Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tropical spastic paraparesis or HTLV-I-associated myelopathy is a progressive spastic disorder associated with the human T-lymphotropic virus type I. Some cases have responded to prednisone. Danazol is an attenuated androgen with minimal virilizing effects. It is used in the treatment of endometriosis and various autoimmune hematologic diseases shown to be responsive to prednisone. Because danazol is anabolic, useful in prednisone-responsive diseases, and less toxic than prednisone, we gave danazol to 6 patients with TSP and 1 with HIV, HTLV-I-associated myelopathy. Five patients had a favorable response. Two became ambulatory after having been confined to a wheelchair. Three were able to ambulate greater distances (in walkers) than prior to danazol. Three had noticeable decreases in spasticity. Urinary incontinence resolved in two. Physical therapy was variably employed in all except one patient. Two patients who had not responded to physical therapy responded to physical therapy and danazol. One patient did not tolerate danazol and one patient did not improve. Toxicities noted were mild elevations in liver enzymes in 4 patients; these responded to a decrease in dose of danazol; amenorrhea in one and mild fluid retention in one. We conclude that danazol is a useful agent in the management of TSP.
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PMID:Tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM): treatment with an anabolic steroid danazol. 181 44

Incubation of highly enriched neurons from rat cerebral cortex with the human immunodeficiency virus type 1 (HIV-1) coat protein gp120 for 18 h results in fragmentation of DNA at internucleosomal linkers, a feature of apoptosis. We report that neurons respond to exposure to gp120 with an increased release of arachidonic acid via activation of phospholipase A2. This process is not inhibited by antagonists of the N-methyl-D-aspartate (NMDA) receptor channels. To investigate the influence of arachidonic acid on the sensitivity of NMDA receptor towards its against, low concentrations of NMDA were coadministered with arachidonic acid. Under these conditions the NMDA-mediated cytotoxicity was enhanced. We conclude that gp120 causes an activation of phospholipase A2, resulting in an increased release of arachidonic acid which in turn sensitizes the NMDA receptor. Two compounds were found to act cytoprotectively against the deleterious effect caused by gp120 on neurons: Memantine [1-amino-3,5-dimethyladamantane] and Flupirtine [2-amino-3-ethoxycarbonylamino-6-(4-fluoro-benzyl-amino)-pyridine maleate]. Both compounds have been found to display a potent cytoprotective effect on neurons treated with the excitatory amino acid NMDA or with the human immunodeficiency virus type 1 (HIV-1) coat protein gp120. The NMDA antagonist Memantine, a drug currently used in the therapy of spasticity and Parkinson's disease, prevented the effects of gp120 at micromolar concentrations. Flupirtine was previously found to be a centrally acting, nonopiate analgesic agent which additionally possesses anticonvulsant and muscle-relaxant activity at doses similar to those producing analgesia. The cytoprotective effect of Flupirtine in vitro was significant (above 10 microM). Considering the fact that both Memantine and Flupirtine display almost no clinical side effects, these drugs may prove useful both in preventing primary infection of brain cells with the HIV virus, as well as in treating the neurological disorders often associated with the immunodeficiency syndrome such as AIDS-related dementia.
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PMID:Neurotoxicity in rat cortical cells caused by N-methyl-D-aspartate (NMDA) and gp120 of HIV-1: induction and pharmacological intervention. 882 91

Lower extremity symptoms are caused by lesions at any level of the neuraxis, from cortex to muscle. HIV affects virtually every level of the nervous system, either directly or indirectly. The presence of pathology at multiple levels and by multiple processes further complicates the bedside diagnosis of a patient with AIDS and neurologic symptoms. Many neuropathies and other conditions that affect the lower extremities can be identified with careful history and physical examination, confirmed with limited testing, and can be treated successfully. Distal symmetric polyneuropathy is the most common lower extremity disorder, but it must be distinguished from similar-appearing neuropathies caused by medications, B12 deficiency, or vasculitis. Diffuse infiltrative lymphocytosis syndrome also causes a painful peripheral neuropathy that must be distinguished from distal symmetric polyneuropathy. Inflammatory demyelinating polyneuropathies are characterized by muscle weakness. They occur in early, asymptomatic HIV infection and respond to plasmapheresis or steroids. Mononeuropathies in patients with CD4 counts more than 200 often resolve on their own. Multiple mononeuropathies, which occur in patients with CD4 counts less than 50, are often associated with cytomegalovirus infection and may follow a rapidly progressive course unless treated promptly and aggressively. Progressive polyradiculopathy occurs late in the course of AIDS, is often caused by cytomegalovirus, is rapidly progressive, and generally is fatal unless recognized and treated promptly. Muscle weakness, myalgia, and fatigue are common in HIV and have multiple causes. Lower extremity spasticity may be caused by treatable etiologies such as spinal cord abscess, tumor, disc compression, B12 deficiency, or ischemia. Gait disturbances are common but nonspecific and may be caused by treatable neurologic disorders at any level of the neuraxis.
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PMID:Neurologic problems of the lower extremity associated with HIV and AIDS. 957 54

We report 10 HTLV-I virus seropositive subjects, eight of them with HTLV-I associated myelopathy (HAM), two of them also infected with HIV as well as two asymptomatic HTLV-I+ relatives of two unrelated patients. HTLV-I is endemic in several tropical areas, where it causes different neurological diseases. Only few patients have been reported in our country since 1994. We studied 8 patients, who fulfilled the clinical criteria for chronic spastic paraplegia, and 2 other non-symptomatic HTLV-I seropositive relatives, with electromyography (EMG), motor and sensory conduction velocities (NCV), somatosensory, visual and brainstem auditory evoked potentials (SSEP, VEP and BAEP), Magnetic Resonance Images (MRI) and cerobrospinal fluid (CSF) analysis. The latter was carried out only in seven symptomatic patients. In every case positive ELISA tests for HTLV-I/II were confirmed by Western Blot. The two asymptomatic persons were clinically and electromyographically assessed, one of them was also submitted to SSEPs studies. Three patients were males. Patient's ages ranged from 5 to 65 years old. All symptomatic patients showed muscular weakness, spasticity with pyramidal signs and sphincter disturbances. Five of them had paresthesias and 2 had burning pain on their feet. The EMGs and the NCVs were normal in 7 patients and in the 2 asymptomatic ones. SSEPs, obtained by stimulating the posterior tibial nerves, were impaired in 7 patients and in the asymptomatic person who received the procedure. The 7 symptomatic patients who underwent lumbar puncture had positive tests for HTLV-I in CSF, 3 out of these 7 patients had also high protein levels and 4 had increased number of lymphocytes. In 2 patients intrathecal IgG production could also be demonstrated. MRI were normal in 7 patients and in the 2 asymptomatics, the exception being a female who had bilateral hyperintense lesions in cerebral white matter in T2. In conclusion, tropical spastic paraparesis is apparently a rare disorder in Argentina. However, some cases have been reported recently. Most probably, its prevalence is currently underestimated. Its diagnosis should be considered in every patient with progressive spastic paraplegia.
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PMID:Further studies on HTLV-I associated myelopathy in Argentina. 981 4

The plant Cannabis sativa has a long history of medical use in the treatment of pain and spasms, the promotion of sleep, and the suppression of nausea and vomiting. However, in the early 70s cannabis was classified in the Narcotic Acts in countries all over the world as having no therapeutic benefit; therefore, it cannot be prescribed by physicians or dispensed by pharmacists. In the light of this contradictory situation an increasing number of patients practices a self-prescription with cannabis products for relieving a variety of symptoms. An anonymous standardized survey of the medical use of cannabis and cannabis products of patients in Germany, Austria and Switzerland was conducted by the Association for Cannabis as Medicine (Cologne, Germany). During about one year 170 subjects participated in this survey; questionnaires of 128 patients could be included into the evaluation. 68% of these participants were males, 32% females, with a total mean age of 37.5 (+/- 9.6) years. The most frequently mentioned indications for medicinal cannabis use were depression (12.0%), multiple sclerosis (10.8%), HIV-infection (9.0%), migraine (6.6%), asthma (6.0%), back pain (5.4%), hepatitis C (4. 8%), sleeping disorders (4.8%), epilepsy (3.6%), spasticity (3.6%), headache (3.6%), alcoholism (3.0%), glaucoma (3.0%), nausea (3.0%), disk prolapse (2.4%), and spinal cord injury (2.4%). The majority of patients used natural cannabis products such as marihuana, hashish and an alcoholic tincture; in just 5 cases dronabinol (Marinol) was taken by prescription. About half of the 128 participants of the survey (52.4%) had used cannabis as a recreational drug before the onset of their illness. To date 14.3% took cannabis orally, 49.2% by inhalation and in 36.5% of cases both application modes were used. 72.2% of the patients stated the symptoms of their illness to have 'much improved' after cannabis ingestion, 23.4% stated to have 'slightly improved', 4.8% experienced 'no change' and 1.6% described that their symptoms got 'worse'. Being asked for the satisfaction with their therapeutic use of cannabis 60.8% stated to be 'very satisfied', 24.0% 'satisfied', 11.2% 'partly satisfied' and 4.0% were 'not satisfied'. 70.8% experienced no side effects, 26.4% described 'moderate' and 3.3% 'strong' side effects. 84.1% of patients have not felt any need for dose escalation during the last 3 months, 11.0% had to increase their cannabis dose 'moderately' and 4.8% 'strongly' in order to maintain the therapeutic effects. Thus, this survey demonstrates a successful use of cannabis products for the treatment of a multitude of various illnesses and symptoms. This use was usually accompanied only by slight and in general acceptable side effects. Because the patient group responding to this survey is presumably highly selected, no conclusions can be drawn about the quantity of wanted and unwanted effects of the medicinal use of the hemp plant for particular indications.
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PMID:[Results of a standardized survey on the medical use of cannabis products in the German-speaking area]. 2146 33

HIV-related encephalopathy is an important problem in vertically infected children with HIV. Infected infants may manifest early, catastrophic encephalopathy, with loss of brain growth, motor abnormalities, and cognitive dysfunction. Even without evidence of AIDS, infected infants score lower than serorevertors on developmental measures, particularly language acquisition. Children with perinatal or later transfusion-related infection generally are roughly comparable developmentally to their peers until late in their course. Symptoms similar to adult AIDS dementia complex are occasionally seen in adolescents with advanced AIDS, including dementia, bradykinesia, and spasticity. Opportunistic CNS infections such as toxoplasmosis and progressive multifocal leukoencephalopathy are less common in children and adolescents than in adults. Increasing evidence suggests that aggressive antiretroviral treatment may halt or even reverse encephalopathy. Neuroimaging changes may precede or follow clinical manifestations, and include early lenticulostriate vessel echogenicity on cranial ultrasound, calcifying microangiopathy on CT scan, and/or white matter lesions and central atrophy on MRI. Differential diagnosis of neurological dysfunction in an HIV-infected infant includes the effects of maternal substance abuse, other CNS congenital infections, and other causes of early static encephalopathy. Initial entry of HIV into the nervous system occurs very early in infection. The risk of clinical HIV encephalopathy increases with very early age of infection and with high viral loads. Virus is found in microglia and brain derived macrophages, not neurons. The neuronal effect of HIV is probably indirect, with various cytokines implicated. Apoptosis is the presumed mechanism of damage to neurons by HIV.
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PMID:Neurological and developmental effects of HIV and AIDS in children and adolescents. 1155 37

Considerable progress has been made in understanding and treating pain associated with pediatric AIDS. The World Health Organization (WHO) estimates that 1000 new pediatric HIV infections occur daily, with 67% in Africa and 30% in South and Southeast Asia. Perinatally infected children show two types of progression, a precocious form that is usually fatal by the 4th year and a less rapidly progressing form in which survival exceeds 80% at age 7. Neurologic effects are frequently apparent by 3-6 months in the severe form. The pain may result specifically from the HIV infection and its complications, from intercurrent or opportunistic infections, or from examinations and treatment. The emotional pain suffered by pediatric HIV patients is often very great. Seropositive children are more subject to bacterial infections than seropositive adults, and their infections are more recurrent, prolonged, and painful than those in immunocompetent children. Infants with HIV encephalopathy may suffer painful sensations from mild stimuli and extreme irritability and spasticity. Abdominal HIV pain often results from multifactorial etiologies, and the usual therapies may be of little efficacy. Children with full-blown AIDS may complain of joint or muscle pain or headaches that are of unexplained etiology. Indications for painful diagnostic procedures should be carefully considered before the child is subjected to them, and protocols for analgesia should be developed. Pain medications may be selected according to the WHO classification, in accordance with the intensity of the pain. Antidepressants and anticonvulsants may be used for neuropathic pain, and painful spasticity may be reduced with myorelaxants. Children are often responsive to behavioral methods such as relaxation, hypnosis, or distraction.
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PMID:[Pain from AIDS (child)]. 1234 7

The major psychoactive constituent of Cannabis sativa, delta(9)-tetrahydrocannabinol (delta(9)-THC), and endogenous cannabinoid ligands, such as anandamide, signal through G-protein-coupled cannabinoid receptors localised to regions of the brain associated with important neurological processes. Signalling is mostly inhibitory and suggests a role for cannabinoids as therapeutic agents in CNS disease where inhibition of neurotransmitter release would be beneficial. Anecdotal evidence suggests that patients with disorders such as multiple sclerosis smoke cannabis to relieve disease-related symptoms. Cannabinoids can alleviate tremor and spasticity in animal models of multiple sclerosis, and clinical trials of the use of these compounds for these symptoms are in progress. The cannabinoid nabilone is currently licensed for use as an antiemetic agent in chemotherapy-induced emesis. Evidence suggests that cannabinoids may prove useful in Parkinson's disease by inhibiting the excitotoxic neurotransmitter glutamate and counteracting oxidative damage to dopaminergic neurons. The inhibitory effect of cannabinoids on reactive oxygen species, glutamate and tumour necrosis factor suggests that they may be potent neuroprotective agents. Dexanabinol (HU-211), a synthetic cannabinoid, is currently being assessed in clinical trials for traumatic brain injury and stroke. Animal models of mechanical, thermal and noxious pain suggest that cannabinoids may be effective analgesics. Indeed, in clinical trials of postoperative and cancer pain and pain associated with spinal cord injury, cannabinoids have proven more effective than placebo but may be less effective than existing therapies. Dronabinol, a commercially available form of delta(9)-THC, has been used successfully for increasing appetite in patients with HIV wasting disease, and cannabinoid receptor antagonists may reduce obesity. Acute adverse effects following cannabis usage include sedation and anxiety. These effects are usually transient and may be less severe than those that occur with existing therapeutic agents. The use of nonpsychoactive cannabinoids such as cannabidiol and dexanabinol may allow the dissociation of unwanted psychoactive effects from potential therapeutic benefits. The existence of other cannabinoid receptors may provide novel therapeutic targets that are independent of CB(1) receptors (at which most currently available cannabinoids act) and the development of compounds that are not associated with CB(1) receptor-mediated adverse effects. Further understanding of the most appropriate route of delivery and the pharmacokinetics of agents that act via the endocannabinoid system may also reduce adverse effects and increase the efficacy of cannabinoid treatment. This review highlights recent advances in understanding of the endocannabinoid system and indicates CNS disorders that may benefit from the therapeutic effects of cannabinoid treatment. Where applicable, reference is made to ongoing clinical trials of cannabinoids to alleviate symptoms of these disorders.
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PMID:Therapeutic potential of cannabinoids in CNS disease. 1261 97

We report a 47-year-old woman with progressive multifocal leukoencephalopathy (PML). She was a carrier of HTLV-I virus, and developed subacute right hemiparesis and marked motor aphasia. She had a malignant lymphoma in the left neck and basal cell carcinoma in the right inguinal region. Three months after the onset, she became unable to walk because of the right leg weakness or to speak because of motor aphasia. Magnetic resonance imaging (MRI) revealed multifocal T2-high lesions in the white matter of the left frontal lobe, and a brain biopsy revealed demyelinating pathology. A biopsy of the left parotid gland revealed a diffuse pleomorphic type large B cell lymphoma. Although anti-HTLV-I antibody was positive in the serum and cerebrospinal fluid (CSF), no adult T-cell leukemia (ATL) cells were found in the blood or CSF. The patient was then admitted to our hospital. Neurological examinations revealed severe motor aphasia, mild sensory aphasia/cognitive impairment, right hemiplegia, mild right hemihypesthesia, limb-kinetic apraxia in the left hand, idiomotor apraxia, agraphia, perseveration, marked spasticity and brisk tendon reflex in four extremities, and positive bilateral pathological reflexes. MRI showed multifocal T2-high lesions mainly in the cerebral white matter, predominantly in the left hemisphere, and partly in the cerebral cortex. No gadolinium enhancement was found. In addition, 99mTcECD-SPECT showed a broad decrease in cerebral blood flow (CBF) in the cortex. Anti-HTLV-I antibody was positive but anti-HIV antibody was negative in serum. ATL cells were found in 1-3% of the peripheral white blood cells after admission. CSF examination revealed that the cell count (1/microl), protein level (24 mg/dl), and IgG index (0.4) were all normal. However, the myelin basic protein level (321 pg/ml; normal < 102) was increased, JC virus DNA was detected by PCR, and anti-HTLV-I antibody (x 8) was detected in CSF. The regulatory region of the JC virus DNA in the CSF was partly deleted; immunostaining with anti-JC virus protein antibodies revealed the existence of JC virus in biopsied brain specimens, and these findings were consistent with PML. Her symptoms such as motor aphasia, cognitive dysfunction and left hemiparesis were subacutely progressive, and she developed akinetic mutism two weeks after admission. Since the efficacy of cytosine arabinoside for PML has been reported, she was administered 80 mg/day of the drug for five days. After treatment, her communication function was mildly improved but the efficacy was transient. Since it has been reported that HTLV-I, as well as HIV, activates the JC virus promoter and its proliferation, the latent infection of HTLV-I in the central nervous system (CNS) in this case might have stimulated the JC virus proliferation, promoting lesion extension over the cerebral cortex. There have been only a few reports of broad decreases in CBF by SPECT in PML patients. Further MRI and SPECT studies on PML patients are therefore necessary to evaluate the significance of HTLV-I in promoting the JC virus infiltration into the CNS.
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PMID:[A case of progressive multifocal leukoencephalopathy presenting white matter MRI lesions extending over the cerebral cortex and a marked decrease in cerebral blood flow on SPECT, and associated with HTLV-I infection]. 1602 67

With better understanding of the pathogenesis of AIDS and the advent of anti-retroviral medications, patients with HIV are living longer and the probability that they will suffer musculoskeletal complications are increasing. There is a vast array of musculoskeletal impairments including rheumatologic, infectious, and non-infectious conditions. We report a 53-year-old man with longstanding shoulder pain, weakness, and spasticity of the upper extremity which was diagnosed as adhesive capsulitis secondary to brain abscess. Musculoskeletal problems may be complicated with neurological involvement as in our case and patients should be investigated for possible underlying life-threatening disease.
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PMID:HIV infection and shoulder pain: a challenging case. 1613 80


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