Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bloom syndrome (BS) is an autosomal recessive inherited disorder characterized by chromosomal instability leading to a high risk of cancer at an early age. The diagnosis should be considered in patients with short stature, photosensitivity, variable degrees of immunodeficiency, and hypogonadism. We report a 19-year-old woman, with history of dysmorphic features and recurrent infections. The diagnosis of bloom syndrome was made and confirmed cytogenetically at the age of 14 years. She developed a colon cancer revealed by venous thrombosis and anemia. She died after 15 days of the cancer diagnosis. This is the first registrated case of confirmed Bloom syndrome in Tunisian population.
 ...
PMID:Bloom syndrome complicated by colonic cancer in a young Tunisian woman. 2177 34

Human immunodeficiency virus (HIV) endocrinopathy encompasses a broad spectrum of disorders. Almost all the endocrine organs are virtually affected by HIV infection. HIV can directly alter glandular function. More commonly secondary endocrine dysfunction occurs due to opportunistic infections and neoplasms in immunocompromised state. The complex interaction between HIV infection and endocrine system may be manifested as subtle biochemical and hormonal perturbation to overt glandular failure. Antiretroviral therapy as well as other essential medications often result in adverse endocrinal consequences. Apart from adrenal insufficiency, hypogonadism, diabetes and bone loss, AIDS wasting syndrome and HIV lipodystrophy need special reference. Endocrinal evaluation should proceed as in other patients with suspected endocrine dysfunction. Available treatment options have been shown to improve quality of life and long-term mortality in AIDS patients.
 ...
PMID:Human immunodeficiency virus endocrinopathy. 2202 95

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive syndrome of chromosomal instability mainly characterized by microcephaly at birth, combined immunodeficiency and predisposition to malignancies. Due to a founder mutation in the underlying NBN gene (c.657_661del5) the disease is encountered most frequently among Slavic populations. The principal clinical manifestations of the syndrome are: microcephaly, present at birth and progressive with age, dysmorphic facial features, mild growth retardation, mild-to-moderate intellectual disability, and, in females, hypergonadotropic hypogonadism. Combined cellular and humoral immunodeficiency with recurrent sinopulmonary infections, a strong predisposition to develop malignancies (predominantly of lymphoid origin) and radiosensitivity are other integral manifestations of the syndrome. The NBN gene codes for nibrin which, as part of a DNA repair complex, plays a critical nuclear role wherever double-stranded DNA ends occur, either physiologically or as a result of mutagenic exposure. Laboratory findings include: (1) spontaneous chromosomal breakage in peripheral T lymphocytes with rearrangements preferentially involving chromosomes 7 and 14, (2) sensitivity to ionizing radiation or radiomimetics as demonstrated in vitro by cytogenetic methods or by colony survival assay, (3) radioresistant DNA synthesis, (4) biallelic hypomorphic mutations in the NBN gene, and (5) absence of full-length nibrin protein. Microcephaly and immunodeficiency are common to DNA ligase IV deficiency (LIG4 syndrome) and severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation due to NHEJ1 deficiency (NHEJ1 syndrome). In fact, NBS was most commonly confused with Fanconi anaemia and LIG4 syndrome. Genetic counselling should inform parents of an affected child of the 25% risk for further children to be affected. Prenatal molecular genetic diagnosis is possible if disease-causing mutations in both alleles of the NBN gene are known. No specific therapy is available for NBS, however, hematopoietic stem cell transplantation may be one option for some patients. Prognosis is generally poor due to the extremely high rate of malignancies.
 ...
PMID:Nijmegen breakage syndrome (NBS). 2237 3

Osteoporosis is common in human immunodeficiency virus (HIV)-infected persons. The etiology of osteoporosis in HIV-infected patients is likely multifactorial, involving traditional risk factors such as low body weight, hypogonadism, and smoking, as well as direct effects of chronic HIV infection and antiretroviral therapy. Emerging evidence suggests that the increasing prevalence of osteoporosis in HIV-infected persons translates into a higher risk of fracture, likely leading to excess morbidity and mortality as the HIV-infected population ages. This review addresses the epidemiology of osteoporosis, discusses the causes of low bone mineral density in HIV-infected persons, including the impact of specific antiretroviral therapies, and offers recommendations on screening and treating vitamin D deficiency and osteoporosis.
 ...
PMID:Bone loss in the HIV-infected patient: evidence, clinical implications, and treatment strategies. 2257 13

Selective androgen receptor modulators (SARMs) are androgens with tissue-selective activity. SARMs that have anabolic activity on muscle while having minimal stimulatory activity on prostate are classified as SARM agonists. They can be used to prevent the loss of lean body mass that is associated with cancer, immunodeficiency, renal disease and aging. They may also have anabolic activity on bone; thus, unlike estrogens, they may reverse the loss of bone strength associated with aging or hypogonadism. Our in-house effort on SARM program discovers a nonsteroidal androgen receptor ligand with a unique imidazolopyrazole moiety in its structure. In vitro, this compound is a weak androgen receptor binder and a weak androgen agonist. Despite this, in orchidectomized mature rats it is an effective SARM agonist, with an ED(50) on levator ani muscle of 3.3mg/kg and an ED(50) on ventral prostate of >30mg/kg. It has its maximal effect on muscle at the dose of 10mg/kg. In addition, this compound has mixed agonistic and antagonistic activities on prostate, reducing the weight of that tissue in intact rats by 22% at 10mg/kg. The compound does not have significant effect on gonadotropin levels or testosterone levels in both orchidectomized and intact male rats. It does not have notable progestin, estrogen or glucocorticoid agonistic or antagonistic activity in rats. In a female sexual behavior model, it improves the sexual desire of ovariectomized female rats for sexually mature intact males over nonsexually ovariectomized females. Overall, the imidazolopyrazole is a potent prostate-sparing candidate for development as a SARM agonist with an appropriate pharmacological profile for clinical benefit in muscle-wasting conditions and female sexual function disorders.
 ...
PMID:Pharmacological characterization of an imidazolopyrazole as novel selective androgen receptor modulator. 2309 93

Our research program was designed to assess androgenic, anabolic, and mood effects of testosterone replacement therapy in human immunodeficiency virus positive (HIV+) men with significant immune suppression and hypogonadism. This article focuses on mood effects. Treatment consisted of biweekly intramuscular injections of testosterone cypionate at doses of 200 to 400 mg. Assessments included psychiatric evaluation using the Structured Clinical Interview for DSM-III-R, Hamilton Rating Scale for Depression, and Brief Symptom Inventory. This is an interim report of 73 men who completed at least eight weeks of treatment. Responders continued for four more weeks and then entered a double-blind placebo controlled discontinuation phase.At study entry, 49% had CD4 counts under 50, and 84% had an acquired immune deficiency syndrome (AIDS)-defining condition. In terms of sexual desire and function, 76% were clear-cut responders at Week 8. Of the 31 study completers who had mood problems at baseline, 26 (84%) were rated as much improved in mood. Mean changes in CD4 cell count and beta 2 microglobulin after treatment were not statistically significant. These findings suggest that testosterone replacement therapy has significant antidepressant effects for men with significant immunodeficiency and clinical manifestations of hypogonadism.
...
PMID:Treatment of depression in HIV+men: Literature review and report of an ongoing study of testosterone replacement therapy. 2420 40

In recent years, the life expectancy for those living with human immunodeficiency virus (HIV) with access to combined antiretroviral therapy (cART) has increased. As men live longer, the role testosterone plays in sexual function as well as in general well-being is becoming increasingly important. Here we discuss the available literature concerning androgens and HIV disease. A review was undertaken by using a PubMed search with the umbrella terms HIV or AIDS and testosterone or androgens spanning 1985 to 2011. Significant articles found in references in the primary search were also included. The reported prevalence of androgen deficiency appears to be greater in HIV-infected males than in the general population. Androgen deficiency is usually associated with low luteinizing hormone and follicle-stimulating hormone and is sensitive to the type of measurement of testosterone used. Rates of hypogonadism may be falling since the advent of cART. Causes of low testosterone levels have been attributed to chronic illness, HIV replication, cART, opportunistic infections, comorbidities and coinfections, wasting, and normal age-related declines. Studies of testosterone treatment in HIV-positive men are lacking in standardization and outcome measures.
...
PMID:Hypogonadism in human immunodeficiency virus-positive men. 2446 91

Ataxia-telangiectasia-like disorder (ATLD) is a rare autosomal recessive disorder, and has symptoms similar to ataxia-telangiectasia (AT). ATLD is caused by mutations in the MRE11 gene, involved in DNA double-strand break repair (DSBR). In contrast to AT, ATLD patients lack key clinical features, such as telangiectasia or immunodeficiency, and are therefore difficult to be diagnosed. We report a female ATLD patient presenting with hypergonadotropic hypogonadism and hypersegmented neutrophils, previously undescribed features in this disorder, and potential diagnostic clues to differentiate ATLD from other conditions. The patient showed slowly progressive cerebellar ataxia from 2 years of age, and MRI revealed atrophy of the cerebellum, oculomotor apraxia, mild cognitive impairment, writing dystonia, hypergonadotropic hypogonadism with primary amenorrhea, and hypersegmented neutrophils. Western blot assay demonstrated total loss of MRE11 and reduction of ATM-dependent phosphorylation; thus, we diagnosed ATLD. Genetically, a novel missense mutation (c.140C>T) was detected in the MRE11 gene, but no other mutation was found in the patient. Our presenting patient suggests that impaired DSBR may be associated with hypergonadotropic hypogonadism and neutrophil hypersegmentation. In conclusion, when assessing patients with ataxia of unknown cause, ATLD should be considered, and the gonadal state and peripheral blood smear samples evaluated.
 ...
PMID:Hypergonadotropic hypogonadism and hypersegmented neutrophils in a patient with ataxia-telangiectasia-like disorder: potential diagnostic clues? 2473 32

Pharmacologic interventions for human immunodeficiency virus (HIV) wasting have been studied since the 1990s, but the results of these interventions have been difficult to compare because the studies used different HIV wasting definitions and assessed various patient outcomes. Thus, we performed a systematic review of the current literature to identify studies that evaluated pharmacologic management of HIV wasting and to compare and contrast treatment options. Further, we provide a comprehensive review of these treatment options and describe the definition of HIV wasting used in each study, the outcomes assessed, and whether antiretroviral therapy was used during the HIV wasting treatment. Literature searches of the PubMed/Medline (1946-2014) and Google Scholar databases were performed, and a review of the bibliographies of retrieved articles was performed to identify additional references. Only English-language articles pertaining to humans and HIV-infected individuals were evaluated. Thirty-six studies were identified that assessed pharmacologic interventions to treat HIV wasting. Appetite stimulants, such as megestrol acetate, have been shown to increase total body weight (TBW) and body mass index in HIV-infected patients with wasting. Studies evaluating dronabinol showed conflicting data on TBW increases, but the drug may have minimal benefit on body composition compared with other appetite stimulants. Testosterone has been shown to be effective in HIV wasting for those who suffer from hypogonadism. Recombinant human growth hormone has been evaluated for HIV wasting and has shown promising results for TBW and lean body mass increases. Thalidomide has been studied; however, its use is limited due to its toxicities. Although megestrol acetate and dronabinol are approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV wasting, it is important to recognize other comorbidities such as depression or hypogonadism that may contribute to the patient's appetite and weight loss. If a patient is diagnosed with hypogonadism and HIV wasting, testosterone would be a good therapeutic option. Although mirtazapine is not FDA approved for the management of HIV wasting, it has been shown to promote weight gain while treating depression symptoms. Mirtazapine may be a promising pharmacologic option in the management of HIV wasting and depression, but further research is needed.
...
PMID:Pharmacologic management of human immunodeficiency virus wasting syndrome. 2478 95

Androgen deficiency occurs frequently in men with human immunodeficiency virus (HIV) infection. Antiretroviral treatments had reduced the prevalence of male hypogonadism. The pathogenesis of testosterone (T) deficiency in HIV is multifactorial. Several mechanisms have been proposed; among them, drugs, fat redistribution, and a poor health status could explain the mechanism leading to gonadotropins inhibition and hypogonadotropic hypogonadism. The diagnosis of hypogonadism in HIV-infected men should be made based on clinical symptoms and a specific workup including T measurement. The interpretation of the results of biochemical testing is more difficult in men with HIV due to several confounding factors. T treatment should be offered to HIV-infected men with documented clinical hypogonadism and symptoms, especially if they are losing lean mass.
...
PMID:Hypogonadism in the HIV-infected man. 2516 63


<< Previous 1 2 3 4 5 Next >>