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Biomedical subjects

J Sutton

Publications and source records attributed to J Sutton.

At least 19 recordsLinked to original sources

Reformulation and drop size of apraclonidine hydrochloride.

We performed a prospective, double-masked, placebo-controlled, six-period, cross-over study in which normal subjects were randomly assigned to treatment and compared three different formulations of apraclonidine hydrochloride (the present commercially available formulation, and formulations with hydroxypropylmethylcellulose or lysolecithin). We also evaluated the efficacy of a 16-microliters and 30-microliters drop size. The magnitude and duration of decrease in intraocular pressure was comparable for all formulations. Most subjects tolerated all formulations well with only a few reporting any side effects. The best-tolerated formulation was 0.5% apraclonidine hydrochloride delivered with a 16-microliters drop size. Dry mouth developed frequently with the commercially available 1% apraclonidine solution. Blurred vision complicated the use of the formulation containing hydroxypropylmethylcellulose. Both dry mouth (P less than .05) and blurred vision (P = .004) were statistically significant side effects.

Adrenergic alpha-Agonists

Genetic modulation of antigen presentation by HLA-B27 molecules.

In studies of antigenic peptide presentation, we have found a healthy volunteer whose lymphoblastoid cells were unable to present three different virus-derived epitopes to cytotoxic T lymphocytes (CTL) despite expressing the correct restricting HLA-B27 molecules on the cell surface. B cell lines were established from other members of the donor's family, including individuals suffering from ankylosing spondylitis and related diseases, and were tested for their ability to function as target cells in the same assay. None of the eight B cell lines that expressed HLA-B27 presented a known peptide epitope to CTL. However, cells from a family member that expressed HLA-B8 could present an epitope peptide restricted by that molecule. The B27 molecule in this family proved to be the B2702 subtype on isoelectric focusing gels, appearing in exactly the same position as B2702 from other cell lines that did present the peptide. To exclude mutations resulting in noncharged amino acid substitutions, cDNA coding for B2702 was cloned from the proband's cell line and sequenced. No coding changes were found. The cloned cDNA was transfected into HLA-A- and B-negative HMy/C1R cells, and the B2702 molecules generated in this environment rendered these cells, after incubation with peptide, susceptible to lysis by peptide-specific CTL. These data are compatible with the presence of a factor(s), possibly HLA linked, interfering with antigen presentation by otherwise normal B2702 molecules in this family.

Antigen-Presenting Cells

Exertion-induced heat exhaustion. An often overlooked diagnosis.

Exertion-induced heat exhaustion is a potentially lethal condition. The earliest signs include unsteady gait and confusion. Recording of rectal temperature is essential. Skin colour, blood pressure and heart rate are not reliable diagnostic signs. The mainstays of therapy are rapid rehydration and cooling. Prompt diagnosis and rapid effective therapy will minimise the risk of death.

Adult

A comparison of the efficacy and tolerability of controlled-release carbamazepine with conventional carbamazepine.

We compared the efficacy and tolerability of controlled-release carbamazepine (CBZ-CR) with conventional carbamazepine (CBZ) in 131 epileptic patients (both men and women, ages 6-65 years) in an open, multicentre, cross-over trial. Patients entered into the trial were previously on CBZ monotherapy or polytherapy. During the first 4 weeks, patients were treated with equivalent daily doses of CBZ and then switched to CBZ-CR for the subsequent 4 weeks. The majority of patients were switched to the more convenient b.i.d. dosing schedule of the controlled-release (CR) preparation without a detrimental effect on seizure frequency or adverse effects. In 44/131 (34%) of patients, the switch to CBZ-CR was accompanied by an improvement in tolerability, primarily due to a reduction in peak-dependent CNS side-effects such as tiredness, double or blurred vision, dizziness and ataxia. At the end of the study, investigators preferred CBZ-CR for 76% of their patients and 70% of the patients preferred CBZ-CR.

Adolescent

The electrocardiogram at rest and exercise during a simulated ascent of Mt. Everest (Operation Everest II).

To evaluate the effect of extreme altitude on cardiac function in normal young men, electrocardiograms were recorded at rest and during maximal exercise at several simulated altitudes up to the equivalent of the summit of Mt. Everest (240 torr or 8,848 m). The subjects spent 40 days in a hypobaric chamber as the pressure was gradually reduced to simulate an ascent. Changes in the resting electrocardiogram were evident at 483 torr (3,660 m) and were more marked at 282 torr (7,620 m) and 240 torr (8,848 m). They consisted of an increase in resting heart rate from 63 +/- 5 to a maximum of 89 +/- 8 beats/min; increase in P-wave amplitude in inferior leads; right-axis shift in the frontal plane; increased S/R ratio in the left precordial leads; and increased T negativity in V1 and V2. No significant arrhythmias or conduction defects were observed. Most changes reverted to normal within 12 hours of return to sea level, with the exception of the frontal-plane axis and T-wave alterations. Maximal cycle ergometer exercise at 282 torr (7,620 m) and 240 torr (8,848 m) resulted in a heart rate of 138 +/- 7 and 119 +/- 6 beats/min at the 2 altitudes, respectively. No ST depression or T-wave changes suggestive of ischemia occurred despite a mean arterial oxygen saturation of 49% and a mean pH of 8 during peak exercise. Occasional ventricular premature beats were observed during exercise in 2 subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Ultrastructure of oocyte migration through the mouse ovarian surface epithelium during neonatal development.

Previous studies using light microscopy have described the presence of oocytes within the ovarian surface epithelium (OSE) of the neonate ovary and their subsequent release into the periovarian space. The ultrastructural examination and quantitative estimate of oocyte migration through the OSE is described in this study. The surface of the mouse ovary is covered by a simple squamous to simple cuboidal epithelium resting on a distinct basal lamina. Healthy, non-atretic primordial follicles located in the periphery of the ovarian cortex interact with the OSE. Oocytes within the primordial follicles are large (50-70 microns), spherical cells surrounded by a single layer of squamous granulosa cells. Migratory oocytes initially display a ruffled border and extend pseudopodia-like cellular extensions towards the OSE. These processes subsequently compromise the basal lamina of the OSE and extend between the epithelial cells. Granulosa cells retract as junctional complexes between them and the oocyte are no longer observed. The oocyte migrates between the OSE cells and passes into the periovarian space without the loss of either OSE or granulosa cells. The rate of oocyte migration reaches a peak during the first week of neonatal development and then gradually diminishes until by day 28 of development no oocyte migration was observed.

Animals

Extraction of DNA from exfoliative cytology specimens and its suitability for analysis by the polymerase chain reaction.

The extraction of DNA from archival exfoliative cytology samples would allow the molecular biological analysis of this readily available material using the polymerase chain reaction (PCR). We have quantitatively and qualitatively studied the extraction of DNA from a variety of cytological preparations. For both fresh and archival cervical smears, overnight incubation with proteinase K produces high yields of high molecular weight DNA, but simply boiling the samples produces DNA suitable for PCR amplification of a single copy gene. Increasing the proteinase K incubation to several days allows the extraction of DNA from fixed and stained archival cytology slides from a variety of sites. The extracted DNA was again suitable for PCR analysis. Fresh and archival cytological material can be utilized for molecular biological study of disease processes using PCR. Archival cytological material is probably the best source of DNA and RNA after stored frozen tissue.

DNA

Transient production and secretion of human transforming growth factor TGF-beta 2.

Transient transfection of simian COS cells with a recombinant plasmid encoding the human transforming growth factor TGF-beta 2 precursor protein results in the production of a latent, biologically inactive protein. Upon acidification, recombinant TGF-beta 2 exhibits full biological activity, including inhibition of mink lung epithelial cell growth, stimulation of anchorage-independent growth of murine embryonic fibroblasts, and competition for TGF-beta receptor binding. Further analysis of conditioned media with antiserum to either a pro- [amino acid (aa) residues 1-220] or mature [aa 297-414] peptide of the TGF-beta 2 precursor suggests that TGF-beta 2, similar to TGF-beta 1 production in Chinese hamster ovary cells [Gentry et al., Mol. Cell. Biol. 7 (1987) 3418-3427], is initially synthesized as a larger precursor protein which is proteolytically cleaved to yield the mature 112-aa transforming growth factor.

Animals

Morphometric diagnosis of serous effusions: refinement of differences between benign and malignant cases by use of outlying values and larger sample size.

Fifty cytologically malignant, five suspicious, and 27 cytologically benign serous effusions were assessed morphometrically for differences in mean and outlying nuclear and cytoplasmic variables. Significant differences were found between benign and malignant specimens for all nuclear morphometric variables measured, the most significant being largest nuclear area and diameter. No significant differences were found for cytoplasmic size variables. Although measurement of outlying values in serous effusions enhanced the difference between benign and malignant cell populations, it was of insufficient sensitivity or specificity to be of clinical diagnostic use. Increasing the sample size improved test performance but would be tedious to perform manually.

Ascitic Fluid

Ayre v Aylesbury cervical spatulas.

A single blind crossover study compared the traditional Ayre spatula with the new Aylesbury spatula. The study group consisted of all women attending the department of genitourinary medicine during a 16 month period. The same incidence (3.6%) of dyskaryotic smears was found using the Ayre spatula (74/2077) as the Aylesbury spatula (72/2003). The incidence of smears with endocervical cells, however, was significantly greater using the Aylesbury (33.4%) than the Ayre (20.4%) spatulas, despite there being no difference in the incidence of smears with epithelial abnormalities. Quantitative studies thus showed that the Aylesbury gave no more accurate results than the Ayre spatula.

Adolescent

Operation Everest II: muscle energetics during maximal exhaustive exercise.

To investigate the metabolic basis for the reduction in peak blood lactate concentration that occurs with maximal exercise after acclimatization to altitude, eight male subjects [maximal O2 uptake of 51.2 +/- 3.0 (SE) ml.kg-1.min-1] were acclimated to progressive hypobaria over a 40-day period. Before decompression (SL-1), at 380 and 282 Torr, and on return to sea level (SL-2) the subjects performed progressive cycle exercise to exhaustion. Analysis of muscle samples obtained from the vastus lateralis before exercise and at exhaustion indicated a pronounced reduction (P less than 0.05) in muscle lactate concentration (mmol/kg dry wt) at 282 Torr (39.2 +/- 11) compared with SL-1 (113 +/- 9.7), 380 Torr (94.6 +/- 18), and SL-2 (92.7 +/- 22). For the other glycolytic intermediates studied (glucose 1-phosphate, glucose 6-phosphate, fructose 6-phosphate, fructose 1,6-bisphosphate, and pyruvate) only the increase in glucose 1-phosphate, glucose 6-phosphate, and fructose 6-phosphate were blunted (P less than 0.05) at 282 Torr. The reduction in muscle glycogen concentration during exercise was similar (P less than 0.05) for all environmental conditions. Although exercise resulted in reductions (P less than 0.05) in ATP and creatine phosphate averaging 30 and 51%, respectively, the magnitude of the change was not dependent on the degree of hypobaria. Inosine monophosphate was elevated (P less than 0.05) approximately 11-fold with exercise at both SL-1 and SL-2. These findings support the hypothesis that the lower lactate concentration observed at 282 Torr after exhaustive exercise is due to a reduction in anaerobic glycolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate

Operation Everest II: coagulation system during prolonged decompression to 282 Torr.

Thromboembolic phenomena may occur as humans ascend to high altitude. To investigate the role of the coagulation cascade and its inhibitors in these disorders, venous blood was obtained from eight subjects who participated in the Operation Everest II project. Samples were obtained before and 5 min after completion of a progressive incremental exercise test to exhaustion at sea level and atmospheric pressures of 380 (18,000 ft) and 282 Torr (25,000 ft). Plasma was analyzed for the activity or concentration of factors II, V, VII, VIII complex, IX-XIII, prekallikrein, high-molecular-weight kininogen, fibrinogen, antithrombin III, alpha 2-macroglobulin, alpha 2-antiplasmin, C1-esterase inhibitor, alpha 1-antitrypsin, and protein C. Prolonged exposure to simulated high altitude did not alter the concentration of any of the coagulation factors or inhibitors. Exercise increased the circulating concentrations of the factor VIII complex at sea level, 380, and 282 Torr. However, the increment was less at the simulated high altitudes. The increase in the factor VIII complex was inversely related to arterial O2 saturation and directly related to the work load achieved and blood pH and plasma lactate concentrations. These studies suggest that the gradual development of marked chronic hypoxia does not affect the coagulation cascade.

Adult

A morphometric study of submandibular salivary gland changes in streptozotocin-induced diabetic rats.

The morphology of the glands in 9 male rats was studied after 3 months of streptozotocin-induced diabetes mellitus and compared with that of 9 control rats and 6 streptozotocin-treated, non-diabetic rats which served as controls for any effect of streptozotocin not due to diabetes mellitus. In the diabetic group, mean salivary-gland weight and volume was reduced. There was an increase in the ratio of mean volume to total gland volume for seromucous acini (p less than 0.01), intra-lobular striated ducts (p less than 0.001), fat (p less than 0.001) and blood vessels (p less than 0.01), and a decrease in both granular duct (p less than 0.001) and intercalated duct (p less than 0.01) volume ratios. There was a marked reduction in the total length of granular ducts (p less than 0.001) and an increase in the length of striated ducts (p less than 0.001). Measurements from the streptozotocin-treated, non-diabetic group did not differ significantly from those of controls. These effects may be attributable to failure of growth and chronic sodium depletion.

Animals

Measurement of postoperative pericardial pressure in man.

Pericardial pressure was measured in 18 patients undergoing cardiopulmonary bypass for up to 10 days using a solid state transducer. Mean and phasic pericardial pressure wave forms were similar to those reported in animals. A wide range of mean pressure from 0 to 30 mmHg was recorded, and values of up to 20 mmHg were observed in patients whose postoperative clinical course was uncomplicated. Fluctuations in pericardial pressure during spontaneous and artificial respiration were small, suggesting that concomitant left ventricular diastolic pressure changes were mainly the result of alterations in diastolic filling. Relative ventricular and pericardial distensibilities were estimated from the ratio of the slopes of diastolic pressure with time, which showed that up to 25 per cent of left ventricular diastolic pressure was supported by the pericardium and 75 per cent by the myocardium. Measurement of pericardial pressure had clinical value in 2 patients in confirming and excluding the presence of pericardial tamponade.

Adolescent