a retrospective review of HIV/AIDS-infected patients with DVT admitted to Mount Sinai School of Medicine/Cabrini Hospital in New York during the last 5 years. Analysis includes demographic data; risk factors for HIV/AIDS infection; associated medical problems; recent surgery; and laboratory findings including CD4 counts, platelet counts, prothrombin times, partial thromboplastin times, and plasma albumin levels; and image studies. From January 1995 to January 2000 4752 HIV/AIDS-infected patients were admitted. Of those admitted to the hospital 45 (0.95%) were found to have DVT. There were 36 males and nine females (mean age 43 years). Of the 45 patients 38 had infectious complications and 13 developed a malignancy. The distribution of the thromboses were the femoral vein in 23 patients, the popliteal vein in 20 patients, and the iliofemoral system in 2 patients. Twelve patients had recurrent DVT and three patients developed a pulmonary embolism. HIV/AIDS infection is a considerable risk for development of DVT in the lower extremity. Statistically DVT in HIV/AIDS is approximately 10 times greater than in the general population. Emphasis upon prevention and vigorous treatment of DVT is recommended.
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PMID:HIV/AIDS and the risk of deep vein thrombosis: a study of 45 patients with lower extremity involvement. 1145 Jul 80

Hirudin, the anticoagulatory polypeptide of the leech Hirudo medicinalis, strongly inhibits thrombus formation by specifically interacting with thrombin. For diagnostic purposes, hirudin should be superior to other anticlotting compounds because it only minimally alters the mineral, protein, and cellular blood constituents. To test this hypothesis, hirudinized and routinely processed venous blood from 80 healthy volunteers and patients was subjected to a variety of automated blood tests. A strong correlation was found between the results of automated complete blood counts obtained from K(2)-ethylenediaminetetraacetic acid (EDTA) anticoagulated and hirudinized blood (1000 antithrombin units [ATU] hirudin/ml). In addition, clinical chemistry and serological infection parameters (asparlat amintransferase [ASAT], lactate dehydrogenase [LDH], sodium, and so on, and antibodies against hepatitis B and C and human immunodeficiency virus [HIV]1/2, respectively) correlated well when measured in serum as compared with hirudinized plasma. Contrary to single clotting factors, global coagulation parameters (activated partial thromboplastin time [aPTT], prothrombin time [PT]) could not be measured in hirudinized blood. Recombinant hirudin neither interfered with immunophenotyping of mononuclear cells using FACScan analysis, nor did it alter the detection of Wilms' tumor gene expression by RT-PCR technology even at high doses (5000 ATU hirudin). Thus, a hirudin-containing blood sampling tube can be designed as a universal blood sampling tube (UBT) for testing the majority of diagnostic blood parameters.
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PMID:Measurement of hematological, clinical chemistry, and infection parameters from hirudinized blood collected in universal blood sampling tubes. 1154 57

Three neutralizing monoclonal antibodies (MAbs), 2G12, 2F5, and 4E10, with activity in vitro and in vivo were administered in an open-label, nonrandomized, proof-of-concept study to attempt to prevent viral rebound after interruption of antiretroviral therapy (ART). Ten human immunodeficiency virus type 1-infected individuals identified and treated with ART during acute and early infection were enrolled. The first six patients were administered 1.0 g of each of the three MAbs per infusion. The remaining four patients received 2G12 at 1.0 g/infusion and 2.0 g/infusion of 2F5 and 4E10. The MAbs were well tolerated. Grade I post-partial thromboplastin time prolongations were noted. Viral rebound was observed in 8/10 subjects (28 to 73 days post-ART interruption), and 2/10 subjects remained aviremic over the course of the study. In seven of eight subjects with viral rebound, clear resistance to 2G12 emerged, whereas reductions in the susceptibilities of plasma-derived recombinant viruses to 2F5 and 4E10 were neither sustained nor consistently measured. Viral rebound was associated with a preferential depletion of CD4(+) T cells within the gastrointestinal tract. Though safe, the use of MAbs generally delayed, but did not prevent, virologic rebound. Consideration should be given to further pilot studies with alternative combinations of MAbs and perhaps additional novel treatment modalities.
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PMID:Adjunctive passive immunotherapy in human immunodeficiency virus type 1-infected individuals treated with antiviral therapy during acute and early infection. 1768 78

The 22q11.2 deletion syndrome (22q11DS) is a common genetic disease characterized by broad phenotypic variability. Despite the small number of studies describing hematological alterations in individuals with 22q11DS, it appears that these abnormalities are more frequent than previously imagined. Thus, the objective of our study was to report on a patient with 22q11DS presenting thrombocytopenia and large platelets and to review the literature. The patient, a 13-year-old boy, was originally evaluated due to craniofacial dysmorphia and speech delay. He also had a history of behavioral changes, neuropsychomotor delay and recurrent otitis/sinusitis. The identification of a 22q11.2 microdeletion by fluorescent in situ hybridization diagnosed the syndrome. Despite his hematological alterations, he only had a history of epistaxis and bruising of the upper and lower limbs. Assessments of the prothrombin time, thrombin time, partial thromboplastin time, bleeding time, fibrinogen levels and platelet aggregation (including the ristocetin induced platelet aggregation test) were all normal. Hematological alterations observed in 22q11DS are directly related to the genetic disorder itself (especially in respect to deletion of the GPIb gene) and secondary to some clinical findings, such as immunodeficiency. Macrothrombocytopenia is increasingly being considered a feature of the broad spectrum of 22q11DS and may potentially be a clinical marker for the syndrome.
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PMID:Hematological abnormalities and 22q11.2 deletion syndrome. 2328 64


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