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)

The nucleoside analog 2',3'-dideoxycytidine (ddC) is a potent inhibitor of the reverse transcriptase of human immunodeficiency virus and a DNA chain terminator. In clinical trials in patients with acquired immunodeficiency syndrome, ddC treatment has been associated with a dose-limiting and dose-dependent, painful, sensorimotor peripheral neuropathy. In search of an animal model for ddC-induced neurotoxicity we studied 36 New Zealand White rabbits (3 males/3 females/group) given 0, 10, 50, 100, 150, or 250 mg/kg/day of ddC, by oral intubation, for 13 or 18 weeks. Rabbits in the 150 and 250 mg/kg/day groups were sacrificed at 13 weeks because of hematopoietic toxicity. After 16 weeks, rabbits in the 50 and 100 mg/kg/day groups showed hindlimb paresis and/or gait abnormalities. Nerve conduction velocities and amplitudes in the 100 mg/kg/day rabbits were reduced by 30 to 50%. The most prominent pathologic changes in peripheral nerve and ventral roots of ddC-treated rabbits were (a) myelin splitting and intramyelinic edema, (b) demyelination and remyelination of axons, and (c) axonal loss. Treatment-related histologic lesions were not observed in spinal cord, brain, or retina. The pathology in these ddC-treated rabbits is consistent with a peripheral myelinopathy and axonopathy. This represents the first clinical, electrophysiologic, and pathologic description of an animal model of a peripheral neuropathy induced by a nucleoside analog.
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PMID:Peripheral neuropathy induced by 2',3'-dideoxycytidine. A rabbit model of 2',3'-dideoxycytidine neurotoxicity. 130 30

Peripheral nerve lesions observed in the progressive immunodeficiency associated with infection are remarkable for their diversity and their potential severity. At the onset, demyelinating neuropathies predominate, often with signs of atypical polyradiculoneuritis associated with inflammatory lesions or vasculitis sometimes of the necrotizing type, as that observed in periarteritis nodosa. Later on, at the immunosuppression stage, axonal lesions predominate. At the AIDS stage one may find lymphomatous infiltration of nerves and nerve roots and, chiefly, opportunistic cytomegalovirus (CMV) infection. This infection produces meningoradiculitis, mainly in the territory of the cauda equina, or multifocal neuropathy frequently associated with CMV retinitis. Early treatment of CMV neuropathies may stabilize the lesions or even result in functional improvement, but the overall prognosis of late neuropathies remains poor.
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PMID:[Peripheral neurologic manifestations of infection by the human immunodeficiency virus]. 131 15

A peripheral nerve biopsy was performed in 15 patients with human immunodeficiency virus (HIV) infection and polyneuropathy. Two cases [1 asymptomatic, 1 AIDS-related complex (ARC)] presented with chronic inflammatory demyelinating polyneuropathy; there was 1 case (asymptomatic) of mononeuropathy multiplex and 12 cases (1 asymptomatic, 1 ARC, 10 AIDS) with distal symmetrical polyneuropathy. Epi- or endoneurial microvasculitis was observed in 6 cases. Electron microscopy showed that nerve fiber lesions were mainly axonal. Severe segmental demyelination was also present in both cases of chronic inflammatory demyelinating polyneuropathy, with characteristic features of active demyelination in one. Numerous plasmacytoid cells were found in the endoneurium in 4 patients. Tubuloreticular inclusions were present in endothelial cells in the 10 cases with AIDS but absent in the other patients. Direct immunopathological examination with anti-immunoglobulin sera was negative in all cases. HIV was evidenced by in situ hybridization in 2 AIDS patients; no Epstein-Barr virus or cytomegalovirus was detected.
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PMID:Morphological findings on peripheral nerve biopsies in 15 patients with human immunodeficiency virus infection. 132 1

We describe two cases of serologically confirmed human T-lymphotropic virus type I (HTLV-I)-associated myelopathy involving North American men coinfected by the human immunodeficiency virus type 1. Our first patient suffered from a gradually progressive spastic paraparesis for 10 years prior to presenting with Kaposi's sarcoma, while our second patient developed subacutely progressive spastic paraparesis in the setting of full-blown acquired immunodeficiency syndrome. Autopsy examination of the spinal cords from these two cases revealed widespread axonal loss and demyelination principally involving the lateral columns of case no. 1 and the lateral and anterior columns of case no. 2. Vascular sclerosis and hyalinization were prominent in both cases, but in neither was there a conspicuous inflammatory component. In case no. 2, HTLV-I mRNA was not detected by in situ hybridization, but HTLV-I proviral DNA sequences were detected in this case by polymerase chain reaction. Neither case exhibited multinucleated cell (human immunodeficiency virus type 1) myelitis, vacuolar myelopathy, or evidence of HTLV-II infection by polymerase chain reaction assay.
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PMID:Human T-lymphotropic virus type I-associated myelopathy in patients with the acquired immunodeficiency syndrome. 156 47

We compared the sural nerves from patients with AIDS; four with the painful peripheral neuropathy (PPN), three patients with non-painful distal symmetrical peripheral neuropathy (DSPN), one without clinical peripheral nerve involvement and two human immunodeficiency virus negative controls. Fibre diameter distributions showed a slight reduction in larger fibres in all patients with AIDS compared with controls. No significant difference was found in the relative frequency distribution of the lamellae counts between any of the groups. The relative frequency distribution of axonal area of myelinated fibres did not differ between controls, non-painful DSPN or the patient without peripheral nerve involvement; however, all patients with PPN showed marked reduction in the number of axons of myelinated fibres of larger area which was significant when compared to each patient from the other groups (P less than 0.0001). This indicates that the reduction in larger fibres in PPN is mostly due to axonal atrophy rather than selective fibre loss. Axonal atrophy is associated with painful peripheral neuropathy in AIDS but not with those without pain. The possible role of axonal atrophy as a pathological substrate for pain is discussed.
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PMID:Axonal atrophy in the painful peripheral neuropathy in AIDS. 196 27

We describe a 34-year-old man from southern Florida with a history of intravenous drug use, dually infected with human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus type II (HTLV-II), who developed a myelopathy clinically indistinguishable from HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). This myelopathy was characterized by spastic lower extremity weakness, distal paresthesias, sensory loss with a discrete thoracic level to pinprick, back pain, impotence, and sphincter disturbances. Nerve conduction studies revealed an associated mixed axonal and demyelinative neuropathy. Despite a lack of response to 10 months of zidovudine therapy, the myeloneuropathy improved dramatically 2 years after its onset in the absence of any therapeutic intervention.
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PMID:Tropical spastic paraparesis-like illness occurring in a patient dually infected with HIV-1 and HTLV-II. 198

We report five patients with human immunodeficiency virus (HIV) infection in stages IV-C1, IV-C2 and IV-D who developed peripheral polyneuropathy (PNP). Two patients had invalidating PNP with a demyelinating predominance, while in the remaining three axonal component predominated. However, both components were present in different degrees in all patients. We have observed two cases with transition from one type of PNP to the other during the course of the disease. Inflammatory polyradiculoneuropathy usually develops in the initial stages of the infection, while the distal axonal type is more commonly seen in patients with advanced infection. The possibility that PNP could have, in these patients, a common etiology and pathogenesis with variable clinical and electrophysiological expression is discussed.
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PMID:[Polyneuropathy associated with human immunodeficiency virus infection]. 215 3

Symptomatic polyneuropathy in human immunodeficiency virus (HIV) infection was studied in ten men with acquired immunodeficiency syndrome (AIDS) and in ten men without the immune deficiency. In both groups of patients electrophysiological signs of polyneuropathy of the axonal type were present in the sural, median and peroneal nerves. The AIDS patients had a greater reduction of the mean (SD) sural nerve action potential, 3.1 (2.7) microV, than in patients without AIDS, 10.2 (6.1) microV (p less than 0.01) and greater slowing of peroneal nerve conduction velocity, 42.6 (1.4) m/s in AIDS patients versus 52.6 (3.3) m/s in patients without AIDS (p less than 0.0001). These findings indicate that in most HIV infected patients the severity but not the type of neuropathy depends on whether an immune deficient state has developed. Seven patients with symptomatic polyneuropathy were treated with azidothymidine (AZT) for an average of 10 months and compared with a group of five untreated patients with similar symptoms. No effect of AZT treatment on sural or median nerve amplitude or conduction velocity or on the vibratory or temperature thresholds was observed.
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PMID:Symptomatic polyneuropathy in human immunodeficiency virus antibody seropositive men with and without immune deficiency: a comparative electrophysiological study. 229 97

Neuromuscular diseases are common in acquired immune deficiency syndrome (AIDS). Although the clinical incidence of peripheral neuropathy has not been systematically studied, various reports suggest that up to 40% of AIDS patients have clinical symptoms. Biopsy and autopsy studies have shown an inflammatory neuropathy with a variable component of demyelination and axonal loss. Evidence of direct involvement by the human immunodeficiency virus (HIV) is scant. Immunosuppression followed by cytomegalovirus (CMV) infection appears to be a direct cause of polyradiculoneuropathy and perhaps other forms of peripheral neuropathy in AIDS. The clinical incidence of myopathy in AIDS is less clear, and clinically less appreciated than the neuropathy. Scattered reports have identified an inflammatory myopathy that does not appear to be due to direct HIV infection, but could be mediated by another human retrovirus. HIV seropositive patients being treated with antiviral drugs develop a unique set of neuromuscular diseases that must be distinguished from the non-drug-related conditions.
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PMID:Neuromuscular diseases of AIDS. 255 21

Twenty five patients with peripheral neuropathy at different stages of human immunodeficiency virus (HIV) infection are reported. Cerebrospinal fluid (CSF) findings were available in 17 cases, electrophysiology in all and a neuromuscular biopsy in 11. Of six otherwise asymptomatic HIV+ patients, five had chronic inflammatory demyelinating polyneuropathy (CIDP) and one acute inflammatory demyelinating polyneuropathy (AIDP). CSF showed pleocytosis in all cases. Infiltration of the endoneurium and/or the epineurium by mononuclear cells was seen in biopsies from three cases. These six patients recovered either spontaneously, or with corticosteroids or plasmaphereses. Of five patients with AIDS related complex (ARC), three had distal predominantly sensory peripheral neuropathy (DSPN), one CIDP and one mixed neuropathy. Of 14 patients with AIDS, one had mononeuropathy multiplex and 13 painful DSPN. Electrophysiological studies were consistent with an axonopathy. Nerve biopsies in six cases showed axonal changes but surprisingly associated with marked segmental demyelination in two cases. Cell infiltration was present in nerve samples in two cases. Five patients died within six months after the onset of the neuropathy.
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PMID:The spectrum of polyneuropathies in patients infected with HIV. 255 61


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