Biomedical subjects
Publications and source records attributed to B Horsburgh.
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Clinical resistance to antiviral drugs requires that a virus evade drug therapy yet retain pathogenicity. Thymidine kinase (TK)-negative mutants of herpes simplex virus are resistant to the drug, acyclovir, but are attenuated for pathogenicity in animal models. However, numerous cases of clinical resistance to acyclovir have been associated with viruses that were reported to express no TK activity. We studied an acyclovir-resistant clinical mutant that contains a single-base insertion in its tk gene, predicting the synthesis of a truncated TK polypeptide with no TK activity. Nevertheless, the mutant retained some TK activity and the ability to reactivate from latent infections of mouse trigeminal ganglia. The mutant expressed both the predicted truncated polypeptide and a low level of a polypeptide that comigrated with full-length TK on polyacrylamide gels and reacted with anti-TK antiserum, providing evidence for a frameshifting mechanism. In vitro transcription and translation of mutant tk genes, including constructs in which reporter epitopes could be expressed only if frameshifting occurred, also gave rise to truncated and full-length polypeptides. Reverse transcriptase-polymerase chain reaction analysis coupled with open reading frame cloning failed to detect alterations in tk transcripts that could account for the synthesis of full-length polypeptide. Thus, synthesis of full-length TK was due to an unusual net +1 frameshift during translation, a phenomenon hitherto confined in eukaryotic cells to certain RNA viruses and retrotransposons. Utilization of cellular frameshifting mechanisms may permit an otherwise TK-negative virus to exhibit clinical acyclovir resistance.
Two cases of typically appearing crystalline keratopathy both grew an alpha haemolytic streptococcus and had many of the features common to other cases. In one case, the use of topical and systemic antibiotics alone resulted in resolution of the disease, while in the second case even after corneal transplantation, a recurrence occurred which required further long-term antibiotics plus a repeat transplant.
This paper reviews the current status of our computer model for the management of strabismus and its future direction. Vector analysis was first used in the 1950s for the assessment of strabismus. Robinson's model was the first computer simulation of ocular motility. Using physiological principles and anatomical approximations, Robinson's model sought to predict the strabismic pattern to be expected from a given injury. The Kault/Stark 'reverse' model works in the opposite direction, to first simulate the given strabismic pattern and then advise the surgery required to restore orthophoria. The surgeon is able to 'trial' various operations and compare the expected postoperative results. An automated system is currently being developed to ease the difficulty in measuring the position of the eyes in all nine positions of gaze. This paper includes three illustrative case reports.
A 44-year-old woman with proven Acanthamoeba keratitis was successfully treated medically with resultant 6/9 vision. During the treatment, repeated attempts to titrate the patient off topical corticosteroids resulted in recurrent flare-up of inflammatory keratitis from which Acanthamoeba could not be recultured. It is suggested that steroid administration during the course of Acanthamoeba keratitis may need to be withdrawn extremely slowly to avoid the recurrence of what appears to be an immunological corneal reaction.