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Biomedical subjects

D R Smith

Publications and source records attributed to D R Smith.

At least 271 records · Page 15Linked to original sources

The 10-diopter base-down fixation test for amblyopia: comparison of techniques.

Two techniques for performing the 10-diopter base-down fixation test were used in 44 patients, and the fixation-pattern responses were compared to determine whether they showed any significant differences. The two techniques elicited the same responses in most cases. A comparison of fixation pattern and visual acuity showed that for most of the patients with equal visual acuity or documented amblyopia an accurate diagnosis could be made with the 10-D base-down fixation test. However, for most of the patients with borderline amblyopia the test either overdiagnosed or underdiagnosed the visual status.

Adolescent↗

Medical and surgical treatment of rheumatic mitral and aortic valve disease.

A retrospective study of 196 patients with rheumatic mitral and aortic valve disease seen at a district general hospital was carried out. Patients having surgical intervention for their valvular disease had a better survival at 10 years (81 per cent +/- 7 per cent) compared to those managed medically (56 per cent +/- 8.5 per cent). This superiority was maintained, both for survival and symptomatic improvement, when individual valve lesions were considered.

Actuarial Analysis↗

The temperature control system of the Cobas-Bio centrifugal analyzer.

The temperature control system of the Cobas-Bio centrifugal analyzer (Roche Analytical Instruments, Montclair, NJ) was evaluated using a calibrated thermistor probe and a solution of cresol red in tris buffer as an "optical thermometer" to measure the temperature of the cuvette contents during operation. The instrument accurately achieves a set temperature of 30 degrees C or 37 degrees C, within thermistor readability of 0.13 degrees C, and maintains that temperature within +/- 0.05 to 0.08 degrees C for at least 18 minutes. There is negligible temperature difference between cuvettes in a rotor during operation. After pipetting samples and reagents into the rotor, 1.5 minutes at 30 degrees C and 2 minutes at 37 degrees C are required to bring the cuvette contents within 0.1 degree C of the set temperature. If a second reagent representing 10% of the total volume is added to cuvettes that have been preincubated at the set temperature, up to 1.5 minutes at 30 degrees C and 2 minutes at 37 degrees C are required to reach temperature equilibrium.

Centrifugation↗

Amplification and modification of dihydrofolate reductase in Escherichia coli. Nucleotide sequence of fol genes from mutationally altered plasmids.

Recombinant plasmids carrying the structural gene for Escherichia coli dihydrofolate reductase (fol) were mutagenized in vitro and in vivo and were used to transform a suitable recipient strain. Twenty-three transformants were isolated that were able to grow in the presence of high levels of the folate analog trimethoprim, and, in each strain, the resistance determinant was shown to be carried on the plasmid. Three of the strains produced dihydrofolate reductase with an increased Ki value for trimethoprim. DNA sequence analysis showed that the plasmids in these strains had mutations in fol which altered a conserved region of the polypeptide that forms part of the dihydrofolate-binding site. Two other strains had approximately 3-fold elevated dihydrofolate reductase levels, apparently resulting from plasmid copy number mutations. The remaining 18 strains had dihydrofolate reductase levels that were 10-30 times higher than those of the starting strain. Surprisingly, three of these strains had no discernible changes either in plasmid copy number or in the nucleotide sequence of the plasmid fol gene. Sequence analysis of the plasmids in 12 more of the strains revealed mutations in the promoter region adjacent to the fol gene. Most of these mutations occurred in the conserved sequences known as the Pribnow box and the -35 region and increased the homology of these sequences with the consensus E. coli promoter sequence. Strains carrying these plasmids produced a significant fraction of their total cell protein as wild type dihydrofolate reductase and should therefore be useful as sources of the purified enzyme.

Autoradiography↗

Nucleotide sequence of dihydrofolate reductase genes from trimethoprim-resistant mutants of Escherichia coli. Evidence that dihydrofolate reductase interacts with another essential gene product.

We report the construction of recombinant plasmids containing the dihydrofolate reductase structural gene (fol) from several trimethoprim-resistant mutants of Escherichia coli. Strains carrying some of these plasmids produced approximately 6% of their soluble cell protein as dihydrofolate reductase and are therefore excellent sources of the purified enzyme for inhibitor binding or mechanistic studies. The nucleotide sequence of the fol region from each of the plasmids was determined. A plasmid derived from a Ki mutant which produced a dihydrofolate reductase with lowered affinity for trimethoprim contained a mutation in the structural gene that altered the sequence of the polypeptide in a conserved region which is adjacent to the dihydrofolate binding site. Two other independently-isolated mutants which overproduced dihydrofolate reductase had a mutation in the -35 region of the fol promoter. One of them, strain RS35, was also temperature-sensitive for growth in minimal medium. This phenotype was shown to be the result of an additional mutation in a locus unlinked to fol by P1 transduction. The fol regions from two temperature-independent revertants of strain RS35 were sequenced. One of these had a mutation within the dihydrofolate reductase structural gene which altered some properties of the enzyme. This confirmed some previous enzymological data which suggested that some revertants of strain RS35 had mutations in fol (Sheldon 1977). These results suggest that dihydrofolate reductase interacts physically with some other essential gene product in E. coli.

Base Sequence↗

Clinical durability of the pericardial xenograft valve: ten years experience with mitral replacement.

Data from 366 patients with mitral valve replacement (250 single and 116 multiple) who received pericardial xenografts between 1971 and 1981 were analyzed. Cumulative duration of follow-up was 1,151 patient-years, with a maximum duration of 10.7 years. Actuarial survival at 11 years is 71.6 +/- 14.2%. Pericardial valve failure occurred in 7 patients (0.6 episodes per 100 patient-years). Actuarial freedom from valve failure at 11 years is 90.4 +/- 9.1% for the entire series. Although 275 (75.1%) patients were in chronic atrial fibrillation, anticoagulants were not used in any patient beyond the first 6 postoperative weeks. The incidence of emboli was 0.6% per year. Six episodes occurred following single mitral valve replacement and 1 after multiple valve replacement (5 early and 2 late). The actuarial freedom from embolism in 96.4 +/- 1.5% at 6 and 11 years postoperatively. Valve thrombosis has not been encountered. This analysis has shown a low incidence of valve dysfunction and a very low risk of embolic complications without long-term anticoagulation. The pericardial xenograft is a safe substitute for the mitral valve, with predictable behavior during the first decade of follow-up.

Adolescent↗

Accurate detection of coronary heart disease by new exercise test.

The ability of a new exercise test accurately to detect the presence and severity of coronary heart disease has been examined in 206 patients with anginal pain, including patients on beta blockers or with concomitant cardiac lesions. From recordings of 13 electrocardiographic leads during exercise, the maximal rate of progression of ST segment depression relative to increased in heart rate (maximal ST/HR slope) was obtained and used as an index of myocardial ischaemia. The maximal ST/HR slope and results of coronary arteriography were independently obtained and the two sets of data compared the ranges of the maximal ST/HR slopes in the 38 patients with no significant disease, 49 with single vessel, 75 with double vessel, and 44 patients with triple vessel disease were different from each other and there was no overlap in the data between adjacent groups; there were no false positive, false negative, or indeterminate results. It is concluded that the maximal ST/HR slope can be used reliably to predict the presence of absence and severity of coronary heart disease in individual patients presenting with anginal pain in a hospital population.

Adrenergic beta-Antagonists↗

Spatial localization after strabismus surgery: evidence for inflow.

Strabismics pointed to targets (without sight of the hand) before and again after surgery that altered the position of the deviating eye in its orbit. Patients having this surgery for the first time were able to use proprioceptively derived information about the surgically altered eye position. In contrast, patients who had similar operations, but on muscles that had been operated on one or more times in the past, were apparently deprived of this information. The important afference may be supplied by the tendon organs.

Afferent Pathways↗

Patent ductus arteriosus in infants of low birth weight.

Patent ductus arteriosus was diagnosed in 239 neonates of low birth weight (less than 2500 g) referred to the Hospital for Sick Children in a 21/2-year period. The respiratory distress syndrome was present in 77% of the group and congestive heart failure in 50%. Spontaneous closure of the defect was more frequent in those without congestive heart failure. In 48 patients whose heart failure could not be controlled by other medical therapy indomethacin was given, and in 20 (42%) it was judged successful. Surgical ligation of the ductus was performed at a median age of 30 days in 33 infants who either failed to respond to indomethacin or in whom its use was contraindicated; there were no intraoperative deaths, but 11 (33%) of the infants died 4 days to 6 months after the operation.

Ductus Arteriosus, Patent↗