Biomedical subjects
Publications and source records attributed to T C Brown.
Dorsal nerve of penis block is becoming more widely used for circumcision in infants and children. Various techniques have been described. This paper presents a detailed study of the anatomy involved based on anatomical dissections and radiological studies. Complications and their possible causes are discussed.
A review of the anaesthetic management of children with congenital myotonic dystrophy anaesthetised at the Royal Children's Hospital over the past ten years is presented. Seven children underwent a total of fourteen anaesthetics. Anaesthetic considerations must include the degree of muscle weakness and hypotonia altering muscle relaxant requirements, aspiration risk due to palatopharyngeal dysfunction, and cardiomyopathy. Succinylcholine caused muscle contracture in a patient without clinical myotonia. This drug should be avoided. Although a low threshold to institute postoperative respiratory support must exist when treating neonates and infants, the older children did not clinically exhibit increased sensitivity to respiratory depressant drugs.
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A neodymium:yttrium aluminum garnet (Nd:YAG) laser was used to study effects of applying laser irradiation transendoscopically to the corniculate process of the arytenoid cartilage in horses. Dosimetry was established initially in vitro in 10 corniculate cartilages that were irradiated and examined histologically to determine penetration depths at selected power settings. Eleven horses were given xylazine IV and butorphoral tartrate IV, and their left ventricle and corniculate process were irradiated. Six horses had left laryngeal hemiplegia and were euthanatized and necropsied 14 weeks after laser application and evaluation for upper airway stridor. Endoscopy was performed in the 5 other horses; they were euthanatized and necropsied at selected intervals to characterize the healing process. Healing was by second intention and was complete at 14 weeks. Two horses developed buds of granulation tissue along the laser incision, which resolved after a second laser application. Scar tissue formation resulted in left of midline displacement of the dorsal portion of the right corniculate process. The left ventricle healed without complications and was totally ablated. All horses had inspiratory stridor when exercised 14 weeks after laser irradiation.
The two transition mispairs G/T and A/C are corrected with different efficiencies and specificities in CV-1 African green monkey kidney cells. G/T mispairs are corrected with 99% efficiency and almost always in favor of guanine, while A/C mispairs exhibit a 31% uncorrected sector and are otherwise randomly corrected. The higher correction efficiency and bias for the G/T mispair can be correlated with the substrate specificity of a protein, found in HeLa and CV-1 cell extracts, that binds selectively to oligonucleotide duplexes containing G/T mispairs. No binding can be detected to duplexes containing other mispairs, or to homoduplexes.
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Mismatches arise during recombination, as errors of DNA replication, and from deamination of 5-methylcytosine to thymine. We determined the efficiency and specificity of mismatch correction in simian cells. Analysis of plaques, obtained after transfection with SV40 DNA molecules harboring a single mispair in a defined orientation within the intron of the large T antigen gene, revealed that all types of base/base mispairs were corrected, albeit with different efficiencies and specificities. Heterogeneous mispairs G/T, A/C, C/T, and A/G, corrected with 96%, 78%, 72%, and 39% efficiencies, respectively, tended to be corrected to G/C. Homogeneous mispairs G/C, C/C, A/A, and T/T were corrected with 92%, 66%, 58%, and 39% efficiencies, respectively, and repair bias was influenced by mismatch flanking sequences.
It has been shown previously that fragmentation of target cell DNA is an early event in lysis mediated by cytolytic T lymphocytes (CTL). In this study, we have investigated whether CTL-derived granules that exhibit lytic activity also induce DNA fragmentation in murine target cells. Cytolytic granules isolated from three different alloreactive CTL clones were tested for the induction of DNA fragmentation in P815 and EL4 target cells, by using a Triton X-100-facilitated, radiolabeled DNA release assay. In contrast to the CTL clones from which they were derived, the cytolytic granules did not induce DNA fragmentation. Agarose gel electrophoretic analysis of DNA confirmed the lack of discrete DNA fragments in target cells lysed by CTL-derived granules. Possible explanations for the difference in the ability of CTL and CTL-derived granules to trigger DNA fragmentation are discussed.
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5-Methylcytosine spontaneously deaminates to form thymine, thus generating G/T mispairs in DNA. We investigated the way in which these lesions are addressed in mammalian cells by introducing specific G/T mispairs into the genome of SV40 and determining the fate of the mismatched bases in simian cells. Mispairs were incorporated in 12 bp synthetic duplexes ligated into SV40 DNA between the BstXI and TaqI restriction sites. Analysis of 347 plaques obtained after transfection of this modified DNA indicated that mispairs were corrected in 343 cases (99%), revealing 314 repair events in favor of guanine (90%) and 29 in favor of thymine (8%). Correction in favor of guanine occurred regardless of the orientation of the mispair in DNA and regardless of whether the mispair was in the commonly methylated CpG dinucleotide. These results attest to a specific mismatch repair pathway that restores G/C pairs lost through deamination of 5-methylcytosine residues.
We exposed simian virus 40-infected CV-1 monkey cells to the carcinogen N-acetoxy-acetylaminofluorene and monitored the removal of lesions from cellular DNA and from various regions of viral DNA. Exposure to 5.5 microM 3H-labeled carcinogen produced 20-80 adducts per 10(6) bases in cellular DNA in different experiments. The initial adduct concentration in viral DNA was always approximately half that in cellular DNA. At various times after treatment, cellular and viral DNA, and restriction fragments of viral DNA, were purified and examined for adduct density. Independent of the initial adduct concentration three rates of repair were observed. Cellular DNA was repaired at the lowest rate. Viral DNA was repaired about 50% more rapidly than was cellular DNA isolated from the same carcinogen-treated monolayers. Within the viral DNA a 366-base pair region containing the major nuclease-hypersensitive site was repaired at twice the rate of the rest of the viral genome. This region contains regulatory sequences that govern the initiation of DNA replication and viral gene expression. As reported previously this region was initially modified 1.71 +/- 0.20-fold higher than expected from its guanine content. Selective repair diminished the extent of hypermodification of this region by 6.0 +/- 2.1% per hour, partly compensating for the higher initial level of adducts.
A mathematical model is presented which may be applied to describe and analyse data from microscopic phagocytosis assays. The method has been used to investigate the phagocytosis of opsonized yeast by peripheral blood neutrophils treated with purified recombinant human granulocyte-macrophage colony-stimulating factor (rH GM-CSF) in vitro. Under limiting conditions of serum opsonization, rH GM-CSF decreased the proportion of non-phagocytic cells and increased the mean number of ingested yeast per cell. Stimulation of phagocytosis was dose-dependent and occurred with concentrations of rH GM-CSF in the range 10-320 units/ml. The effect was dependent on a heat-labile component in serum and was not attributable to endotoxin contamination of the preparation.
Integrated electromyographic studies in burned patients, and in normal controls, during the administration of small doses of suxamethonium (0.1 or 0.2 mg kg-1) have shown that the level of paralysis and the duration of paralysis are significantly increased in burn patients and that the effect is greater with larger burns. Repeated studies on patients using these small doses have shown that patients with burns pass through a phase of extreme sensitivity to the effects of suxamethonium, usually sometime between 4 and 12 days after the burn.
The survival of transfected simian virus (SV) 40 DNA is acutely sensitive to damage in a 302-bp regulatory region that governs viral gene expression and the initiation of viral DNA replication. We investigated whether the lethal effect of damage in this region is due to the disruption of gene expression or to the inhibition of DNA replication by comparing the survival of damaged viral DNA in CV-1 and cos-1 African green monkey cells. Viral early sequences integrated into the genomic DNA of cos-1 cells complement the growth of virus with defective early genes and were therefore expected to reverse viral sensitivity to lesions that interfere with early gene expression. Our results indicate that viral sensitivity to damage in the regulatory region is almost completely abolished in cos-1 cells. This finding identifies gene expression rather than the initiation of DNA replication as the major target for lethal damage in that portion of the SV40 genome. Sensitivity to damage in the viral late gene region is the same in CV-1 and cos-1 cells, indicating that cos-1 cells are not merely more proficient in host-cell reactivation. Our results allow us to partition the overall lethal effect of DNA damage into sectors, and to assign each sector to the disruption of a particular genetic function.
Electromyographic studies of the onset of action of tubocurarine or alcuronium were performed on eight occasions in five patients who had liver masses. There was a slow onset of action and an increased dose requirement in those with malignant disease. Normal responses were found in a patient with benign nodular hyperplasia and in another where the malignant tumour was successfully treated with chemotherapy.
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A study in anaesthetised dogs aged 2, 6, 13, 26 and 52 weeks or older was done to determine the dose of IV bupivacaine given by infusion required to produce severe cardiovascular depression as measured by a drop in mean blood pressure to about 25 mmHg or the development of life-threatening dysrrhythmias. Plasma local anaesthetic concentration was analysed at the time of ceasing the infusion. The toxic dose was significantly less in the six-week-old group than younger or older animals. The plasma concentrations associated with toxicity in the groups 13 weeks and younger were significantly lower than in the older dogs. Treatment of the induced toxicity included hyperventilation, adrenaline infusion, bretylium and/or cardioversion. The response to treatment was better in young dogs than adult dogs.