L-arginine and substance P reverse the pulmonary endothelial dysfunction caused by congenital heart surgery.

Background: The increase in pulmonary vascular resistance (PVR) seen in children after cardiopulmonary bypass has been attributed to transient pulmonary endothelial dysfunction (PED). We therefore examined PED in children with congenital heart disease by assessing the L-arginine-nitric oxide (NO) pathway in terms of substrate supplementation (L-arginine [L-Arg]), stimulation of endogenous NO release (substance P [Sub-P]), and end-product provision (inhaled NO) before and after open heart surgery.

Methods And Results: Ten patients (aged 0.

Potent antiretroviral therapy of primary human immunodeficiency virus type 1 (HIV-1) infection: partial normalization of T lymphocyte subsets and limited reduction of HIV-1 DNA despite clearance of plasma viremia.

Antiretroviral therapy commenced during primary human immunodeficiency virus type 1 (HIV-1) infection (PHI) may limit the extent of viral replication and prevent early loss of HIV-specific CD4 lymphocyte function. We studied the effect of current standard therapy (2 nucleoside analogues and a protease inhibitor) in 16 patients with symptomatic PHI. In the 13 patients who completed 1 year of treatment, plasma HIV RNA was <50 copies/mL and median CD4 cell counts were comparable to HIV-uninfected controls, with naive (CD45RA+CD62L+), primed (CD45RO+), and T cell receptor Vbeta subsets all within normal ranges.

Therapeutic vaccination with p24-VLP and zidovudine augments HIV-specific cytotoxic T lymphocyte activity in asymptomatic HIV-infected individuals.

This study evaluates the impact of therapeutic vaccination with p24-VLP and zidovudine on the induction or maintenance of HIV-specific cytotoxic lymphocyte activity in a cohort of asymptomatic patients with CD4 counts greater than 400 cells/microl. In a dummy, randomized, phase II clinical trial of the therapeutic vaccine, participants were randomized to one of three arms for 6 months: p24-VLP (500 microg) in alum monthly plus zidovudine 200 mg tds, alum adjuvant plus zidovudine, or p24-VLP plus placebo. Subjects were studied for a total of 52 weeks from baseline.

A model of primary HIV-1 infection.

We construct a model based on biological principles of the interaction of HIV-1 with the CD4+ T cells at primary infection. Most of the parameters are obtained from the literature, the remainder from fitting the output of the model to data from seven patients. On the basis of the model we find that initial viral containment is due to an effective immune response.

Effect of protease therapy on cytokine secretion by peripheral blood mononuclear cells (PBMC) from HIV-infected subjects.

The viral load reduction seen in patients with late stage HIV infection treated with the protease inhibitor, ritonavir, is accompanied by increases in the in vitro proliferative responses generated by PBMC. The present study was undertaken to investigate which lymphocyte subsets generated these responses and the effects of therapy on cytokine production. Lymphoproliferation following phytohaemagglutinin (PHA) stimulation was studied by thymidine incorporation, and production of IL-2, interferon-gamma (IFN-gamma) and IL-4 was assessed by ELISA in 12 patients receiving ritonavir and seven receiving placebo in the context of randomized, blinded clinical trials.

Patterns of viral dynamics during primary human immunodeficiency virus type 1 infection. The Sydney Primary HIV Infection Study Group.

This study used curve-fitting techniques to detail the dynamics of human immunodeficiency virus (HIV)-1 and its relationship to circulating T lymphocyte changes in a cohort of 41 male patients (mean age 36+/-7 years) infected with HIV-1. The following characteristics of viral kinetics were obtained: virus load peak, 6. 35+/-0.

Oligoclonal expansions of CD8(+) T cells in chronic HIV infection are antigen specific.

Acute HIV infection is associated with a vigorous immune response characterized by the proliferation of selected T cell receptor V beta (BV)-expressing CD8(+) T cells. These 'expansions', which are commonly detected in the peripheral blood, can persist during chronic HIV infection and may result in the dominance of particular clones. Such clonal populations are most consistent with antigen-driven expansions of CD8(+) T cells.

Effects of IL-2 therapy in asymptomatic HIV-infected individuals on proliferative responses to mitogens, recall antigens and HIV-related antigens.

The effects of IL-2 therapy on lymphoproliferative responses to mitogens, recall antigens and HIV epitopes were studied in asymptomatic HIV-infected patients enrolled in a phase II study of intermittent continuous intravenous (Ci.v.) IL-2 and subcutaneous infusions of polyethylene glycol-modified (PEG) IL-2.

Safety and immunogenicity of a candidate therapeutic vaccine, p24 virus-like particle, combined with zidovudine, in asymptomatic subjects. Community HIV Research Network Investigators.

Objectives: To evaluate the impact of therapeutic immunization with p24 virus-like particle (VLP) and zidovudine (ZDV) on p24 antibody titre (primary endpoint), CD4+ cell counts, cellular responses to the immunogen and recall antigens, and viral load (secondary endpoints) in subjects with asymptomatic HIV infection and CD4+ counts greater than 400 x 10(6) cells/l.

Design: A double dummy, double-blind randomized placebo-controlled Phase II trial of the therapeutic vaccine p24-VLP, with or without ZDV.

Methods: ZDV-naive subjects were randomized to one of three groups for 6 months: group A, ZDV 200 mg three times daily plus intramuscular administration of alum adjuvant monthly; group B, ZDV 200 mg three times daily plus p24-VLP (500 microg) in intramuscular alum monthly; group C, placebo capsules plus p24-VLP (500 microg) in intramuscular alum monthly.

Management of bite wounds and infection in primary care.

This article describes how to recognize the signs of septic arthritis and flexor tenosynovitis after dog bites, how to identify the need for prompt surgical treatment of septic arthritis to prevent joint destruction, how to determine which wounds should and should not be sutured, and how to choose effective antibiotic treatment.

Safety and immunogenicity of UBI HIV-1MN octameric V3 peptide vaccine administered by subcutaneous injection.

Twenty-four HIV-seronegative men, at high risk of HIV infection, were recruited into a phase I/II safety and immunogenicity trial of a prototype HIV vaccine. The immunogen was a synthetic, monovalent, octameric HIV-1MN V3 peptide in an aluminum hydroxide (alum) adjuvant. The vaccine had been evaluated previously using a standard 0-, 1-, 6-month intramuscular schedule and was found to stimulate neutralizing antibody in 60-90% of volunteers.

CD8+ lymphocyte responses to antiretroviral therapy of HIV infection.

CD8+ T lymphocytes may mediate important host responses to human immunodeficiency virus (HIV) infection by human leukocyte antigen (HLA)-restricted cytotoxicity and production of soluble HIV suppressor factors. CD8+ lymphocytes are also important for the suppression of many latent pathogens responsible for opportunistic disease in HIV-infected patients. There has been no systematic analysis of the responses of CD8+ lymphocyte counts to antiretroviral therapy.

Comparison of caudal bupivacaine and diamorphine with caudal bupivacaine alone for repair of hypospadias.

Forty-five boys undergoing repair of hypospadias were allocated randomly to one of two groups. After induction of anaesthesia, 22 patients received 0.25% caudal bupivacaine 0.

Alterations in the immune response of human immunodeficiency virus (HIV)-infected subjects treated with an HIV-specific protease inhibitor, ritonavir.

Effects of a human immunodeficiency virus (HIV) type 1 protease inhibitor, ritonavir, were evaluated in 21 patients enrolled in a phase I/II study. The magnitude and rates of CD4 and CD8 lymphocyte increase, changes in subsets of CD4 and CD8 lymphocytes, and proliferative responses to mitogen and antigens were analyzed. Significant increases were noted in CD4 and CD8 lymphocyte counts; numbers of CD4CD45RO lymphocytes increased significantly by week 1 of therapy.

Managing HIV. Part 1: Principles. 1.2 Strategies of care in managing HIV.

Apply the science, use a team approach, help patients to promote their own health, ensure access to support and accept a public health role. These are the practical lessons of our experience in HIV medicine.

Managing HIV. Part 2: Phases of disease. 2.2 Early HIV-induced immune deficiency.

From the resolution of primary infection until the CD4 cell count falls below 500/microL, people with HIV are usually functioning at their normal capacity physically, mentally and socially. However, HIV is replicating actively within lymph nodes during this period of early immune deficiency. It is important to determine the rate of immune depletion and to assess what factors, if any, may be hastening that progression.

Increasing ciprofloxacin resistance in salmonellas in England and Wales 1991-1994.

Ciprofloxacin is now widely used as the drug of choice for those severe salmonella infections where antibiotic therapy is indicated. Between 1991 and 1994 ciprofloxacin resistance in salmonellas isolated from humans in England and Wales increased from 0.3% to 2.

The role of continuous positive airway pressure during weaning from mechanical ventilation in cardiac surgical patients.

We investigated the effects of providing patients with continuous positive airway pressure during a short weaning period from mechanical ventilation to extubation. Following elective primary aortocoronary bypass surgery employing cardiopulmonary bypass, 80 patients received intermittent positive pressure ventilation for 5 h. At the end of this time patients were randomly allocated to one of the following three groups for a 2 h period of spontaneous respiration prior to extubation: group CPAP0 = T-piece circuit (n = 27); group CPAP5 = 5 cmH2O of continuous positive airway pressure (n = 27); group CPAP10 = 10 cmH2O of continuous positive airway pressure (n = 26).

Cardiac arrest and resuscitation of a 6-month old achondroplastic baby undergoing neurosurgery in the prone position.

We describe the case of a 6-month-old achondroplastic baby who underwent foramen magnum decompression to relieve congenital cervical cord compression. During the procedure, acute hypotension occurred secondary to cord compression, and following attempts to alleviate this, torrential haemorrhage ensued and air was entrained into the circulation through large venous channels in the surgical field. This resulted in an asystolic cardiac arrest from which the baby was resuscitated whilst remaining in the prone position.

Careful planning ensures a happy outcome. Caring for pregnant women with diabetes.

1. It is essential that women with diabetes are offered pre-pregnancy counselling and a shared plan of care during their pregnancy. 2.

Randomized placebo-controlled double-blind study of three aprotinin regimens in primary cardiac surgery.

The serine proteinase inhibitor aprotinin significantly reduces postoperative blood loss in patients requiring cardiac surgery using cardiopulmonary bypass. This study compared two low-dose regimens with administration of high-dose aprotinin and a control protocol to determine whether the dose of aprotinin could be greatly decreased but still maintain efficacy after primary cardiac surgery. Some 100 patients were randomly assigned to one of four groups: control group (0.