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Biomedical subjects

R McGuinness

Publications and source records attributed to R McGuinness.

30 records · Page 2Linked to original sources
PubMed1980

The Prince of Wales Hospital prospective aphakic macular oedema study.

A two year study of one hundred and forty five cataract extractions showed a 38% incidence of post operative macular oedema. The leak had resolved in most cases by six months and the only factor of significance in the production of the oedema was preoperative hypertension. The likelihood of obtaining 6/6 vision postoperatively was much lessened in the presence of macular oedema.

Adult↗
PubMed1980

Atrax robustus envenomation.

Two patients who developed massive pulmonary oedema, profound vasoconstriction and hypertension followed by hypotension after Atrax Robustus envenomation are described. The pulmonary oedema is due to increased pulmonary capillary membrane permeability which may be due to neurogenic or toxic causes. Use of artificial ventilation with high level PEEP, isoprenaline and high dose steroids allowed support of the patients during volume replacement with albumin. When the circulation was stable and airway frothing ceased, conventional dehydration therapy further improved lung function. Both patients were discharged well.

Adult↗
PubMedDate not supplied

Large-scale manufacturing of safe and efficient retrovirus packaging lines for use in immunotherapy protocols.

BACKGROUND: The use of gene modified T lymphocytes for immunotherapy in a cancer or AIDS clinical trial requires an efficient, safe ex vivo method for modification of these cells at manufacturing scale. Since retroviruses have been shown to be a moderately effective means of stably integrating therapeutic genes into T lymphocytes, we wanted to create packaging and producer cell lines that would produce replication competent retrovirus (RCR)-free supernatants, at large scale (> 200 l), and transduce with high efficiency. METHODS: cDNA expression plasmids containing only coding sequences for gagpol or env were built and sequentially transfected into human 293 cells. Packaging and producer clones were characterized for stability, titer and RCR. A producer clone delivering chimeric immune receptors was scaled-up and supernatants used to transduce patient T lymphocytes for clinical studies. PCR and RT-PCR assays were utilized to evaluate the transmission of HERV-H sequences. Relative infectivity of producer clones pseudotyped with different envelopes was determined by transduction and RT assays. RESULTS: RCR-free, human 293 split-genome packaging lines, pseudotyped with amphotropic, xenotropic, or 10A1 envelopes, were created. A CC49 zeta producer clone was scaled-up to 5 x 54 l lots and supernatants used to safely and efficiently transduce patient T lymphocytes with minimal ex vivo manipulation. While 293 cells express HERV-H mRNA, the transmission frequency in our packaging clones was less than 1 HERV-H sequence per 5 x 10(5) proviral integrations. Additionally, 10A1 and xenotropic packaging lines had higher infectivities than the amphotropic clone. CONCLUSION: These packaging lines represent the safest configuration for the large-scale production of retroviral vectors, and are capable of producing high titer, RCR-free retroviral vector for large scale clinical use. While all three clones efficiently transduce human T lymphocytes, the 10A1 clone has the highest infectivity. These packaging cell lines will be valuable for use in human gene therapy protocols.

Animals↗