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Biomedical subjects

D Tyrrell

Publications and source records attributed to D Tyrrell.

35 records · Page 2Linked to original sources

The origins of the Common Cold Unit.

In 1941 Harvard University and the American Red Cross provided an epidemiological team and an infectious diseases hospital for Britain. Since 1946 the buildings have been occupied by the Common Cold Unit where research has been carried out into many aspects of the causative viruses and their role in the disease, and also into methods of preventing it. The establishment is to be closed down this year.

Common Cold↗

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. SUBJECTS: 87 Unselected patients with typical acute nasal and upper respiratory symptoms (general practice study), and 84 volunteers aged 18-50 without a history of chronic or allergic diseases. INTERVENTIONS: Subjects breathed from apparatus delivering 40 litres of room air heated to 43 degrees C or 30 degrees C and fully humidified (relative humidity 100%) per minute. End point--Reduction in severity of disease. MEASUREMENTS and main results--Patients recorded their symptoms (general practice study) and observers recorded symptoms and signs, weight of nasal secretions, isolation of virus, and antibody responses in volunteers. Patients treated for 20 minutes at 43 degrees C had in the succeeding days roughly half the score for symptoms of those treated at 30 degrees C. Volunteers treated for 30 minutes on three occasions when they were starting a cold showed an 18% [corrected] reduction in symptoms. Treatment of volunteers for 20 minutes at the onset of the cold and for 10 minutes on succeeding days showed no difference between 43 degrees C and 30 degrees C. CONCLUSIONS: Nasal hyperthermia can improve the course of a common cold and also give immediate relief of symptoms.

Adolescent↗

Detection of human coronavirus 229E in nasal washings using RNA:RNA hybridisation.

A method is described for the detection of human coronavirus 229E (HCV 229E) in nasal washings using RNA:RNA filter hybridisation. Volunteers were inoculated with HCV 229E, and daily nasal washings were collected. These washings were then examined for the presence of viral RNA using a single-stranded RNA probe. Nucleic acid hybridisation is shown to be a sensitive technique for the diagnosis of HCV 229E infections.

Coronaviridae↗

Immunogenicity and pathogenicity of temperature-sensitive modified respiratory syncytial virus in adult volunteers.

Single temperature-sensitive (ts) mutants of a subgroup A strain of respiratory syncytial (RS) virus whose multiplication is restricted at 39 degrees C in MRC-6 cells and double ts mutants that are restricted at 38 degrees C, were obtained following mutagenesis using 5-fluorouracil and acridine-like compounds. Isolation and propagation of the parental RSS-2 strain of RS virus and its derived ts mutants were carried out entirely in MRC-5 human diploid cells. The immunogenicity and disease-producing ability of four of these mutants and the parental unmodified strain have been assessed by intranasal administration into groups of about 20 adult volunteers. The results of these trials indicate that the capacity of the parental RSS-2 strain to produce upper respiratory tract infection in adults was not diminished by limited propagation in MRC-5 cells. The mutants on the other hand were impaired in this respect to varying extents. The double mutant tslB in particular has characteristics that suggest that it may be suitable for further development as a live RS virus vaccine. It retained near normal immunogenicity and replicative ability in the upper respiratory tract, while exhibiting greatly reduced disease-producing potential.

Adult↗

Effects of interferon alpha on performance in man: a preliminary report.

The effects of three doses of interferon alpha (1.5 Mu, 0.5 Mu and 0.1 Mu) on performance were studied. The injection of 1.5 Mu IFN produced symptoms and performance changes which closely resembled those found in volunteers with influenza. Specifically, volunteers were slower at responding when they were uncertain when a target stimulus would appear, but were not impaired on a pursuit tracking task or syntactic reasoning task. The results suggest that interferon-induced changes in CNS function provide a plausible explanation for the selective effects of influenza on performance.

Adult↗

Diurnal variation in the symptoms of colds and influenza.

The present research examined diurnal variation in the severity of symptoms of experimentally-induced colds and influenza. Nasal secretion was greatest in the morning, decreased over the day, and then showed a slight increase in the late evening. Colds did not change the average temperature, nor did they alter the temperature rhythm. Similar, negative results were found with alertness ratings. Influenza B illnesses produced an increase in nasal secretion and systemic effects. The average temperature increased during this illness and subjects reported that they felt more drowsy. Diurnal variation in the severity of local and central symptoms was observed, with nasal secretion and the temperature increase being greatest in the early morning. These results have important implications for the assessment and treatment of the illnesses.

Adult↗

Failure of human fibroblast interferon to protect against rhinovirus infection.

Volunteers were treated with fibroblast interferon or placebo nose drops for four days. On the second day, they received a challenge with rhinovirus type 4. There was no difference in the clinical symptoms or viral shedding between the two groups. The possible reasons for this result are discussed.

Administration, Intranasal↗

Glycolytic enzymes in resting spores and vegetative mycelia of Entomophthora pyriformis.

Specific activities of 14 enzymes of the Embden-Meyerhof-Parnas and pentose phosphate pathways were determined in extracts of resting spores and vegetative mycelia of Entomophthora pyriformis. All these enzymes were detected in mycelial extracts, whereas only nine were detectable in resting spore extracts. Activities of detectable spore enzymes were much lower than those of the corresponding mycelial enzymes with the exception of triosephosphate dehydrogenase, which had higher activity in spore extracts. The enzyme deficiencies noted point to the inability of either pathway to function in dormant spores.

Carbohydrate Epimerases↗

Barrett's esophagus: a surgical disease.

Barrett's metaplasia can develop in patients with gastroesophageal reflux disease (GERD), and metaplasia can evolve into dysplasia and adenocarcinoma. The optimal treatment for Barrett's metaplasia and dysplasia is still being debated. The study reported herein was designed to assess the following: (1) the incidence of Barrett's metaplasia among patients with GERD; (2) the ability of laparoscopic fundoplication to control symptoms in patients with Barrett's metaplasia; (3) the results of esophagectomy in patients with high-grade dysplasia; and (4) the character of endoscopic follow-up programs of patients with Barrett's disease being managed by physicians throughout a large geographic region (northern California). Five-hundred thirty-five patients evaluated between October 1989 and February 1997 at the University of California San Francisco Swallowing Center had a diagnosis of GERD established by upper gastrointestinal series, endoscopy, manometry, and pH monitoring. Thirty-eight symptomatic patients with GERD and Barrett's metaplasia underwent laparoscopic fundoplication. Eleven other consecutive patients with high-grade dysplasia underwent transhiatal esophagectomies. Barrett's metaplasia was present in 72 (13%) of the 535 patients with GERD. The following results were achieved in patients who underwent laparoscopic fundoplication (n = 38): Heartburn resolved in 95% of patients, regurgitation in 93% of patients, and cough in 100% of patients. With regard to transhiatal esophagectomy (n = 11), the average duration of the operation was 339 +/- 89 minutes. The only significant complications were two esophageal anastomotic leaks, both of which resolved without sequelae. Mean hospital stay was 14 +/- 5 days. There were no deaths. The specimens showed high-grade dysplasia in seven patients and invasive adenocarcinoma (undiagnosed preoperatively) in four (36%). These results can be summarized as follows: (1) Barrett's metaplasia was present in 13% of patients with GERD being evaluated at a busy diagnostic center; (2) laparoscopic fundoplication was highly successful in controlling symptoms of GERD in patients with Barrett's metaplasia; (3) in patients with high-grade dysplasia esophagectomy was performed safely (invasive cancer had eluded preoperative endoscopic biopsies in one third of these patients); and (4) even though periodic endoscopic examination of Barrett's disease is universally recommended, this was actually done in fewer than two thirds of patients being managed by a large number of independent physicians in this geographic area.

Adenocarcinoma↗