Biomedical subjects
Publications and source records attributed to I J Jackson.
This short communication describes the use of the Carden anaesthetic tube during surgery in and around a tracheostome. The technique, which greatly facilitates access to the operating field, is described along with it's indications and contraindications. We would like to recommend extending the use of the Carden tube to operations around a tracheostome, thereby maximizing surgical access.
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We describe 4-yr experience providing extradural infusion analgesia in a district hospital for treatment of postoperative pain. A total of 770 patients recovering from major surgery were treated on general surgical wards between April 1989 and March 1993. The results of a retrospective audit showed that pain control, assessed with both a visual analogue scale (VAS score (0-10 cm)) and a verbal rating scale (VRS), was good. At rest, more than 80% of patients scored pain as absent or mild (VAS score 0-3) during the first 24 h, with only 4% experiencing severe pain (VAS score 7-10). On movement, 50% of patients had good pain control (VAS score 0-3) while 20% of patients experienced severe pain (VAS score 7-10). Minor complications such as emetic sequelae and pruritus were common; these conditions were mild and rarely required treatment. Hypotension (< 100 mm Hg) occurred in 34% of patients in the first 24 h. Ventilatory frequencies of 8 b.p.m. or less occurred in 2.6% of patients. Four patients (0.52%) developed severe respiratory depression. These patients demonstrated increased sedation but only one had a low ventilatory frequency. Three patients died while receiving extradural infusion analgesia.
Over a period of many years, germ-cell mutagenesis experiments using the mouse specific-locus test have generated numerous radiation- and chemical-induced alleles of the brown (b; Tyrp 1) locus in mouse chromosome 4. We describe here the origin, maintenance and initial molecular characterization of 28 b mutations that are prenatally lethal when homozygous. Each of these mutations is deleted for Tyrp 1 sequences, and each of 25 mutations tested further is deleted for at least one other locus defined by molecular clones previously found to be closely linked to b by interspecific backcross analysis. A panel of DNAs from mice carrying a lethal b mutation and a Mus spretus chromosome 4 was used in the fine structure mapping of these molecularly defined loci. The deletional nature of each of these prenatally lethal mutations is consistent with the hypothesis that the null phenotype at b has an effect only on the quality (color) of eumelanin produced in melanocytes. The resulting deletion map provides a framework on which to build future molecular-genetic and biological analyses of this region of mouse chromosome 4.
The formation of mouse coat color is a relatively complex developmental process that is affected by a large number of mutations, both naturally occurring and induced. The cloning of the genes in which these mutations occur and the elucidation of the mechanisms by which these mutations disrupt the normal pigmentation pattern is leading to an understanding of the way interactions between gene products lead to a final phenotype.
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Forty patients undergoing total abdominal hysterectomy were randomly allocated to receive either 40 micrograms.kg-1 of alfentanil on induction of anaesthesia or 40 micrograms.kg-1 of alfentanil after the skin incision. Postoperative pain relief was provided with morphine from a patient-controlled analgesia system. The amount of morphine consumed in the operating theatre, while in recovery and for the first 24 h postoperatively was recorded. Pain scores were assessed at 24 h using a visual analogue scale. There were no differences found between the two groups for morphine consumption but the 'pre-emptive' group had significantly higher pain scores at rest. We conclude that there is no clinically useful pre-emptive analgesic effect with this dose of alfentanil and that therefore systemic opioid premedication is unlikely to decrease postoperative analgesic requirements through the mechanism of pre-emptive analgesia.
On analysis of 46 Geneticin-resistant (GtR) cell lines, derived by electroporation of mouse embryonic stem (ES) cells with a promoterless neo vector, we observed that in two independently derived cell lines, the vector had integrated into the same locus. The sequence flanking the vector integration site in both cell lines was cloned and sequenced. The vector had integrated into a 3 to 6-bp region in both cell lines. No homology is observed between the integration site sequence and the vector sequence.
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Eight experienced anaesthetists performed a 'cockpit drill', following instructions in the Association of Anaesthetist's checklist, on an anaesthetic machine that had a significant leak (3 l.min-1 at a pressure of 16 kPa). Only one anaesthetist detected the leak and this was by audible means rather than by any of the protocol's set manoeuvres. We demonstrated that a leak of 3 l.min-1 from the flowmeter block resulted in an inspired oxygen concentration of 6% when the anaesthetic machine was used with a minute volume divider ventilator.
The Light mutation (Blt) is a dominant allele of the b-locus on mouse chromosome 4 which causes progressive dilution of coat colour. Melanocytes within the hair follicles of mutant mice develop normally but later degenerate, due to the accumulation of a toxic product, so that the hair becomes lighter with age. Previous studies on W-locus spotting mutants, from which melanocytes are absent, have shown that melanocytes in the stria vascularis of the inner ear are essential for the development and/or maintenance of the endocochlear potential (EP) which is normally around 100 mV. In this study, physiological recordings from the ears of Light mutants were correlated with strial ultrastructure. EPs recorded from all b/b controls and young homozygous and heterozygous mutants (20-22 days old) were normal (77 to 113 mV), but were reduced (19 to 59 mV) in about 30% of ears from older mutants (Blt/Blt and Blt/b). Strial function therefore appears to develop normally but later degenerates in some mutants. This suggests that strial melanocytes are affected by the Light allele and that the continued presence of melanocytes is necessary for strial function. There was no obvious association between the recorded EP value and the ultrastructural appearance of the stria. No structural abnormalities of the stria were noted in control or mutant mice aged 20 days to 4 months including those which had a reduced EP. Strial atrophy was common in old controls and mutants (1-2 years), and appeared to be an age-related process rather than an effect of the Light mutation. Similarly, pigment build-up was common in all strial cells of old mice. However, the accumulations of lipofuscin-like pigment were much larger and more abundant in aged brown non-agouti mice than those observed in old agouti mice, which suggests that this age-related process also has a genetic component.
To assess the impact of introducing spinal anaesthesia for obstetric operative procedures on use of general anaesthesia and quality of regional anaesthesia in a unit with an established epidural service a retrospective analysis of routinely collected data on method of anaesthesia, efficacy, and complications was carried out. Data were collected from 1988 to 1991 on 1670 obstetric patients requiring an operative procedure. The introduction of spinal anaesthesia in 1989 significantly reduced the proportion of operative procedures performed under general anaesthesia, from 60% (234/390) in 1988 to 30% (124/414) in 1991. The decrease was most pronounced for manual removal of the placenta (88%, 48/55 v 9%, 3/34) and emergency caesarean section (67%, 129/193) v 38%, 87/229). Epidural anaesthesia decreased in use most significantly for elective caesarean section (65%, 77/118 v 3% 3/113; x2=139, p<0.0001). The incidence of severe pain and need for conversion to general anaesthesia was significantly less with spinal anaesthesia (0%, 0/207 v 3%, 5/156; p<0.05). Hypotension was not a problem, and the incidence of headache after spinal anaesthetic decreased over the period studied. Introducing spinal anaesthesia therefore reduced the need for general anaesthesia and improved the quality of regional anaesthesia.
The production of melanin pigment in mammals requires tyrosinase, an enzyme which hydroxylates the amino acid tyrosine to DOPA (3,4-dihydroxyphenylalanine), thus allowing the cascade of reactions necessary to synthesize that biopolymer. However, there are other regulatory steps that follow the action of tyrosinase and modulate the quantity and quality of the melanin produced. DOPAchrome tautomerase is one such melanogenic enzyme that isomerizes the pigmented intermediate DOPAchrome to DHICA (5,6-dihydroxyindole-2-carboxylic acid) rather than to DHI (5,6-dihydroxyindole), which would be generated spontaneously. This enzyme thus regulates a switch that controls the proportion of carboxylated subunits in the melanin biopolymer. Efforts to clone the gene for tyrosinase have resulted in the isolation of a family of tyrosinase related genes which have significant homology and encode proteins with similar predicted structural characteristics. Using specific antibodies generated against synthetic peptides encoded by unique areas of several of those proteins, we have immuno-affinity purified them and studied their melanogenic catalytic functions. We now report that TRP-2 (tyrosinase related protein-2), which maps to and is mutated at the slaty locus in mice, encodes a protein with DOPAchrome tautomerase activity.
We have cloned and sequenced mouse cDNAs corresponding to a third member of a family of melanocyte-specific mRNAs, which encode tyrosinase and related proteins. This new member, tyrosinase-related protein-2 (TRP-2), has approximately 40% amino acid identity with the two other proteins in the family and has the same structural features including two copper binding sites, two cysteine-rich regions, a signal peptide and a transmembrane domain. We now show that one of the cysteine-rich regions in this protein family is an 'EGF-like' repeat found in many extracellular and cell surface proteins. The gene encoding TRP-2 maps to mouse chromosome 14, in the region of the coat colour mutation slaty. We show that the TRP-2 of slaty mice has a single amino acid difference from wild-type TRP-2; a substitution of glutamine for arginine in the first copper binding site. TRP-2 is the much sought melanogenic enzyme DOPAchrome tautomerase (DT), which catalyses the conversion of DOPAchrome to 5,6,dihydroxyindole-2-carboxylic acid. Extracts from mice homozygous for the slaty mutation have a 3-fold or more reduction in DT activity, indicating that TRP-2/DT is encoded at the slaty locus, and the missense mutation reduces but does not abolish the enzyme activity.
Light is a dominant mutant allele of the mouse brown locus which results in hairs pigmented only at their tips. The phenotype is due to premature melanocyte death. We have sequenced the tyrosinase-related protein-1 cDNA encoded at this locus from Light mice and found that it contains a single base alteration from wild-type, causing an Arg to Cys change in the protein. To further elucidate the mutant phenotype, we studied the expression of melanocyte specific genes in the skin of Light mice. We have demonstrated premature melanocyte death, but only in pigmented mice, indicating that the cell death is mediated through the inherent cytotoxicity of pigment production.
We have examined postoperative pain in patients allocated randomly to receive extradural bolus diamorphine 3.6 mg, extradural infusion of 0.15% bupivacaine with 0.01% diamorphine or patient-controlled i.v. administration of diamorphine at a maximum rate of 1 mg per 5 min, after total abdominal hysterectomy. Extradural infusion analgesia produced the smallest pain scores from 12 to 24 h after surgery (P < 0.05). More patients in the extradural infusion group were moderately hypoxaemic (SpO2 < 90% > 12 min h-1) after operation, compared with the two other groups (P < 0.05). The group using patient-controlled analgesia received more diamorphine and suffered a greater incidence of emetic sequelae (P < 0.05).