Simultaneous application of transcranial magnetic stimulation and low-frequency electrostatic field as treatment of carbohydrate and lipid disorders in patients with metabolic syndrome.

The metabolic syndrome, which covers a wide variety of pathological concerns, is rapidly becoming a global pandemic. This syndrome is difficult to treat pharmacologically. Physiotherapy techniques, which have both local and systemic effects, can be employed as a suitable substitute. The purpose of this study was to investigate the therapeutic effects of a program of simultaneous physiotherapy that included migrant transcranial magnetic stimulation (TMS) and the exposure to an alternating low-frequency electrostatic field (LFEF) in the treatment of metabolic syndrome patients. Ninety patients were randomly assigned to three study groups. While continuing the usual drug therapy the first group (30 patients) received LFEF intervention, the second group (30 patients) received TMS, and the third group (30 patients) underwent the simultaneous use of these non-invasive techniques (LFEF + TMS). All treatments involved 10 sessions with daily frequency. In all the patients before and after treatment body weight, blood pressure parameters, levels of insulin, cortisol, glucose, total cholesterol, high density lipoproteins, malondialdehyde, and Schiff bases, the activity of the antioxidant enzymes catalase and of the superoxide dismutase were studied. The changes in the outcomes assessed revealed a different reaction to therapy with LFEF or TMS, as well as a greater benefit when both treatments were used at the same time. A simultaneous LFEF and TMS intervention seems a promising resource for the treatment of the metabolic syndrome, particularly of the lipid and carbohydrate metabolism disorders. However, further studies are needed to confirm these findings and investigate the underlying mechanisms.

Residual human immunodeficiency virus (HIV) Type 1 RNA and DNA in lymph nodes and HIV RNA in genital secretions and in cerebrospinal fluid after suppression of viremia for 2 years.

Residual viral replication persists in a significant proportion of human immunodeficiency virus (HIV)-infected patients receiving potent antiretroviral therapy. To determine the source of this virus, levels of HIV RNA and DNA from lymphoid tissues and levels of viral RNA in serum, cerebrospinal fluid (CSF), and genital secretions in 28 patients treated for < or =2.5 years with indinavir, zidovudine, and lamivudine were examined. Both HIV RNA and DNA remained detectable in all lymph nodes. In contrast, HIV RNA was not detected in 20 of 23 genital secretions or in any of 13 CSF samples after 2 years of treatment. HIV envelope sequence data from plasma and lymph nodes from 4 patients demonstrated sequence divergence, which suggests varying degrees of residual viral replication in 3 and absence in 1 patient. In patients receiving potent antiretroviral therapy, the greatest virus burden may continue to be in lymphoid tissues rather than in central nervous system or genitourinary compartments.

Two double-blinded, randomized, comparative trials of 4 human immunodeficiency virus type 1 (HIV-1) envelope vaccines in HIV-1-infected individuals across a spectrum of disease severity: AIDS Clinical Trials Groups 209 and 214.

The potential role of human immunodeficiency virus type 1 (HIV-1)-specific immune responses in controlling viral replication in vivo has stimulated interest in enhancing virus-specific immunity by vaccinating infected individuals with HIV-1 or its components. These studies were undertaken to define patient populations most likely to respond to vaccination, with the induction of novel HIV-1-specific cellular immune responses, and to compare the safety and immunogenicity of several candidate recombinant HIV-1 envelope vaccines and adjuvants. New lymphoproliferative responses (LPRs) developed in <30% of vaccine recipients. LPRs were elicited primarily in study participants with a CD4 cell count >350 cells/mm(3) and were usually strain restricted. Responders tended to be more likely than nonresponders to have an undetectable level of HIV-1 RNA at baseline (P=.067). Induction of new cellular immune responses by HIV-1 envelope vaccines is a function of the immunologic stage of disease and baseline plasma HIV-1 RNA level and exhibits considerable vaccine strain specificity.

Shipment impairs lymphocyte proliferative responses to microbial antigens.

Lymphocyte proliferation assays (LPAs) are widely used to assess T-lymphocyte function of patients with human immunodeficiency virus infection and other primary and secondary immunodeficiency disorders. Since these assays require expertise not readily available at all clinical sites, specimens may be shipped to central labs for testing. We conducted a large multicenter study to evaluate the effects of shipping on assay performance and found significant loss of LPA activity. This may lead to erroneous results for individual subjects and introduce bias into multicenter trials.

3-year suppression of HIV viremia with indinavir, zidovudine, and lamivudine.

BACKGROUND: Antiretroviral regimens containing HIV protease inhibitors suppress viremia in HIV-infected patients, but the durability of this effect is not known. OBJECTIVE: To describe the 3-year follow-up of patients randomly assigned to receive indinavir, zidovudine, and lamivudine in an ongoing clinical trial. DESIGN: Open-label extension of a randomized, double-blind study. SETTING: Four clinical research units. PATIENTS: 33 HIV-infected, zidovudine-experienced patients with serum HIV RNA levels of at least 20,000 copies/mL and CD4 counts ranging from 50 to 400 cells/mm3. INTERVENTION: Indinavir, zidovudine, and lamivudine. MEASUREMENTS: Safety assessments, HIV RNA levels, CD4 cell counts, and genotypic analyses. RESULTS: After 3 years of follow-up, 21 of 31 contributing patients (68% [95% CI, 49% to 83%]) had serum viral load levels less than 500 copies/mL. Twenty of 31 (65% [CI, 45% to 80%]) had levels less than 50 copies/mL. The median increase in CD4 count from baseline was 230 cells/mm3 (interquartile range, 150 to 316 cells/mm3). Nephrolithiasis occurred in 12 of 33 patients (36%). CONCLUSION: A three-drug regimen of indinavir, zidovudine, and lamivudine suppressed viremia in two thirds of patients for at least 3 years.

Phase I studies of hypericin, the active compound in St. John's Wort, as an antiretroviral agent in HIV-infected adults. AIDS Clinical Trials Group Protocols 150 and 258.

BACKGROUND: Hypericin, the active compound in St. John's Wort, has antiretroviral activity in vitro. Many HIV-infected persons use St. John's wort. OBJECTIVE: To evaluate the safety and antiretroviral activity of hypericin in HIV-infected patients. DESIGN: Phase I study. SETTING: Four clinical research units. PATIENTS: 30 HIV-infected patients with CD4 counts less than 350 cells/mm3. INTERVENTION: Intravenous hypericin, 0.25 or 0.5 mg/kg of body weight twice weekly or 0.25 mg/kg three times weekly, or oral hypericin, 0.5 mg/kg daily. MEASUREMENTS: Safety was assessed at weekly visits. Antiretroviral activity was assessed by changes in HIV p24 antigen level, HIV titer, HIV RNA copies, and CD4 cell counts. RESULTS: Of the 30 patients who were enrolled, 16 discontinued treatment early because of toxic effects. Severe cutaneous phototoxicity was observed in 11 of 23 (48% [95% CI, 27% to 69%]) evaluable patients, and dose escalation could not be completed. Virologic markers and CD4 cell count did not significantly change. CONCLUSIONS: Hypericin caused significant phototoxicity and had no antiretroviral activity in the limited number of patients studied.

Delayed-type hypersensitivity to recombinant HIV envelope glycoprotein (rgp160) after immunization with homologous antigen.

Delayed-type hypersensitivity (DTH) responses to intradermal recombinant HIV envelope glycoprotein (rgp160) may assess cell-mediated immune responses to HIV envelope. In three studies, DTH and lymphocyte proliferation responses to rgp160 were obtained in a total of 106 HIV-seropositive subjects with CD4+ counts >400 cells/mm3. Several subjects participated in more than one study. Before immunization, DTH responses were seen in 5 of 56 (9%) of HIV-infected study subjects. After immunization with an alum-adjuvanted experimental rgp160 vaccine, DTH responses were seen in 46 of 52 (89%). Using in vitro lymphocyte proliferation activity (LPA) to rgp160 as an indication of cellular immune response, skin testing has a sensitivity of 0.75 (95% confidence Interval [CI], 0.59-0.88) and a specificity of 0.84 (95% CI, 0.72-0.92). Biopsy samples of skin that had tested positive confirmed the presence of a DTH reaction with a predominance of CD4+ T cells in the perivascular, inflammatory infiltrate. Skin testing before and after immunization with candidate AIDS vaccines could provide a simple method in the field to assess new cell mediated immune responses.

Lymphocyte-proliferative responses to HIV antigens as a potential measure of immunological reconstitution in HIV disease.

Lymphocyte-proliferative responses (LPRs) to HIV antigens are absent or of low magnitude in the majority of HIV-infected individuals, even early in the disease. However, lymphocytes from 2% to 3% of individuals proliferate very strongly to HIV Env or Gag antigens, and these individuals remain well clinically, without antiretroviral therapy. In established HIV infection, suppression of HIV-replication with potent antiretroviral therapy does not result in the development of strong LPRs to HIV antigens. Large LPRs to HIV antigens can be induced by HIV vaccines in patients with established infection, even though they were not formed in response to infection. Studies must be designed to determine whether large LPRs induced by vaccines administered in conjunction with potent antiretroviral therapy are associated with long-term control of HIV infection.

Empowerment: family-centred care.

The major findings from interviews with qualified children's nurses, analysed using a grounded theory approach, were that children's nurses have the necessary theoretical knowledge to empower families, but they require educational and training opportunities in family empowerment. It was also established that a working environment that promotes its translation into everyday practice and supports them in an empowering model of care for children and families is necessary.

The clinical educator role.

Role of the clinical educator is presented. Questionnaire survey of 60 staff was undertaken. Meeting staff's continuing education needs is important. Ensuring roles are responsive to needs of practitioners, children and families is vital. Quality education equals quality services.

Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy.

BACKGROUND: The new protease inhibitors are potent inhibitors of the human immunodeficiency virus (HIV), and in combination with other antiretroviral drugs they may be able to cause profound and sustained suppression of HIV replication. METHODS: In this double-blind study, 97 HIV-infected patients who had received zidovudine treatment for at least 6 months and had 50 to 400 CD4 cells per cubic millimeter and at least 20,000 copies of HIV RNA per milliliter were randomly assigned to one of three treatments for up to 52 weeks: 800 mg of indinavir every eight hours; 200 mg of zidovudine every eight hours combined with 150 mg of lamivudine twice daily; or all three drugs. The patients were followed to monitor the occurrence of adverse events and changes in viral load and CD4 cell counts. RESULTS: The decrease in HIV RNA over the first 24 weeks was greater in the three-drug group than in the other groups (P<0.001 for each comparison). RNA levels decreased to less than 500 copies per milliliter at week 24 in 28 of 31 patients in the three-drug group (90 percent), 12 of 28 patients in the indinavir group (43 percent), and none of 30 patients in the zidovudine-lamivudine group. The increase in CD4 cell counts over the first 24 weeks was greater in the two groups receiving indinavir than in the zidovudine-lamivudine group (P< or =0.01 for each comparison). The changes in the viral load and the CD4 cell count persisted for up to 52 weeks. All the regimens were generally well tolerated. CONCLUSIONS: In most HIV-infected patients with prior antiretroviral therapy, the combination of indinavir, zidovudine, and lamivudine reduces levels of HIV RNA to less than 500 copies per milliliter for as long as one year.

Effect of therapeutic immunization with recombinant gp160 HIV-1 vaccine on HIV-1 proviral DNA and plasma RNA: relationship to cellular immune responses.

Therapeutic vaccination has been proposed as a strategy to augment immune mechanisms to control viral replication and slow clinical progression of HIV infection to disease. Following recombinant gp160 (r-gp160) immunization in three clinical trials, plasma HIV-1 RNA and cellular proviral DNA were assessed by quantitative polymerase chain reaction (PCR) in 76 HIV-seropositive subjects with CD4+ T cell counts > or = 300/mm3. Immunization increased HIV-specific cellular immune responses (e.g., cytotoxic T lymphocyte [CTL] activities, lymphocyte proliferative responses); however, there were no significant effects of immunization or cellular immune responses on measures of plasma RNA or cellular DNA viral load.

A randomized, placebo-controlled study of the immunogenicity of human immunodeficiency virus (HIV) rgp160 vaccine in HIV-infected subjects with > or = 400/mm3 CD4 T lymphocytes (AIDS Clinical Trials Group Protocol 137).

Immune responses provoked by human immunodeficiency virus (HIV) infection ultimately are insufficient to control the disease and do not include strong lymphocyte-proliferative responses to HIV antigens or antibodies to many viral epitopes. A randomized double-blind, placebo-controlled trial evaluated the immunogenicity of recombinant HIV envelope vaccine (rgp160) in HIV-infected subjects with > or = 400/mm3 CD4 T cells. Controls received hepatitis B vaccine. Of subjects receiving rgp160, 98% developed lymphocyte-proliferative responses to the immunogen, 33% to a different envelope protein, and 56% and 60% to p24 and p66, respectively. All doses of vaccine (20, 80, 320, 1280 microgram) induced new responses. New antibodies to epitopes on rgp160 developed only in recipients of higher doses of rgp160. CD4 T cell percentages declined less rapidly in recipients of rgp160 than in controls. Vaccination of HIV-infected subjects with rgp160 results in cellular and humoral immune responses to HIV that infection itself had not stimulated.

CD4+ blood lymphocytes are rapidly killed in vitro by contact with autologous human immunodeficiency virus-infected cells.

We have investigated the ability of human immunodeficiency virus (HIV)-infected cells to kill uninfected CD4+ lymphocytes. Infected peripheral blood mononuclear cells were cocultured with autologous 51Cr-labeled uninfected cells. Rapid death of the normal CD4-expressing target population was observed following a brief incubation. Death of blood CD4+ lymphocytes occurred before syncytium formation could be detected or productive viral infection established in the normal target cells. Cytolysis could not be induced by free virus, was dependent on gp120-CD4 binding, and occurred in resting, as well as activated, lymphocytes. CD8+ cells were not involved in this phenomenon, since HIV-infected CEMT4 cells (CD4+, CD8- cells) mediated the cytolysis of uninfected targets. Reciprocal isotope-labeling experiments demonstrated that infected CEMT4 cells did not die in parallel with their targets. The uninfected target cells manifested DNA fragmentation, followed by the release of the 51Cr label. Thus, in HIV patients, infected lymphocytes may cause the depletion of the much larger population of uninfected CD4+ cells without actually infecting them, by triggering an apoptotic death.

Analysis of potential risk factors associated with the development of pancreatitis in phase I patients with AIDS or AIDS-related complex receiving didanosine.

Phase I dose-escalating trials of didanosine revealed dose-limiting toxicities, including pancreatitis, and established a total daily dose of 12.5 mg/kg/day as the maximum tolerated dose. Clinical and pharmacokinetic data of 61 patients from two trials were analyzed to further evaluate the risk of pancreatitis: 1 (6.3%) of 16 patients who received < 500 mg/day didanosine, 2 (13.3%) of 15 who received 500-750 mg/day, and 15 (50%) of 30 who received > 750 mg/day developed pancreatitis (P < .001). A relationship between risk of pancreatitis and steady-state plasma concentrations of didanosine and age was also observed, suggesting that knowledge of didanosine pharmacokinetics provided additional information regarding risk of toxicity. Further confirmation of these findings will be necessary to determine if the risk factors for pancreatitis remain the same at lower doses currently used.