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Biomedical subjects

L Lancaster

Publications and source records attributed to L Lancaster.

At least 19 recordsLinked to original sources

The location of protein S8 and surrounding elements of 16S rRNA in the 70S ribosome from combined use of directed hydroxyl radical probing and X-ray crystallography.

Ribosomal protein S8, which is essential for the assembly of the central domain of 16S rRNA, is one of the most thoroughly studied RNA-binding proteins. To map its surrounding RNA in the ribosome, we carried out directed hydroxyl radical probing of 16S rRNA using Fe(II) tethered to nine different positions on the surface of protein S8 in 70S ribosomes. Hydroxyl radical-induced cleavage was observed near the classical S8-binding site in the 620 stem, and flanking the other S8-footprinted regions of the central domain at the three-helix junction near position 650 and the 825 and 860 stems. In addition, cleavage near the 5' terminus of 16S rRNA, in the 300 region of its 5' domain, and in the 1070 region of its 3'-major domain provide information about the proximity to S8 of RNA elements not directly involved in its binding. These data, along with previous footprinting and crosslinking results, allowed positioning of protein S8 and its surrounding RNA elements in a 7.8-A map of the Thermus thermophilus 70S ribosome. The resulting model is in close agreement with the extensive body of data from previous studies using protein-protein and protein-RNA crosslinking, chemical and enzymatic footprinting, and genetics.

Bacterial Proteins↗

Characterization of functionally active subribosomal particles from Thermus aquaticus.

Peptidyl transferase activity of Thermus aquaticus ribosomes is resistant to the removal of a significant number of ribosomal proteins by protease digestion, SDS, and phenol extraction. To define the upper limit for the number of macromolecular components required for peptidyl transferase, particles obtained by extraction of T. aquaticus large ribosomal subunits were isolated and their RNA and protein composition was characterized. Active subribosomal particles contained both 23S and 5S rRNA associated with notable amounts of eight ribosomal proteins. N-terminal sequencing of the proteins identified them as L2, L3, L13, L15, L17, L18, L21, and L22. Ribosomal protein L4, which previously was thought to be essential for the reconstitution of particles active in peptide bond formation, was not found. These findings, together with the results of previous reconstitution experiments, reduce the number of possible essential macromolecular components of the peptidyl transferase center to 23S rRNA and ribosomal proteins L2 and L3. Complete removal of ribosomal proteins from T. aquaticus rRNA resulted in loss of tertiary folding of the particles and inactivation of peptidyl transferase. The accessibility of proteins in active subribosomal particles to proteinase hydrolysis was increased significantly after RNase treatment. These results and the observation that 50S ribosomal subunits exhibited much higher resistance to SDS extraction than 30S subunits are compatible with a proposed structural organization of the 50S subunit involving an RNA "cage" surrounding a core of a subset of ribosomal proteins.

Peptidyl Transferases↗

Radiographic findings after pectus excavatum repair.

Postoperative radiographic changes after pectus repair have not previously been described. We reviewed the chest radiographs of 65 children who underwent surgical repair of pectus excavatum between early 1985 and mid-1992. After operation, 64 children showed atelectasis, 38 had pleural effusions, 30 showed a congestion or edema pattern, 12 had pneumothorax, 21 showed fixation strut tilt or rotation, and 4 had pneumomediastinum. Despite the sometimes worrying radiographic appearance, these children uniformly did well clinically.

Adolescent↗

A study to compare ibuprofen effervescent granules with ibuprofen tablets in the treatment of acute dental pain.

PURPOSE OF STUDY: To compare both the speed of onset and efficacy of the analgesia produced by the effervescent granule formulation with that produced by the conventional-release tablet formulation of ibuprofen in patients suffering acute dental pain and to record the incidence and severity of any adverse events. POPULATION STUDIED: Dental out-patients of either sex and over 16 years of age requiring surgical removal of unilateral or bilateral lower third molar teeth under general anaesthesia as day cases. METHODS: A total of 50 patients received the effervescent granules formulation of ibuprofen 600 mg (Brufen Granules) as study treatment and 50 received the 600 mg tablet formulation in this investigator-blind, parallel-group multiple-dose study. Surgery was performed under general anaesthesia by one or two dental surgeons. Patients received either one sachet of ibuprofen granules or one tablet of ibuprofen at six-hourly intervals for up to 24 hours once post-operative pain became moderate to severe. FINDINGS: Both treatments were shown to be efficacious in treating post-operative dental pain. The granules were found to give significantly better pain relief in the first 30 minutes following the first dose. This may be owing to a more rapid absorption from the granules formulation in these patients and/or a local action of ibuprofen in solution in the mouth. CONCLUSION: The effervescent soluble form of ibuprofen (Brufen Granules) is preferable to the conventional tablet form in managing the immediate dental pain experienced post-operatively by most patients because of its faster onset of action.

Acute Disease↗

The impact of histological review on clinical management of testicular cancer.

Accurate histological diagnosis and staging are critically important in determining the optimal management of patients with testicular cancer. We have assessed the importance of histological review of "outside" pathology reports from 87 patients referred to the Urological Cancer Research Unit. In 28 patients (32%), the reviewed pathology report differed from the outside report. In 10 of these patients (11%), the pathology review resulted in a change of treatment or prognosis from that which would have obtained in the absence of such histological review. Pathology review at a major cancer centre with a subspecialist interest in tumour pathology and a large experience in the management of germ cell malignancy is an essential first step in the treatment of testicular cancer.

Adult↗

Sodium MRI with coated magnetite: measurement of extravascular lung water in rats.

This study was done to see if signal intensity in sodium images of edematous rat lungs made after iv administration of a negative intravascular contrast agent could serve as a measure of the edema fluid present. First, a method to produce a stable condition of hydrostatic pulmonary edema was developed and verified by CT. Second, dose-response curves for coated magnetite preparations were constructed by giving edematous rats varied doses of these preparations and measuring signal intensity changes of various organs by sodium MRI in a 31-cm-bore 1.9-T magnet. Third, rats were given varied levels of pulmonary edema followed by a constant dose of coated magnetite to eliminate the plasma sodium signal. Finally, coated magnetite particles of two sizes were administered to rats, and the differences in effects on signal from various organs were measured. Signal intensity of the lungs after magnetite correlated (r = 0.86) with extravascular lung water measured gravimetrically, suggesting that sodium MRI may be useful for measuring pulmonary edema fluid. Smaller particles appear to remain in the blood longer than larger particles.

Animals↗

The effect of coronary artery lesions on the relationship between coronary perfusion pressure and myocardial blood flow during cardiopulmonary resuscitation in pigs.

In subjects without coronary disease, coronary perfusion pressure generated with closed-chest cardiopulmonary resuscitation (CPR) bears a direct relationship to myocardial blood flow. The effect of coronary lesions on this relationship was studied in an experimental porcine model not requiring thoracotomy. Coronary stenoses (a 50% reduction in coronary cross-sectional area) or total coronary occlusions were created by percutaneous, transarterial catheter placement of a Teflon cylinder in the left anterior descending artery of 21 swine (30 to 60 kg). Coronary perfusion pressure, defined as the aortic diastolic pressure minus right atrial diastolic pressure, was correlated with myocardial blood flow measured with nonradioactive, colored microspheres during external chest compression CPR. Complete occlusion of the left anterior coronary artery resulted in essentially no CPR-generated blood flow to the anterior myocardium distal to the site of occlusion. Coronary perfusion pressure showed a positive correlation with myocardial blood flow above the area of occlusion (r = 0.783; p less than 0.01) but did not correlate with myocardial blood flow below the occlusion site (r = 0.239). In the presence of a patent coronary artery stenosis, coronary perfusion pressure correlated with myocardial blood flow both above (r = 0.841; p less than 0.001) and below (r = 0.508; p less than 0.05) the stenosis. During closed-chest CPR producing coronary perfusion pressures between 30 and 60 mm Hg, anterior myocardial blood flow was 109 +/- 16 ml/min/100 gm above a patent stenosis and 66 +/- 13 ml/min/100 gm below the stenosis (p less than 0.005). Over a wide range of coronary perfusion pressures, myocardial blood flow below a coronary lesion was significantly less than that above the lesion. Coronary occlusions and stenoses can substantially affect the amount of CPR-generated coronary perfusion pressure needed to produce distal myocardial blood flow.

Animals↗

System identifies problems of hospital department.

Identifying and quantifying problems within and outside a hospital business unit is essential if quality improvement is to be successful. In the following article, the author describes how to establish a system in which those problems can be identified and dealt with by the managers and staff of any business unit in the hospital.

Cost-Benefit Analysis↗

An open multiple dose study of Optrex Eye Lotion in eye irritation due to hayfever.

Twenty-four patients consulting their general practitioner with eye irritation due to hayfever entered a seven-day open, multiple dose study of a newly formulated Optrex Eye Lotion. Patients self-administered Optrex by irrigation into their left eye three times daily for seven days, with an option to use the same preparation in their right eye if they thought this to be of benefit. Assessment was by means of daily diary cards completed by the patient each evening for the seven-day period. Following the first instillation, the treated eye felt significantly better at 20 seconds and at four minutes when compared with the untreated eye. Differences between the eyes for degree of redness, comfort and clearness of vision were not significant, but 15 patients (63 per cent) optionally used Optrex in their right eye. Seventeen patients (71 per cent) reported that they derived overall benefit from the use of Optrex Eye Lotion during the study period. Two patients reported side effects during the study but, in each case, the investigator did not consider the event to be therapy related. One patient withdrew on Day 7 of the trial due to worsening of their allergic conjunctivitis. It can be concluded that some subjective benefit was gained by the majority of patients in that a considerable number of them chose to treat both eyes for the duration of the study.

Administration, Topical↗

Serial changes in left ventricular relaxation and chamber stiffness after large myocardial infarction in rats.

To determine the time course of changes in left ventricular diastolic properties after a large myocardial infarction, we serially measured left ventricular relaxation, chamber stiffness, and the ratio of left ventricular cavity to wall volume (V/VW) after coronary artery ligation in rats. Left ventricular relaxation was measured during the occlusion and then both relaxation and chamber stiffness were measured at 3 hr, 24 hr, and 3, 5, and more than 22 days after infarction. Left ventricular pressures and left ventricular dP/dt were recorded with micromanometer-tipped catheters. Left ventricular relaxation was measured by computer digitization of the left ventricular pressure tracings and averaged over 100 to 150 cardiac cycles. Five chamber stiffness constants were calculated from pressure-volume curves that were obtained ex vivo. We found ventricular relaxation prolonged for the first hour after coronary occlusion; relaxation was maximally prolonged at 10 to 15 min after onset of occlusion. After 1 hr relaxation returned to normal. However, by 5 days ventricular relaxation was again prolonged. Left ventricular stiffness constants were increased at 3 and 24 hr, resulting in a shift of the left ventricular pressure-volume relation to the left. At 3 days after coronary artery ligation, all stiffness constants and the pressure-volume relation returned to normal. At more than 22 days the pressure-volume relation was shifted to the right and the stiffness constant for low filling pressures was decreased. V/VW was significantly decreased from 0.603 +/- 0.021 at 3 and 24 hr to 0.379 +/- 0.024 and 0.362 +/- 0.032, respectively. V/VW was significantly increased at more than 22 days (0.921 +/- 0.094).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Right ventricular function at rest and during exercise in aortic and mitral valve disease.

Right ventricular function at rest and during exercise was examined in a group of patients with symptomatic aortic or mitral valve disease, or both. The right ventricular ejection fraction was less than 45% in 22 of 36 patients at rest and in 12 of 17 subjects at symptom-limited, supine bicycle exercise. The right ventricular ejection fraction failed to increase more than 5% with exercise in 17 of 17 patients. The central venous pressure was greater than 5 mm Hg in 18 of 36 patients at rest and in 13 of 17 patients at maximal exercise. There was a significant inverse relation between rest right ventricular ejection fraction and mean pulmonary artery pressure (r = -0.47, p less than 0.05) and between rest right ventricular ejection fraction and mean central venous pressure (r = -0.39, p less than 0.05). There was no significant relation between the exercise values of these variables. In individual patients, the changes in right ventricular ejection fraction and pulmonary artery pressure with graded exercise were nonlinear. It is concluded that right ventricular function is not a simple function of pulmonary artery pressure at rest or during exercise in aortic and mitral valve disease. Less than one-quarter of the variation in right ventricular ejection fraction at rest can be explained by the variation in pulmonary artery pressure, and the finding of a normal (greater than 45%) right ventricular ejection fraction does not reliably exclude the possibility of pulmonary hypertension in a patient with valvular heart disease.

Adult↗

Complete heart block after sublingual nitroglycerin.

A 62-year-old man who was under observation following an episode of severe chest pain developed complete heart block and hypotension after receiving sublingual nitroglycerin. The reaction occurred while the patient was receiving an intravenous maintenance infusion of lidocaine but did not occur in response to either nitroglycerin alone or lidocaine alone. There was no evidence of acute cardiac ischemia nor of clinically significant underlying heart disease. Complete heart block after sublingual nitroglycerin in the absence of significant cardiac disease is an exceedingly rare phenomenon.

Administration, Oral↗