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Biomedical subjects

D S Freestone

Publications and source records attributed to D S Freestone.

At least 19 recordsLinked to original sources
PubMed1995

Conflict of interests: an introduction.

In earlier times, clinical researchers published the results of their studies as seemed most appropriate to them. In an increasingly computerized and communicative environment this is no longer satisfactory, since now there are a number of other groups whose interests need to be taken into account. These include patients, medical journals, the Stock Exchange, the media and the law. This supplement arises out of a meeting established to describe the methods used to communicate clinical research results, the timing and the needs of other groups in an attempt to improve understanding and to identify preferred practice. Avoidance by clinical investigators of conflict of interest and accusations of improper practice clearly merit discussion.

Clinical Trials as Topic↗
PubMed1993

Inappropriate publication of trial results and potential for allegations of illegal share dealing.

There is increasing evidence of fraud in clinical research, and one aspect concerns trading in pharmaceutical company shares by people who may have confidential information about the results of clinical trials. Plainly this has implications for honest investigators, who may find themselves exposed to such allegations. In this paper Dr D S Freestone and Mr H Mitchell, QC, identify three interlinked issues which they think underlie the potential for these allegations. They are pressure for premature or inappropriate communication of research results; trading in pharmaceutical company shares by academic clinical investigators; and the possibility that clinical investigators might succumb to temptation. Dr Freestone and Mr Mitchell suggest that whenever possible results of clinical studies should be published in appropriate medical journals without prior public disclosure. This conflicts with Stock Exchange rules, which require that price sensitive information should be published at the earliest opportunity and preclude priority of publication in medical journals. Freestone and Mitchell believe that rarely rapid public disclosure is acceptable if it is to protect patients' interests but that it must not prejudice publication in the medical or scientific press. When rapid public disclosure is needed, they say, every attempt should be made to inform prescribers before patients. Dr Freestone and Mr Mitchell warn that academic clinical investigators who have access to unpublished price sensitive information about pharmaceutical companies whose shares they trade in will almost certainly be in breach of the Company Securities (Insider Dealing) Act 1985. Furthermore, disclosing such information to third parties, they say, exposes those people also to potential criminal liability. Freestone and Mitchell advise that when potential for allegations of conflict of interest exists clinical investigators should consider declaring their position to ethics committees and any sponsoring organisations.

Biomedical Research↗
PubMed1992

Zidovudine.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Failure of intranasally administered 4', 6-dichloroflavan to protect against rhinovirus infection in man.

4',6-Dichloroflavan, a potent inhibitor of rhinovirus replication in tissue culture systems was tested in a double-blind, placebo-controlled volunteer trial for its protective efficacy against experimental rhinovirus infection. Dichloroflavan was administered intranasally as a 5 per cent w/v aqueous suspension (40 mg; 5 times per day) for 5 doses before and 21 doses after intranasal challenge with rhinovirus type 9, a virus type known to be highly sensitive to the drug when tested in tissue culture. A total of 49 volunteers were included in the efficacy analysis. Dichloroflavan did not produce any consistent or significant reduction in clinical or laboratory parameters of infection. Indeed there was some indication that treatment with the drug may have been associated with increased severity of clinical signs and symptoms. Dichloroflavan administered intranasally is not, therefore, of value in the prevention of human rhinovirus infection.

Administration, Intranasal↗
PubMed1985

The need for new antiviral agents.

Population density and immune status, vectors and virulence of infection, nutritional status, sanitation, genetic susceptibility and medical management of cases, are important factors influencing the incidence and/or severity of virus infections. Thus, the prevalence and clinical importance of virus infections and the need for antiviral drugs differ from place to place and from time to time. National and World Health Statistics of notifications of disease give some index of the incidence of infections but not all virus infections are notifiable. Such statistics can be misleading also through failures to notify from sloth on the part of the physician or, in the absence of pathognomonic symptoms or signs, from errors in diagnosis. Any assessment of the need for new antiviral drugs should consider the availability, safety, effectiveness and cost of alternative measures, including prevention of spread of infection by control of vectors, immunization by use of viral vaccines, or treatment with existing antiviral drugs. Early start of treatment of acute virus infections with existing drugs gives the best results and, where the clinical diagnosis is uncertain, accurate rapid virus diagnosis is of paramount importance. Many virus infections are asymptomatic or of trivial importance and without sequelae. However, new or improved antiviral drugs are needed for the prevention and/or treatment of a number of significant conditions caused by viruses which are not at present adequately controlled. These include upper and lower respiratory tract infections, influenza, chronic hepatitis, gastroenteritis, infectious mononucleosis, measles, rabies, haemorrhagic fevers and warts. Furthermore, such drugs might prove of therapeutic value in the prevention or treatment of virus-associated tumours, such as hepatoma, nasopharyngeal carcinoma, Burkitt's lymphoma, Kaposi's sarcoma and possibly carcinoma of the cervix.

Antiviral Agents↗
PubMed1984

Intranasal lymphoblastoid interferon ("Wellferon") prophylaxis against rhinovirus and influenza virus in volunteers.

Purified lymphoblastoid interferon (HuIFN-alpha) or placebo was self-administered intranasally by volunteers using a spray device three times daily for four and one-third days beginning one day before virus challenge. Each subject received a total dose of 35.1 Mu of interferon (IFN) administered in 13 equal doses of 2.7 Mu. Doses were administered in a volume of 0.2 ml (0.1 ml to each nostril). The first group received human rhinoviruses types 9 and 14. There were no significant colds in 19 volunteers receiving IFN and 7 in 23 volunteers receiving placebo (p less than 0.05). Serological responses and/or recovery of challenge virus were obtained in 14 (74%) recipients of IFN and in all 23 recipients of placebo (p less than 0.05). Mean daily and total clinical scores and mean daily and total nasal secretion weights were significantly greater in those receiving placebo than in those given IFN. The second group received influenza virus A/Eng/40/83. There were 4 significant illnesses in 13 volunteers receiving IFN and 10 in 17 volunteers receiving placebo (p greater than 0.05). Serological responses and/or recovery of challenge virus were obtained in 11 volunteers receiving IFN and 14 volunteers receiving placebo. Mean daily secretion weight and mean clinical scores were lower in those given IFN than in those given placebo - the differences were significant for clinical score on 2 days. The results suggest that IFN prophylaxis was less effective against influenza A than against rhinovirus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

Failure of oral 4',6-dichloroflavan to protect against rhinovirus infection in man.

4',6-Dichloroflavan, a potent inhibitor of rhinovirus replication in vitro, was tested in a double-blind placebo controlled volunteer trial for its protective effect against experimental rhinovirus infection. Dichloroflavan was given orally (1 mg/kg, 3 times per day) for 3 doses before, and 13 doses after intranasal challenge with rhinovirus type 9, a type known to be highly sensitive in tissue culture. A total of 63 volunteers were included in the analysis for efficacy. Dichloroflavan did not produce any consistent or significant reduction in quantitative clinical or laboratory evidence of infection, and there was no apparent negative correlation of such data with drug concentrations in plasma. It is concluded that administration of dichloroflavan in the oral formulation tested is not of value in the treatment of human rhinovirus infection.

Adolescent↗
PubMed1983

Medical research council trial of antilymphocyte globulin in renal transplantation. A multicenter randomized double-blind placebo controlled clinical investigation.

A total of 173 patients who received live donor or cadaveric primary or secondary renal transplants at five British hospitals were entered into a randomized double-blind controlled clinical trial of equine antilymphocyte globulin (ALG) administered prophylactically to prevent rejection. The ALG was prepared in the early 1970s and used cultured human lymphoblasts as antigen. Following transplantation all patients were treated with a standard immunosuppressant regimen of steroids and azathioprine and, in addition, were given either 30 mg/kg ALG or placebo daily for 10 days by intravenous infusion. In comparison with more recently produced materials, the ALG employed in this study was of moderate potency in prolonging skin graft survival in monkeys. Primary graft failure occurred in 27 patients (15/86 ALG and 12/87 placebo). At three to five years after transplantation 50 of the remaining patients had died, almost all from diseases relating to their renal condition, and 25 more had suffered complete graft failure. No significant differences were found between patients treated with ALG and placebo in the numbers with functioning grafts during the 3 years following transplantation, in the time between transplantation and the first rejection episode, or in the number of episodes during the first six months after transplantation. This applied whether live or cadaveric grafts were employed. Within the first 6 months of operation, infection was given as a major contributory cause of death in 12 patients treated with ALG and in 5 who received placebo (P greater than 0.1). Infections were also slightly more common during the two weeks following transplantation in those receiving ALG (13/86 ALG, 10/87 placebo). As expected, graft survival was significantly better in patients who received live donor grafts (P = 0.001) and in patients with the least donor-recipient histocompatibility mismatches (P = 0.008). The results of this multicenter trial show no therapeutic benefit to renal graft recipients from the administration of ALG, and suggest that the risks of fatal infection may have been aggravated. Use of such equine ALG in similar dose regimens is therefore, not, justified in renal transplantation, especially if some part of the apparent effects on fatal infections is real. It is stressed that these findings are relevant only to the equine ALG used in this study, which was raised with cultured human lymphoblasts as the antigen, and to ALG prepared in a similar way and of similar potency. It should not be inferred that these results are applicable to ALG prepared in other ways.

Adolescent↗
PubMed1981

Trimethoprim and co-trimoxazole in the treatment of acute urinary tract infections: patient compliance and efficacy.

Patient compliance and drug efficacy and side-effects were compared in two groups of patients with symptoms of acute lower urinary tract infections. One group was treated with trimethoprim, one tablet (300 mg) once a day, and the other with co-trimoxazole, two tablets (160 mg trimethoprim, 800 mg sulphamethoxazole) twice a day; both treatments were prescribed for seven days. Patient compliance was significantly greater with trimethoprim: corrected percentage compliance rates were 97.5 per cent for trimethoprim and 79.1 per cent for co-trimoxazole (p<0.05). Trimethoprim and co-trimoxazole were of equivalent effectiveness in the control of symptoms. Side-effects were more frequent with co-trimoxazole, but the difference was not significant.

Acute Disease↗
PubMed1980

Comparison of antibody responses and virus shedding following administration of trivalent oral poliomyelitis vaccines prepared either in monkey or human diploid cell substrates.

Nineteen (22.9%) of 83 sera collected before vaccination from adult volunteers aged 21-64 years were without neutralizing antibody to poliomyelitis at levels of 0.15 i.u./ml for types I and II and 0.1 i.u./ml for type III. Some correlations were found between the history of previous vaccination and the presence of antibody but these were not well defined. Vaccination with a single dose of trivalent oral polio vaccine elicited fourfold or greater antibody responses to one or more poliomyelitis types in 53 (63.9%) volunteers, the percentage antibody resposnes being inversely related to the titre of antibody present before vaccination. Types I, II or III poliomyelitis virus were recovered from 76.8% of faecal samples collected 1 week after vaccination. The percentage recovery progressively declined thereafter until virus was recovered from 10.5% of samples collected 6 weeks after vaccination. Type for type, the titres and percentages of antibody responses and virus shedding in faeces were similar following trivalent oral poliomyelitis vaccines whether prepared in monkey or human diploid cell substrates. Some change in reproductive capacity temperature (r.c.t./40) marker was found in faecal isolates from volunteers vaccinated with monkey kidney and human diploid grown vaccines but no change in 'd' marker was found.

Adult↗
PubMed1979

Prevention of necrotising enteritis in Papua New Guinea by active immunisation.

Necrotising enteritis (pig-bel) caused by Clostridium welchii type C is a major cause of illness and death in the Highlands of Papua New Guinea. In a controlled trial of active immunisation with a clostridial toxoid prepared from type-C cultures the incidence of pig-bel in over 2500 immunised children within 24 months of immunisation was less than an eighth of that in a control group. Necrotising enteritis in Papua New Guinea is now a preventable disease.

Adolescent↗
PubMed1979

Development, preparation and safety testing of a Clostridium welchii type C toxoid. I: preliminary observations in man in Papua New Guinea.

The reactogenicity and immunogenicity of various strengths of plain and adsorbed Cl. welchii type C toxoid have been evaluated in laboratory tests and in man in Papua New Guinea. The greater antigenicity and acceptable clinical reactivity of a vaccine containing 50 total combining power units per 0.5 mm of adsorbed toxoid resulted in its selection for further field studies.

Adult↗
PubMed1979

Antibody responses to vaccination with WRL 105 strain live influenza vaccine in previously vaccinated and unvaccinated volunteers.

Intranasal vaccination with a single 0.5 ml dose of 10(7.0) EID 50 WRL 105 strain live influenza vaccine elicited four-fold or greater increases in circulating homotypic haemagglutinating inhibiting (HAI) antibody in 60 (64.5%) of 93 volunteers, or in 58 (74.4%) of 78 volunteers with HAI antibody titres before vaccination of less than or equal to 1/20. In comparison, in a group of volunteers vaccinated 9 months previously re-vaccination elicited antibody responses in only 4 (6.9%) of 58 volunteers, or in 3 (14.3%) of 21 volunteers with antibody titres before vaccination of less than or equal to 1/20. Titres of vaccine-induced antibody and antibody resulting from earlier natural infection appeared to fall slowly and at equivalent rates over a 9 month period.

Adult↗
PubMed1979

The prevention of pig-bel in Papua New Guinea.

In many Highlands hospitals pig-bel is the commonest cause of death in children over 12 months of age. In a double blind controlled trial in Sina Sina we have shown that Clostridium welchii type C beta toxoid (beta toxoid) protects against pig-bel (p < 0.02). Of 2,538 children given beta toxoid, two developed pig-bel in the following two years. Seventeen of 2,532 control children vaccinated with tetanus toxoid developed pig-bel. We suggest that beta toxoid be given to Highlands children at two, four and six months of age. Boosters may be needed. Health services in the Highlands need to be improved so that this vaccine can be effectively delivered.

Adolescent↗
PubMed1979

Problems in the investigation of adverse reactions.

All drugs and vaccines administered to man cause adverse reactions. In general the adverse reaction profile of a new vaccine should be defined in its clinical trial phase, but the incidence of adverse reactions occurring infrequently is likely to emerge only after extensive clinical use. Problems in the investigation and assessment of reports of adverse reactions which occur infrequently are reviewed. It is important that case reports be complete and include details of the batch number and manufacturer of the incriminated vaccine, and of its storage and administration. The assessment of reports of adverse reactions, which are similar in nature to those occurring in equivalent unvaccinated populations, presents special problems and may require case control studies. As new types of vaccines are developed it will be necessary to improve systems which monitor the occurrence of adverse reactions which occur infrequently and those which bear a distant time relationship to immunisation.

Clinical Trials as Topic↗