Signs and symptoms in common colds.

The patterns of disease caused by five common viruses which infect the respiratory tract are described. The viruses were strains of rhinovirus types 2, 9, and 14, a strain of coronavirus type 229E and of respiratory syncytial virus. Volunteers were given nasal drops containing a low infectious dose of one of the viruses, quarantined from 2 days before to 5 days after inoculation, and examined daily by a clinician using a standard checklist of respiratory signs and symptoms.

Replication of avian influenza viruses in humans.

Volunteers inoculated with avian influenza viruses belonging to subtypes currently circulating in humans (H1N1 and H3N2) were largely refractory to infection. However 11 out of 40 volunteers inoculated with the avian subtypes, H4N8, H6N1, and H10N7, shed virus and had mild clinical symptoms: they did not produce a detectable antibody response. This was presumably because virus multiplication was limited and insufficient to stimulate a detectable primary immune response.

A study of the efficacy of the bradykinin antagonist, NPC 567, in rhinovirus infections in human volunteers.

In a double-blind placebo controlled trial intranasal NPC 567, a bradykinin antagonist, failed to alleviate the symptoms of experimental rhinovirus colds. Indeed, there was evidence that the drug enhanced the symptoms although no irritant effect was detected on the uninfected nasal mucosa.

The time course of the immune response to experimental coronavirus infection of man.

After preliminary trials, the detailed changes in the concentration of specific circulating and local antibodies were followed in 15 volunteers inoculated with coronavirus 229E. Ten of them, who had significantly lower concentrations of pre-existing antibody than the rest, became infected and eight of these developed colds. A limited investigation of circulating lymphocyte populations showed some lymphocytopenia in infected volunteers.

The efficacy of intranasal interferon alpha-2a in respiratory syncytial virus infection in volunteers.

In a double-blind, placebo-controlled study, self-administered intranasal interferon alpha-2a or placebo was given both before and after challenge with respiratory syncytial virus. The incidence of colds and the severity of signs and symptoms were reduced in those receiving interferon alpha-2a as compared with those given placebo. In a further double-blind, placebo-controlled study, self-administered interferon alpha-2a or placebo was given only to those volunteers who developed colds following challenge with respiratory syncytial virus.

Pathogenicity for humans of human rhinovirus type 2 mutants resistant to or dependent on chalcone Ro 09-0410.

Mutants of human rhinovirus type 2 (HRV-2) resistant to and dependent on the antirhinoviral compound chalcone Ro 09-0410 were selected in cell culture under clean laboratory conditions. A total of 42 volunteers were challenged with either the drug-resistant mutant [SR2-410(r)] (15 volunteers), the drug-dependent mutant [SR2-410(d)] (15 volunteers), or a wild-type HRV-2 which had a similar passage level in vitro as the mutants but without the drug (12 volunteers). Of volunteers challenged with the wild-type HRV-2, 33, 67, and 82% developed cold symptoms, shed virus, and showed serological evidence of infection, respectively.

The effect of intranasal nedocromil sodium on viral upper respiratory tract infections in human volunteers.

Two studies involving double-blind group comparative trials in human volunteers compared the effects of intranasal nedocromil sodium (2.6 mg active drug per nostril, q.i.

The time course of the humoral immune response to rhinovirus infection.

The specific humoral immune response of 17 volunteers to infection with human rhinovirus type 2 (HRV-2) has been measured both by neutralization and by ELISA. Six volunteers who had HRV-2-specific antibodies in either serum or nasal secretions before HRV-2 inoculation were resistant to infection and illness. Of the remaining 11 volunteers who had little pre-existing HRV-2-specific antibody, one was immune but 10 became infected and displayed increases in HRV-2-specific antibodies.

A note on the failure of CGP 19835 A (MTP-PE) to influence the course of influenza A2 infection in human volunteers.

A single dose of the immunomodulator CGP A (MTP-PE) given intranasally to human volunteers 24 h prior to challenge with influenza A2 virus failed to protect against infection or ameriolate any subsequent illness.

Local hyperthermia benefits natural and experimental common colds.

Objective: To determine whether inhaling fully humidified air at 43 degrees C gave more benefit to cold sufferers than inhaling air at 30 degrees C.

Design: Randomised double blind trial. Setting--General practice and the common cold research unit.

Failure to demonstrate synergy between interferon-alpha and a synthetic antiviral, enviroxime, in rhinovirus infections in volunteers.

Marked synergy between the antirhinoviral effect of rHuIFN alpha and enviroxime has been observed in vitro but an attempt to demonstrate it in volunteers was unsuccessful. The sub-optimal intranasal dose of rHuIFN alpha (0.18 Mu four times daily for 4 1/4 days) used prophylactically in the trial did reduce the severity of colds induced by RV9 and 14, but the difference did not reach statistical significance and was not enhanced by the administration of enviroxime (0.

Recombinant human interferon-gamma as prophylaxis against rhinovirus colds in volunteers.

The first evaluation of intranasal (i.n.) recombinant human interferon-gamma (rHuIFN-gamma) as prophylaxis against experimental rhinovirus (RV) infection and illness in volunteers is reported.

Evaluation of an enzyme-linked immunosorbent assay that measures rhinovirus-specific antibodies in human sera and nasal secretions.

Rhinovirus-specific antibodies have traditionally been detected by their ability to neutralise the homologous rhinovirus serotype in tissue culture. Recently, however, we have described an enzyme-linked immunosorbent assay that detects rhinovirus-specific antibodies in sera and nasal secretions [Barclay and Al-Nakib, 1987]. Here we describe an evaluation of the ELISA in a study involving 71 adult volunteers inoculated intranasally with human rhinovirus type 2 (HRV-2).

Towards anti-HIV vaccines.

There is a great deal of experience on the development and testing of antiviral vaccines but, in the case of HIV, it will be necessary to analyse carefully our understanding of the biology of the organism, the natural history and pathology of the disease (in particular immunity or resistance to infection or clinical symptoms), the possible sources of antigens and methods of formulating and administering them. Only then, and after successful initial trials, will it be possible to propose rational programmes for their use. This article indicates how discussions will be structured and the directions in which they might go, but needs to be supplemented by much more factual information and refined with further opinions and judgements on probable outcomes.

Air, antibiotics and sepsis in replacement joints.

Reducing bacterial contamination of the wound by limiting dispersal from the operating staff through the wearing of special occlusive clothing and by employing directional flow ventilating systems substantially reduces the risk of later joint sepsis. Inhibiting growth of those bacteria which reach the wound, by means of perioperative antibiotics, further reduces the incidence of joint sepsis. When all three means are used together the sepsis rate in the years after operation can be reduced to no more than a few per thousand.

Influence of atopy on the clinical manifestations of coronavirus infection in adult volunteers.

In an attempt to understand the relationship between viral upper respiratory tract infection and the underlying virological and immunological mechanisms, thirty-four volunteers were inoculated intranasally with coronavirus 229E; subsequent virus shedding and/or antibody rises, indicating active infection, were observed in twenty-nine. There was a greater increase in independently measured scores of clinical severity, e.g.

Prophylaxis and treatment of rhinovirus colds with zinc gluconate lozenges.

Following a tolerance study, double-blind placebo controlled trials were conducted to determine the prophylactic effect of zinc gluconate lozenges on rhinovirus challenge and, in a third study, their therapeutic efficacy when given at the start of colds caused by virus inoculation was tested. In the prophylaxis study a total of 57 volunteers received lozenges of either zinc gluconate (23 mg) (29 volunteers) or matched placebo (28 volunteers) every 2 h while awake during a period of four and a half days. They were challenged with 10(2) tissue culture infecting dose (TCID50) of human rhinovirus 2 (HRV-2) on the second day of medication, and were monitored daily for symptoms and signs of colds and laboratory evidence of infection.

Intranasal chalcone, Ro 09-0410, as prophylaxis against rhinovirus infection in human volunteers.

The antirhinovirus agent chalcone Ro 09-0410 was tested in double-blind place-controlled volunteer trials for its protective efficacy against experimental rhinovirus infection. Fifty volunteers received either drug (26 volunteers) or placebo (24 volunteers) both before and after challenge with 20-40 tissue culture infecting dose (TCID50) of human rhinovirus 2 (RV2). There was no evidence that medication significantly reduced the incidence of infection or illness, indeed there was some increase in the nasal secretion produced.

A 'new' generation of more potent synthetic antirhinovirus compounds: comparison of their MICs and their synergistic interactions.

A 'new' generation of synthetic antirhinovirus compounds has recently become available for in vitro evaluation. Thus a new group of compounds from Janssen was found to be 10-fold more active than enviroxime or 57-fold more active than dichloroflavan (DCF), against human rhinovirus 9 (HRV-9). In addition, they were also some 5- and 10-fold more potent than enviroxime and DCF, respectively, against HRV-2.

Direct detection of rhinoviruses by an enzyme-linked immunosorbent assay.

This paper describes the first enzyme-linked immunosorbent assay for the detection of rhinovirus antigens in clinical specimens (nasal washings), either directly or following overnight cell culture amplification. The assay takes approximately 48 hours to perform and utilizes the same rabbit antirhinovirus hyperimmune serum as both the capture and detecting antibody. The latter has been biotin-labelled and is detected via a streptavidin beta-galactosidase preformed complex.

Studies of rhinovirus resistant to an antiviral chalcone.

During studies of the antiviral activity of chalcone Ro-09-0410 on human rhinovirus type 9 (RV9) chalcone-resistant strains of RV9 were isolated and appeared with a frequency of about 10(-5) in chalcone sensitive stock. Chalcone-dependent viruses were found after further passage. Some characteristics of the resistant viruses were studied and compared with those of the wild type virus; a number of differences were detected.

Growth and Pathogenesis of Mycoplasma mycoides var. capri in Chicken Embryo Tracheal Organ Cultures.

The growth and pathogenicity of Mycoplasma mycoides var. capri were studied in chicken embryo tracheal rings in rolled tubes. In these organ cultures, M.