Spectrum of opportunistic infections and malignancies in patients with human immunodeficiency virus infection in South Korea.
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To determine the frequency and types of major opportunistic diseases in patients with HIV infection in South Korea, we reviewed the medical records of 173 HIV-infected patients. The patients were seen from 1985 to 1998 at a referral hospital for AIDS in South Korea. Most patients (85%) were male, and 107 (62%) were infected by heterosexual contacts. CD4+ lymphocyte counts at presentation were <200/microL in 27% of the patients. Tuberculosis was the most frequent opportunistic infection (25% of patients), followed by candidiasis (21%), herpes zoster (20%), Pneumocystis carinii pneumonia (10%), cytomegalovirus disease (9.8%). There were no cases of toxoplasmosis. Kaposi's sarcoma developed in 3 patients (1.7%), and non-Hodgkin's lymphoma, in 2 (1.2%). Eleven patients (6.4%) developed peripheral neuropathy, and 8 (4.6%) had HIV encephalopathy. Tuberculosis was the single most important HIV-related infection in South Korean patients. (+info)
Neuropathy target esterase.
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Neuropathy target esterase (NTE) is an integral membrane protein present in all neurons and in some non-neural-cell types of vertebrates. Recent data indicate that NTE is involved in a cell-signalling pathway controlling interactions between neurons and accessory glial cells in the developing nervous system. NTE has serine esterase activity and efficiently catalyses the hydrolysis of phenyl valerate (PV) in vitro, but its physiological substrate is unknown. By sequence analysis NTE has been found to be related neither to the major serine esterase family, which includes acetylcholinesterase, nor to any other known serine hydrolases. NTE comprises at least two functional domains: an N-terminal putative regulatory domain and a C-terminal effector domain which contains the esterase activity and is, in part, conserved in proteins found in bacteria, yeast, nematodes and insects. NTE's effector domain contains three predicted transmembrane segments, and the active-site serine residue lies at the centre of one of these segments. The isolated recombinant domain shows PV hydrolase activity only when incorporated into phospholipid liposomes. NTE's esterase activity appears to be largely redundant in adult vertebrates, but organophosphates which react with NTE in vivo initiate unknown events which lead, after a delay of 1-3 weeks, to a neuropathy with degeneration of long axons. These neuropathic organophosphates leave a negatively charged group covalently attached to the active-site serine residue, and it is suggested that this may cause a toxic gain of function in NTE. (+info)
Neuroactive neurosteroids as endogenous effectors for the sigma1 (sigma1) receptor: pharmacological evidence and therapeutic opportunities.
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Neuroactive neurosteroids, including progesterone, allopregnanolone, pregnenolone and dehydroepiandrosterone, represent steroid hormones synthesized de novo in the brain and acting locally on nervous cells. Neurosteroids modulate several neurotransmitter systems such as gamma-aminobutyric acid type A (GABA(A)), N-methyl-D-aspartate (NMDA) and acetylcholine receptors. As physiologic consequences, they are involved in neuronal plasticity, learning and memory processes, aggression and epilepsy, and they modulate the responses to stress, anxiety and depression. The sigma1-receptor protein was recently purified and its cDNA was cloned in several species. The amino-acid sequences are structurally unrelated to known mammalian proteins, but shared homology with a fungal sterol C8-C7 isomerase. The sigma1-receptor ligands exert a potent neuromodulation on excitatory neurotransmitter systems, including the glutamate and cholinergic systems. Consequently, selective sigma1 agonists show neuroprotective properties and beneficial effects in memory processes, stress and depression. The evidence of a direct interaction between neurosteroids and sigma1 receptors was first suggested by the ability of several steroids to inhibit the binding of sigma1-receptor radioligands in vitro and in vivo. A crossed pharmacology between neurosteroids and sigma1-receptor ligands was described in several physiological tests and behavioral responses. This review will detail the recent evidence for a common mechanism of action between neurosteroids and sigma1-receptor ligands and focus on the potential therapeutic interests of such interaction in the physiopathology of learning and memory impairments, stress, depression and neuroprotection. (+info)
Increased incidence of neurological complications in patients receiving an allogenic bone marrow transplantation from alternative donors.
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OBJECTIVE: To compare the frequency and type of neurological complications after bone marrow transplantation (BMT) with an HLA identical unrelated donor or a mismatched related donor (alternative donors) to the neurological complications after matched sibling BMT for standard and high risk leukaemia or myelodysplastic syndromes. METHODS: Retrospective analysis of consecutively treated patients with (a) BMT from alternative donors (n=39), (b) treated with matched sibling BMT for standard risk leukaemia, myelodysplastic syndromes, or aplastic anaemia (n=53), and (c) treated with matched sibling BMT for high risk leukaemia, myelodysplastic syndromes, or aplastic anaemia (n=49). RESULTS: A total of 72 neurological complications were found. Most of these occurred within the first 6 months after transplant. Thirty six patients developed a severe neurological complication: 17 Alternative donor patients (44%) by contrast with six standard risk patients (11%) and 13 high risk patients (27%; p<0.005). The most frequent complication was a metabolic encephalopathy occurring in 18% of patients. Most of the encephalopathies were caused by either the transplant procedure, cyclosporin, systemic infections, microangiopathic thrombopathy, or by complications induced by graft versus host disease. Infections of the CNS developed in 9% of patients, cerebrovascular lesions in 3%. CONCLUSIONS: Severe neurological complications are more frequent after BMT from alternative donors. This is mainly due to increased treatment related morbidity and to more profound immunosuppression after BMT from alternative donors. (+info)
HIV antibody profiles in serum and CSF of patients with neurological disease can serve as predictors of outcome.
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The serum and CSF antibody profiles were investigated in 100 patients with HIV in relation to the type and severity of neurological disease. Among them, 87 were positive for anti-HIV antibodies in the CSF. In 30 of 87 patients detailed analysis by western blot could be performed. In 20 of 30 the profiles were dissimilar, with more of bands being found in the serum than in the CSF. The correlation of western blot profiles to the clinical outcome indicated that the number of anti-HIV antibody bands as well as the index in the CSF of fatal cases were significantly less compared with non-fatal cases (p=0.019 and p=0.039 respectively). (+info)
Thalamocortical dysrhythmia: A neurological and neuropsychiatric syndrome characterized by magnetoencephalography.
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Spontaneous magnetoencephalographic activity was recorded in awake, healthy human controls and in patients suffering from neurogenic pain, tinnitus, Parkinson's disease, or depression. Compared with controls, patients showed increased low-frequency theta rhythmicity, in conjunction with a widespread and marked increase of coherence among high- and low-frequency oscillations. These data indicate the presence of a thalamocortical dysrhythmia, which we propose is responsible for all the above mentioned conditions. This coherent theta activity, the result of a resonant interaction between thalamus and cortex, is due to the generation of low-threshold calcium spike bursts by thalamic cells. The presence of these bursts is directly related to thalamic cell hyperpolarization, brought about by either excess inhibition or disfacilitation. The emergence of positive clinical symptoms is viewed as resulting from ectopic gamma-band activation, which we refer to as the "edge effect." This effect is observable as increased coherence between low- and high-frequency oscillations, probably resulting from inhibitory asymmetry between high- and low-frequency thalamocortical modules at the cortical level. (+info)
Ablation of P/Q-type Ca(2+) channel currents, altered synaptic transmission, and progressive ataxia in mice lacking the alpha(1A)-subunit.
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The Ca(2+) channel alpha(1A)-subunit is a voltage-gated, pore-forming membrane protein positioned at the intersection of two important lines of research: one exploring the diversity of Ca(2+) channels and their physiological roles, and the other pursuing mechanisms of ataxia, dystonia, epilepsy, and migraine. alpha(1A)-Subunits are thought to support both P- and Q-type Ca(2+) channel currents, but the most direct test, a null mutant, has not been described, nor is it known which changes in neurotransmission might arise from elimination of the predominant Ca(2+) delivery system at excitatory nerve terminals. We generated alpha(1A)-deficient mice (alpha(1A)(-/-)) and found that they developed a rapidly progressive neurological deficit with specific characteristics of ataxia and dystonia before dying approximately 3-4 weeks after birth. P-type currents in Purkinje neurons and P- and Q-type currents in cerebellar granule cells were eliminated completely whereas other Ca(2+) channel types, including those involved in triggering transmitter release, also underwent concomitant changes in density. Synaptic transmission in alpha(1A)(-/-) hippocampal slices persisted despite the lack of P/Q-type channels but showed enhanced reliance on N-type and R-type Ca(2+) entry. The alpha(1A)(-/-) mice provide a starting point for unraveling neuropathological mechanisms of human diseases generated by mutations in alpha(1A). (+info)
Phase I study of dose-escalated paclitaxel, ifosfamide, and cisplatin (PIC) combination chemotherapy in advanced solid tumours.
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Based on the already known in vitro synergy between paclitaxel (taxol), cisplatin and oxazophosphorine cytostatics and the broad spectrum of activity of the above drugs we sought to evaluate the paclitaxel (taxol)-ifosfamide-cisplatin (PIC) combination in the outpatient setting in individuals with a variety of advanced solid tumours. Cohorts of patients were entered into six successive dose levels (DLs) with drug doses ranging as follows: paclitaxel 135-215 mg m(-2) day 1 - (1 h infusion), ifosfamide 4.5-6.0 g m(-2) (total dose) - divided over days 1 and 2, and cisplatin 80-100 mg m(-2) (total) - divided over days 1 and 2. Granulocyte colony-stimulating factor was given from day 5 to 14. Forty-two patients were entered. Eighteen patients had 2-8 cycles of prior chemotherapy with no taxanes or ifosfamide (cisplatin was allowed). The regimen was tolerated with outpatient administration in 36/42 patients. Toxicities included: grade 4 neutropenia for < or = 5 days in 27% of cycles; 5 episodes of febrile neutropenia in three patients at DL-III, -V and -VI. Grade 3/4 thrombocytopenia and cumulative grade 3 anaemia were seen in 7% and 13% of cycles respectively. Three cases of severe grade 3 neuromotor/sensory neuropathy were recorded at DL-II, -III, and -V, all after cycle 3. The maximum tolerated dose was not formally reached at DL-V, but because of progressive anaemia and asthenia/fatigue, it was decided to test a new DL-VI with doses of paclitaxel 200 mg m(-2), ifosfamide 5.0 g m(-2) and cisplatin 100 mg m(-2); this appeared to be tolerable and is recommended for further phase II testing. The response rate was 47.5% (complete response + partial response: 20/42). The PIC regimen appears to be feasible and safe in the outpatient setting. Care should be paid to neurotoxicity. Phase II studies are starting in non-small-cell lung cancer, ovarian cancer and head and neck cancer at DL-VI. (+info)