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)

Women with transfusion dependent thalassaemia suffer from failure of pubertal growth and delayed onset of menarche with amenorrhea, anovulation and infertility. With improved pediatric and hematological care is now possible, for patients with b thalassaemia, to achieve a pregnancy. Pre-pregnancy assessment included checks for hypothyroidism and diabetes, for hepatitis B and C, human immunodeficiency virus, Rubella, cardiac functions, liver functions by estimating aspartate and alanine aminotransferases, gamma-glutamyl transpeptidase, alkaline phospatase, and total plasma proteins. The frequency of blood transfusion needed to be increased in order to maintain the hemoglobin concentration above 10 g/dl. Desferroxamine must be stopped as soon as pregnancy is diagnosed continuing the administration of the folic acid supplements throughout pregnancy. Desferroxamine will be resumed after delivery. The safety of iron chelation with desferroxamine during the periconceptional period and pregnancy has not yet been established. Some animal studies have shown skeletal anomalies; other published studies report seven women with b thalassaemia major who became pregnant while taking desferroxamine: all the women had normal babies. The mode of delivery is usually vaginal, while Cesarean section is performed in those cases with pre-eclampsia, fetal distress, cephalopelvic dysproportion, slow progression of labor, as in women without thalassaemia. In conclusion, with the advent of regular blood transfusion associated with iron chelation therapy, pregnancy in b thalassaemia can be safe for mothers and their babies with appropriate care.
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PMID:[Pregnancy in women with thalassaemia]. 1139 93

Interleukin-1 receptor antagonist (IL-1RA) is a naturally occurring competitive inhibitor of interleukin-1 (IL-1)-induced proinflammatory activity. The IL-1RA gene is polymorphic, resulting in quantitative differences in both IL-1RA and IL-1beta production. Persons homozygous for allele 2 of the IL-1RA gene (IL1RN*2) have a more prolonged and more severe proinflammatory immune response than persons with other IL-1RA genotypes. Thus, being IL1RN*2 homozygous might be beneficial when combating infectious agents or malignantly transformed cells, but it might be detrimental for those with chronic inflammatory conditions or who are pregnant. The IL1RN*2 phenotype is associated with ulcerative colitis and Crohn's disease, lupus erythematosus, vulvar vestibulitis, and possibly with osteoporosis and coronary artery disease. IL1RN*2 homozygosity may also be associated with recurrent spontaneous abortion, preterm birth, and severity of preeclampsia. Conversely, there are negative associations between IL1RN*2 homozygosity and vaginal colonization with mycoplasmas, infection with human cytomegalovirus and Epstein-Barr virus, human immunodeficiency virus proliferation, and the occurrence of ovarian cancer.
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PMID:Influence of interleukin-1 receptor antagonist gene polymorphism on disease. 1174 Jul 9

Alpha-fetoprotein (AFP) was 1 of the first serum protein markers to serve in the dual capacities of tumor marker and fetal defect marker, ie, an oncofetal protein, in the clinical laboratory. Although the serum-marker capacity of AFP has long been used, less is known of the fluid compartments of this oncofetal protein during fetal and perinatal development. In this review, the biologic activities of AFP are discussed in light of its presence in the various biologic fluid compartments: fetal serum, amniotic fluid, cord blood, urine, and maternal serum. AFP concentrations within the biologic fluids are considered in the context of gestational age, sex, body weight, and anatomic location. Discussion follows concerning the relationships and roles of AFP in various developmental disorders such as hypothyroidism, folate deficiencies, autoimmune disorders, acquired immunodeficiency disorder (AIDS), congenital heart defects, cystic fibrosis, preeclampsia/hypertension, and platelet aggregation disorders. Based on its presence in so many types of birth defects, malformations, and congenital anomalies, AFP can be seen to serve as a form of molecular "duct tape" during pregnancy and postnatal development.
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PMID:Levels of alpha-fetoprotein during pregnancy and early infancy in normal and disease states. 1466 62

The pathogenesis of preeclampsia stems from aberrant changes at the placental interface. The trophoblastic endovascular invasion of tonic spiral arteries that converts them to passive conduits falters. Uteroplacental insufficiency and fetoplacental hypoxemia result. Secondary maternal oxidative stress and an excessive inflammatory response to pregnancy generate the clinical syndrome of preeclampsia. Current treatment focuses on preventing seizures, controlling hypertension, preserving renal function and delivering the baby. We propose that the pathophysiological changes induced by preeclampsia in the placenta parallel those caused by persistent hypoxemia in the lungs at high altitude or with chronic obstructive pulmonary disease. Unrelenting pulmonary hypoxic vasoconstriction induces pulmonary hypertension and cor pulmonale. Inhalation of nitric oxide and phosphodiesterase-5 inhibitors opposes pulmonary hypoxic vasoconstriction, alleviates pulmonary hypertension and improves systemic oxygenation. Notably nitric oxide donor therapy also counters hypoxemic fetoplacental vasoconstriction, a biological response analogous to pulmonary hypoxic vasoconstriction. Fetal oxygenation and nutrition improve. Placental upstream resistance to umbilical arterial blood flow decreases. Fetal right ventricular impedance falls. Heart failure (cor placentale) is avoided. Emergency preterm delivery can be postponed. Other than low dose aspirin and antioxidants vitamins C and E no available therapy specifically targets the underlying disease profile. We hypothesize that, like nitric oxide donation, pharmacological inhibition of placental phosphodiesterase-5 will also protect the fetus but for a longer time. Biological availability of guanosine 3'5'-cyclic monophosphate is boosted due to slowed hydrolysis. Adenosine 3'5'-cyclic monphosphate levels increase in parallel. Cyclic nucleotide accumulation dilates intact tonic spiral arteries and counters hypoxemic fetoplacental vasoconstriction. Intervillous and intravillous perfusion pick up. Maternal to fetal placental circulatory matching improves. Enhanced placental oxygen uptake alleviates hypoxemic fetal stress. Appropriate fetal nutrition resumes. Cor placentale and severe intrauterine growth restriction are averted. Increased maternal cyclic nucleotide concentrations promote systemic vasodilatation so that blood pressures fall. Preemption of oxidative stress initiated by "consumptive" oxidation of nitric oxide stabilizes the vascular endothelium and corrects coagulopathy. Anti-inflammatory and immunosuppressant adenosine 3'5'-cyclic monphosphate offsets the extreme gestational inflammatory response. Cellular injury and multi-organ damage are prevented. One tablet a day of the new long acting phosphodiesterase-5 inhibitor, tadalafil (half life of 17.5 h) theoretically should allow a preterm pregnancy affected by preeclampsia to continue safely. Selective monitoring of vital organ functions guards against life-threatening maternal complications. Regular biophysical profiling warns the obstetrician of impending fetal compromise. Fetal growth and vital organ maturation can continue. As a result workloads imposed upon neonatal intensivists will lighten. Parental anxiety and concern will be allayed. The cost of treating preeclamptic mothers and their extremely low birth weight infants will decrease. Money saved by midwifery services in poorer states can be used to pay for better prenatal care. Severe preeclampsia/eclampsia will be less common. Maternal and perinatal morbidity and mortality will be reduced. Because the human immunodeficiency virus often infects individuals at a workforce eligible age, the global acquired immunodeficiency syndrome pandemic has already brought many nations to the brink of economic ruin. Potentially productive lives saved for the future will help restore them fiscally.
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PMID:Hypothesis: selective phosphodiesterase-5 inhibition improves outcome in preeclampsia. 1550 76

An increased incidence of thrombotic thrombocytopenic purpura has been reported among human immunodeficiency virus-infected patients or those with acquired immunodeficiency syndrome (AIDS). Despite this association, hitherto only a single case of thrombotic thrombocytopenic purpura has been reported in an HIV-infected patient during pregnancy. We describe a young multiparous patient with long-standing AIDS who presented with lower abdominal pain. Following findings of thrombocytopenia, microangiopathic hemolytic anemia, renal failure, low-grade fever, and mental status changes, thrombotic thrombocytopenic purpura was diagnosed after initially considering the diagnosis of severe preeclampsia, and the patient was delivered by cesarean section. The patient required multiple plasma exchanges during a protracted postpartum course, and was discharged in good health. This first report of thrombotic thrombocytopenic purpura and AIDS in pregnancy demonstrates that when encountering preeclampsia in patients with AIDS, thrombotic microangiopathy should be strongly considered. In addition, these patients may exhibit an attenuated response to plasma exchange therapy and despite previous reports in nonobstetric patients, a favorable outcome is attainable in these critically ill patients.
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PMID:Thrombotic thrombocytopenic purpura in a patient with acquired immunodeficiency syndrome at 28 weeks gestation. 1590 17

Preeclampsia is a multifactorial pregnancy-specific disease. In some cases, severe preeclampsia and related disorders of acute fatty liver of pregnancy and hemolysis, elevated liver enzymes, low platelets syndrome are associated with inherited defects in mitochondrial beta-oxidation of fatty acids, especially a deficiency of long-chain 3-hydroxyacyl coenzyme A dehydrogenase (LCHAD). Recently, an unexplained increase in the incidence of preeclampsia has been documented in human immunodeficiency virus (HIV)-infected pregnant women on treatment with highly active antiretroviral therapy (HAART). We performed this study to determine if antiretroviral drugs affect mitochondrial beta-oxidation fatty acids in vitro. Two normal and 1 heterozygous LCHAD-deficient cell lines were exposed to up to 5 times the therapeutic concentrations of the following antiretroviral drugs: nevirapine, didanosine, lamivudine, and a combination of nelfinavir, zidovudine, and lamivudine. One homozygous LCHAD-deficient cell line served as the positive control. After exposure of the fibroblasts to these drugs for periods ranging from 2 to 10 days, accumulations of even-chain 3-hydroxy fatty acids (3-OH-C6 to 3-OH-C18) in the culture media were measured by stable-isotope dilution gas chromatography/mass spectrometry. Compared to the respective unexposed fibroblasts, there was no significant build-up of 3-hydroxy fatty acids in the culture media of normal or heterozygous LCHAD-deficient fibroblasts exposed to antiretroviral drugs. Our results show that the commonly used antiretroviral drugs do not adversely affect fatty acid oxidation in fibroblasts. Therefore, an altered fatty acid oxidation may not be the mechanism for the reported increased risk of preeclampsia in HIV-infected pregnant women on HAART.
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PMID:Highly active antiretroviral therapy does not affect mitochondrial beta-oxidation of fatty acids: an in vitro study in fibroblasts. 1824 Aug 71

Management of pregnancies with human immunodeficiency virus, haemolytic anaemia, elevated liver enzymes, low platelets (HELLP) syndrome, and low platelets presents complexities in investigations and treatments, because these conditions and their treatment affect the mother and baby. Low platelets in severe pre-eclampsia, eclampsia and HELLP syndrome are relatively common, and should be detected early once the diagnosis of pre-eclampsia, HELLP syndrome, or both, are made. The mainstay of treatment is lowering of high blood pressure with rapid-acting antihypertensive agents, prevention of convulsions or further seizures with MgSO(4), use of steroids for fetal lung maturity if necessary, followed by delivery of the baby. The use of high-dose steroids for the rapid recovery of maternal platelet counts is controversial, and should not be used routinely in women with HELLP syndrome. The use of platelet transfusion in women with severe pre-eclampsia, eclampsia and HELLP syndrome is a temporising measure, and should only be justified if the clinical circumstances warrant their use (e.g. before caesarean section when the woman has a low platelet count with evidence of bruising or bleeding from venepuncture sites). Low platelets may be an isolated finding in asymptomatic pregnant women and warrant the offer of a human immunodeficiency virus test, as it may be the first sign of this infection. Isolated low platelets may also indicate gestational thrombocytopaenia or idiothrombocytopaenic purpura. Gestational thrombocytopaenia is a benign condition and a diagnosis of exclusion. All clinicians should be aware that low platelets warrant further investigations because of the above-mentioned issues.
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PMID:Managing pregnancy with HIV, HELLP syndrome and low platelets. 2210 81

To describe appropriate maternal and obstetrical indications for primary cesarean delivery. The list of potential indications is long. Among all maternal and obstetrical indications, labor dystocia is the most common; multifetal pregnancy and malpresentation are not infrequent. Maternal indications, including human immunodeficiency virus (with high viral load) and herpes simplex virus (with active lesions), are rare. Preeclampsia alone typically is not an appropriate indication for cesarean delivery. Although the need for a cesarean is absolute for some conditions, such as complete placenta previa or placenta accreta, minimum criteria for a cesarean are variable and subjective for many indications, including dystocia. The subjective diagnosis of labor dystocia provides the best opportunity to prevent the first cesarean.
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PMID:When is primary cesarean appropriate: maternal and obstetrical indications. 2300 63

The dire conditions of the human immunodeficiency virus/acquired immune deficiency syndrome epidemic and the immense benefits of antiretroviral prophylaxis in prevention of mother-to-child transmission far outweigh the potential for adverse effects and undeniably justify the rapid and widespread use of this therapy, despite incomplete safety data. Highly active antiretroviral therapy has now become standard care, and more than half the validated regimens include protease inhibitors. This paper reviews current knowledge of the safety of these drugs during pregnancy, in terms of maternal and fetal outcomes. Transfer of protease inhibitors across the placenta is known to be minimal, and current data about birth defects and fetal malignancies are reassuring. Maternal liver function and glucose metabolism should be monitored in women treated with protease inhibitor-based regimens, but concerns about the development of maternal resistance, should treatment be discontinued, have been shown to be groundless. Neonates should be screened for hematologic abnormalities, although these are rarely severe or permanent and are not usually related to the protease inhibitor component of the antiretroviral combination. Current findings concerning pre-eclampsia and growth restriction are discordant, and further research is needed to address the question of placental vascular complications. The increased risk of preterm birth attributed to protease inhibitors should be interpreted with caution considering the discrepant results and the multitude of confounding factors often overlooked. Although data are thus far reassuring, further research is needed to shed light on unresolved controversies about the safety of protease inhibitors during pregnancy.
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PMID:Safety of protease inhibitors in HIV-infected pregnant women. 2410 83

Haemodynamic and cardiac structural changes in severe pre-eclampsia and in pregnant women with human immunodeficiency virus (HIV) infection have not been clearly established. We performed transthoracic echocardiography on 105 women. Women with pre-eclampsia demonstrated (mean (SD), untreated vs treated) preserved fractional shortening (40 (7.1)% vs. 41 (8.6)%), a non-dilated left ventricle (4.5 (0.49) cm vs. 4.4 (0.44) cm), increased mitral valve E/septal e' (10.5 (3.3) vs. 10.6 (2.8)), and preserved tricuspid annular plane systolic exertion (2.6 (0.36) cm vs. 2.4 (0.51) cm). Women with HIV infection demonstrated (mean (SD), HIV-positive vs healthy) a reduced cardiac index (2.8 (0.64) ml.min(-1) .m(-2) vs. 3.1 (0.7) ml.min(-1) .m(-2) , p = 0.029), reduced septal s' tissue Doppler velocity (8.5 (1.5) cm.s(-1) vs. 9.3 (1.7) cm.s(-1) , p = 0.042), increased left ventricular end-diastolic area (7.6 (2.1) cm2 vs. 6.3 (1.7) cm2 , p = 0.004), and reduced right ventricular s' and e' velocity (s' velocity 14.7 (3.1) cm.s(-1) vs. 7.0 (2.9) cm.s(-1) p = 0.001, e' velocity 16.3 (4.1) cm.s(-1) vs. 18.7 (3.4) cm.s(-1) , p = 0.013). The mitral value E/septal e' was > 8 in 39% of patients with HIV. Fractional shortening (< 28%) was reduced in 10% of healthy women, and mitral valve E/septal e' ratios were > 8 in 38% of that group. Women with pre-eclampsia demonstrated preserved systolic function, with diastolic dysfunction. Women with HIV demonstrated reduced left and right ventricular systolic function, with increased ventricular dilatation.
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PMID:Transthoracic echocardiographic assessment of haemodynamics in severe pre-eclampsia and HIV in South Africa. 2589 69


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