Spiking neurons, receiving temporally encoded inputs, can compute radial basis functions (RBFs) by storing the relevant information in their delays. In this paper we show how these delays can be learned using exclusively locally available information (basically the time difference between the pre- and postsynaptic spikes). Our approach gives rise to a biologically plausible algorithm for finding clusters in a high-dimensional input space with networks of spiking neurons, even if the environment is changing dynamically. Furthermore, we show that our learning mechanism makes it possible that such RBF neurons can perform some kind of feature extraction where they recognize that only certain input coordinates carry relevant information. Finally we demonstrate that this model allows the recognition of temporal sequences even if they are distorted in various ways.

Action Potentials↗

PubMed1997

Selective expansion of gammadelta T cells among liver-derived lymphocytes of AIDS patients with disseminated Mycobacterium avium complex infection.

The aim of this study was to investigate a potential expansion of gammadelta T cells in AIDS patients in response to disseminated infection with Mycobacterium avium complex. Liver-derived lymphocytes and peripheral blood lymphocytes were obtained from 5 AIDS patients with disseminated Mycobacterium avium complex infection and 10 HIV-infected patients without mycobacterial disease. Control patients included 14 HIV-negative patients without bacterial disease and 4 HIV-negative patients with disseminated Mycobacterium tuberculosis infection. The percentage of gammadelta T cells among CD3+ T lymphocytes was determined by flow cytometry. gammadelta T cells were markedly enhanced in liver biopsies but not among peripheral blood lymphocytes of AIDS patients with disseminated M. avium complex infection (median liver gammadelta/CD3: 26%) as compared to HIV-infected control patients without mycobacterial disease (median liver gammadelta/CD3: 2.3%; P < 0,005). Disseminated infection with M. tuberculosis in HIV-negative patients leads to a similar expansion of gammadelta T cells among liver-derived CD3+ lymphocytes (median gammadelta/CD3: 15.5%) as compared to control patients without mycobacterial disease (median gammadelta/CD3: 2.15%; P < 0,001).

AIDS-Related Opportunistic Infections↗

PubMed1997

Enhanced expression of activation antigens HLA-DR and CD69 on gamma delta T cells but impaired interleukin-2-induced upregulation in HIV-1 infection.

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Acquired Immunodeficiency Syndrome↗

PubMed1996

Rifabutin versus placebo in combination with three drugs in the treatment of nontuberculous mycobacterial infection in patients with AIDS.

The aim of this double-blind, randomized, placebo-controlled, 12-week study was to assess the efficacy of rifabutin (450 or 600 mg/d) in the treatment of disseminated nontuberculous mycobacterial infection in patients with AIDS. Companion drugs in both arms of the study were ethambutol, clofazimine, and isoniazid. Because of low accrual, the study was prematurely terminated when a total of 382 patients had been enrolled, of which 200 were eligible (i.e., their specimens were culture-positive for Mycobacterium avium complex [MAC] or Mycobacterium xenopi at baseline) and 102 were evaluable (i.e., they were eligible, were treated for a minimum of 6 weeks, and had at least one culture assessment after baseline). The original protocol called for a total of 220 evaluable patients. At week 12, rifabutin treatment was associated with higher, although nonsignificant, rates of bacteriologic conversion than was the placebo arm, with regard to both the eligible patients (25% vs. 18%) and the evaluable patients (45% vs. 38%). Corresponding median times to culture conversion were 42 vs. 63 days (eligible patients) and 43 vs. 69 days (evaluable patients). No significant difference was observed in clinical improvement, mortality, or toxicity between the two treatment arms. The addition of rifabutin to a triple-drug regimen may contribute to the clearance of disseminated MAC infection in patients with AIDS, without causing additional toxicity.

AIDS-Related Opportunistic Infections↗

PubMed1996

Evidence for genetic regulation of susceptibility to toxoplasmic encephalitis in AIDS patients.

The frequency of HLA-DQ antigens in AIDS patients with toxoplasmic encephalitis (TE) were examined. HLA-DQ3 was significantly more frequent in white North American AIDS patients with TE (85.0%) than in the general white population (51.8%; P = .007, corrected P = .028) or randomly selected control AIDS patients who had not developed TE (40.0%; P = .016). In contrast, the frequency of HLA-DQ1 was lower in TE patients than in healthy controls (40.0% vs. 66.5%, P = .027), but this difference did not reach statistical significance when corrected for the number of variables tested (corrected P = .108 for the general white population). HLA-DQ3 thus appears to be a genetic marker of susceptibility to development of TE in AIDS patients, and DQ1 may be a resistance marker. These HLA associations with disease indicate that development of TE in AIDS patients is affected by a gene or genes in the HLA complex and that HLA-DQ typing may help in decisions regarding TE prophylaxis.

AIDS-Related Opportunistic Infections↗

PubMed1996

High-performance liquid chromatography determination of pyrimethamine, dapsone, monoacetyldapsone, sulfadoxine, and N-acetyl-sulfadoxine after rapid solid-phase extraction.

A solid-phase extraction procedure and a corresponding high-performance liquid chromatographic technique based on methods previously published by Edstein et al. (Edstein M. Quantification of antimalarial drugs. I. Simultaneous measurement of sulphadoxine, N4acetylsulphadoxine and pyrimethamine in human plasma. J Chromatogr 1984;305:502-7; Edstein M. Quantification of antimalarial drugs. II. Simultaneous measurement of dapsone, monoacetyldapsone and pyrimethamine in human plasma. J Chromatogr 1984;307:426-31) were developed for simultaneous determination of either dapsone (DDS), monoacetyldapsone (MADDS), and pyrimethamine (PYR) or sulfadoxine (SDX), N-acetyl-sulfadoxine (NAS) and pyrimethamine in plasma. Solid-phase extraction was achieved using C-18 extraction columns. An ionpair chromatography was performed on a C-18 analytical column (mu Bondapak C-18, 300 x 3.9 mm I.D.). Gradient elution with methanol, acetonitrile, PIC B6 reagent (1-hexanesulphonic acid), and water as mobile phase was applied. Ultraviolet detection was done at 210 nm for PYR, at 254 nm for SDX and NAS, and at 295 nm for DDS and MADDS. The extraction recoveries averaged 92.1% for PYR, 87.6% for DDS, 87.5% for MADDS, 91.2% for SDX, and 92.4% for NAS. The limit of quantification using 1.0-ml plasma samples was 15 ng/ml for PYR, DDS, MADDS, NAS, and 25 ng/ml for SDX (precision < 15%).

Anti-Infective Agents↗

PubMed1995

Isolation of atypical mycobacteria from tap water in hospitals and homes: is this a possible source of disseminated MAC infection in AIDS patients?

Infections caused by mycobacteria other than tuberculosis (MOTT), especially Mycobacterium avium complex (MAC), are common in AIDS patients, but rare in immunocompetent persons. The route of transmission is unknown, but tap water could provide a possible source of infection: MAC was isolated from tap water in the U.S.A. but this has not been reported in Germany. We therefore investigated tap water in Berlin for the presence of mycobacteria and compared radiometric (Bactec) and standard plate culture methods processing large volumes of water samples. The Bactec method yielded equal results compared to standard methods but had the advantage of easy handling. Mycobacteria were isolated from 50/118 (42.4%) samples and from 21/30 (70%) sites. The most frequently isolated species was Mycobacterium gordonae (from 28% samples and from 53.3% sites); MAC was isolated from two samples only (1.7%).

AIDS-Related Opportunistic Infections↗

PubMed1995

Intensive treatment of AIDS-related non-Hodgkin's lymphomas with the MACOP-B protocol.

The usefulness of intensive chemotherapy with the MACOP-B protocol was evaluated in 8 patients with AIDS-related non-Hodgkin's lymphoma (NHL). Four patients had a prior AIDS diagnosis. The median CD4+ lymphocyte count was 0.079 cells x 10(9)/l (range 0.016-0.330). All patients responded to treatment. Four patients finished chemotherapy, all with complete remission, while another 3 patients deteriorated prior to finishing treatment and died. The median survival was 4 months (range 1 to 86 months). Major causes of the poor outcome were AIDS-related opportunistic infections and meningeal CNS involvement by NHL developing during or after chemotherapy. Patients with AIDS-related NHL usually do not appear to benefit from treatment with MACOP-B protocol. Advanced immunodeficiency is associated with poor tolerance to treatment and inability to finish this chemotherapy protocol. MACOP-B chemotherapy does not prevent meningeal spread of lymphoma in spite of using repeatedly systemic methotrexate crossing the blood-brain barrier. CNS prophylaxis with repeated application of intrathecal methotrexate may lower the risk of meningeal spread of lymphoma, which developed in 1 of 5 patients given CNS prophylaxis as compared to 2 of 3 patients without CNS prophylaxis.

Acquired Immunodeficiency Syndrome↗

PubMed1995

A dose comparison study of didanosine in patients with very advanced HIV infection who are intolerant to or clinically deteriorate on zidovudine. German ddI Trial Group.

OBJECTIVE: Zidovudine (ZDV) is the only antiretroviral drug which has been shown to reduce mortality in patients with symptomatic HIV disease, but its use is restricted by intolerance in a significant proportion of patients. Additionally, the efficacy of ZDV therapy appears to decrease after prolonged treatment particularly in the advanced stage of HIV disease. Therefore, alternative antiretroviral regimens for patients are needed. In this study, didanosine (ddI; 2',3'-dideoxyinosine), another HIV reverse transcriptase inhibitor, was evaluated. DESIGN: A total of 426 patients with AIDS or AIDS-related complex (ARC) who were intolerant to or clinically progressing on ZDV therapy and who had CD4+ cell counts < or = 150 x 10(6)/l were randomized to receive either a high (750 mg for bodyweight > or = 60 kg or 500 mg for bodyweight < 60 kg) or a low (200 mg and 134 mg, respectively) dose of ddI daily. SETTING: The patients were recruited from 31 German and Austrian AIDS clinical primary-care centres. RESULTS: The study was stopped after the second interim analysis due to a statistically significant difference in the incidence of pancreatitis (nine versus 26; relative risk, 2.92; P = 0.003) and neuropathy (28 versus 43; relative risk, 1.55; P = 0.05) in favour of the low dose. There was no difference between the low and high dosage groups in survival rate at 6 (80 versus 80%) and 12 months (61 versus 65%), number of deaths [82 (43.6 per 100 patient-years) versus 84 (44.4 per 100 patient-years)], progression from ARC to AIDS or to AIDS or death, or average number of new/recurrent opportunistic infections (2.8 versus 3.0 per patient). CONCLUSIONS: This study cannot conclude on ddI efficacy but it shows that in patients with advanced HIV disease for whom no alternative antiretroviral therapy is available and ddI therapy is considered, daily doses < 750 mg should be administered.

AIDS-Related Complex↗

PubMed1994

Enterocytozoon bieneusi infection in an immunocompetent patient who had acute diarrhea and who was not infected with the human immunodeficiency virus.

Enterocytozoon bieneusi is a microsporidian species that has been detected exclusively in patients infected with human immunodeficiency virus (HIV) who are severely immunocompromised. We report what we believe is the first case of E. bieneusi infection in an HIV-negative patient with acute, self-limited diarrhea whose CD4+ cell count was not depressed.

Acute Disease↗

PubMed1994

Specific diagnosis of progressive multifocal leukoencephalopathy by polymerase chain reaction.

Using polymerase chain reaction (PCR), 34 cerebrospinal fluid (CSF) samples from 28 patients with progressive multifocal leukoencephalopathy (PML) were analyzed. As controls, 116 samples were evaluated from 82 human immunodeficiency virus type 1 (HIV-1)-infected patients and 1 HIV-1-negative patient. Of the HIV-1-positive patients, 23 had cerebral toxoplasmosis, 10 had HIV leukoencephalopathy, and 49 had other neurologic complications. Detection of JC virus (JCV) DNA in CSF was increased 10-fold by the addition of carrier DNA before phenol-chloroform-isoamyl alcohol extraction. The primer pair JC 26/29, from the VP1/large T region, had a limit of detection of 10(5) JCV DNA molecules/100 microL. The primer pair JC 36/39, located in the large T gene region, had a 100-fold lower limit of detection. With JC 26/29, the sensitivity was 43% (12/28) and specificity was 100%. Using JC 36/39, sensitivity increased to 82% (23/28), and false-positive results were not observed. Diagnosis of PML is greatly aided by PCR analysis of CSF.

Base Sequence↗

PubMed1994

Human microsporidiosis.

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AIDS-Related Opportunistic Infections↗

PubMed1994

Effects of high-dose oral acyclovir on herpesvirus disease and survival in patients with advanced HIV disease: a double-blind, placebo-controlled study. European-Australian Acyclovir Study Group.

OBJECTIVE: To determine the efficacy of high-dose oral acyclovir in preventing cytomegalovirus (CMV) and other herpesvirus disease in patients with advanced HIV disease and to evaluate its effect on patient survival. DESIGN: Double-blind, placebo-controlled randomized trial of up to 1 year's therapy. SETTING: Outpatient clinics in 16 hospitals in Europe and Australia. PARTICIPANTS: A total of 302 patients with Centers for Disease Control and Prevention stage IV HIV disease, seropositive for CMV and with CD4+ lymphocyte counts < or = 150 x 10(6)/l. INTERVENTIONS: Oral acyclovir (800 mg, four times daily) or matching placebo for 48 weeks. MAIN OUTCOME MEASURES: Time to development of CMV and other herpesvirus disease. Following the results of another study, the protocol was amended to make survival a second major endpoint. RESULTS: Acyclovir failed to reduce the incidence of CMV disease: the probability of developing CMV disease at 1 year was 0.24 and 0.23 in the placebo and acyclovir groups, respectively (P = 0.53). However, acyclovir significantly reduced the probability of dying at 1 year of follow-up (from 0.39 to 0.23; P = 0.018). As expected, acyclovir significantly reduced the incidence and frequency of herpes simplex virus disease. There were no notable differences between treatment groups in clinically adverse experiences and no changes in haematological parameters to indicate clinically significant drug-induced toxicity. CONCLUSIONS: High-dose acyclovir failed to reduce the incidence of CMV disease, but significantly reduced the probability of dying at 1 year of follow-up.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Successful treatment of AIDS-related pulmonary Kaposi's sarcoma with liposomal daunorubicin.

We report a 35 year old male, human immunodeficiency virus (HIV)-infected patient with acquired immune deficiency syndrome (AIDS), who presented with rapidly progressive pulmonary Kaposi's sarcoma. The tumour regressed with treatment with liposomal daunorubicin and remained in partial remission until the patient died 12 months later from complications of HIV infection. Liposomal daunorubicin may be a safe and effective alternative to the treatment protocols in current use for pulmonary Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗