Biomedical subjects
R K Calverley
Publications and source records attributed to R K Calverley.
Frequency of occurrence of perforated synapses in developing rat neocortex.
The frequency of occurrence of perforated synapses in the molecular layer of rat parietal cortex has been determined using the disector method. Perforated and non-perforated synapses were examined in electron micrographs, all quantitative procedures being carried out on adjacent sections, as required by the disector procedure. The numerical densities of perforated, non-perforated and all synapses were determined at nine ages, ranging from 0.5 to 22 months of age. The frequencies of perforated synapses were subsequently calculated. These ranged from 18.1% at 0.5 months to a peak of 37.2% at 10 months of age, and remained at around 34% up to 19 months. A frequency of 26.7% was found at 22 months of age. The mean projected height of the total perforation increased from 66 nm at 0.5 months to 133 nm at 22 months of age. These results suggest that perforated synapses are present throughout the life-span of the animal, and increase in complexity with increasing age.
Perforated and non-perforated synapses in rat neocortex: three-dimensional reconstructions.
Perforated and non-perforated synapses in the molecular layer of rat parietal cortex have been assessed morphologically and quantitatively using three-dimensional reconstructions of the postsynaptic terminal. Perforated synapses were analyzed at nine ages, ranging from 0.5 to 22 months of age, and non-perforated synapses at three ages--0.5, 12, and 22 months. Examination of the reconstructions shows that perforated synapses increase in size and complexity with increasing age. This increasing complexity is reflected in a break-up of the postsynaptic density, which is punctuated by larger, branched perforations. In the most extreme cases the result is the appearance of isolated islands of postsynaptic density separated by, and also surrounded by, a synaptic contact zone. Spinules are especially prominent at around 12 months of age in perforated synapses, and the overall negative curvature of the young junctions is replaced by positively curved junctions from 4 months onwards. The non-perforated synapses are relatively small and show few changes with increasing age. Using the measurement option in the reconstruction program, the following trends emerged. All parameters of perforated synapses increased in size with increasing age, whereas the corresponding parameters of non-perforated synapses remained relatively unchanged over this age range. In addition, the percentage of the synaptic contact zone surface area occupied by the postsynaptic density decreased with increasing age in perforated synapses, but increased in non-perforated synapses. The total postsynaptic density surface area of non-perforated synapses per unit volume of molecular layer was double that of perforated synapses at 0.5 months, but the situation was reversed at 12 months. This parameter was similar in the 2 populations at 22 months. This suggests that perforated synapses contribute more to the total surface area of the postsynaptic density in mid- to late-adulthood than do non-perforated synapses, despite non-perforated synapses outnumbering perforated by 2-3:1 at these ages. These data provide more specific evidence that perforated and non-perforated synapses constitute separate synaptic populations from early in development, and that perforated synapses are responsible for the maintenance of neuronal postsynaptic density surface area from mid-adulthood onwards.
Perforated synapses and plasticity. A developmental overview.
Against a background of existing models relating perforated synapses to synaptic plasticity, the numerical density and frequency of perforated synapses in rat neocortex have been assessed from 1 d to 22 mo of age using the disector procedure, and changes in their morphology were assessed using 3-D computer reconstructions. The data point toward perforated and nonperforated synapses being separate synaptic populations from early in development, and with perforated synapses playing a part in the maintenance of neuronal postsynaptic density surface area from mid-adulthood onwards. This suggests that they play a crucial role in synaptic plasticity, although its nature may be different from that postulated by most recent workers.
Estimation of the numerical density of synapses in rat neocortex. Comparison of the 'disector' with an 'unfolding' method.
The numerical density of synapses in the molecular layer of the parietal cortex of normal 28-day-old rats has been estimated by using two stereological methods, namely an unfolding technique and the disector method. For the unfolding technique it was assumed that the synapses formed a polydispersed population of disc-shaped particles. The technique also relies upon various assumptions regarding the size, shape and projection of synapses in the plane of section, these assumptions producing a result that is biased to an unknown extent. Such simplifying assumptions are unnecessary for the disector method. The mean +/- S.E.M. numerical density of synapses was found to be 2.16 +/- 0.14 x 10(9)/mm3 using the disector method. This was not significantly different (paired t-test; P less than 0.05) from the value of 2.41 +/- 0.22 x 10(9)/mm3 obtained using the unfolding technique with correction for truncation ('lost caps'). When the unfolding method was used without a correction for lost caps the numerical density was 1.98 +/- 0.10 x 10(9)/mm3, a value also not significantly different from that obtained using the disector method. The mean projected height (Hs) of the synaptic particles was also determined using both procedures; the results were not significantly different. When the variances of the final estimates and the time taken to carry out the procedures described were taken into account, it was estimated that the disector method was about 86% more efficient than the unfolding method with capping correction. Although the unfolding method can give essentially similar values for the numerical density of synapses to those obtained by the disector method, it is biased and much less efficient. It is concluded, therefore, that the disector method is the superior method for the estimation of the number and size of particles such as synapses, particularly when they have complex spatial configurations.
A serial-section study of perforated synapses in rat neocortex.
The morphology of perforated synapses in the molecular layer of rat parietal cortex has been studied in 28-day-old animals. Of the perforated synapses analyzed, 92% were axospinous and of these all had asymmetrical contacts. A spinule was present in 20% of them, and 63% had a negative curvature (concave with respect to the presynaptic terminal) overall. Up to 95% of perforated synapses had one or more negatively-curved segments. The perforated synapses studied were characterized by postsynaptic densities (PSD) with a mean length of 581 nm, compared with 233 nm for non-perforated synapses. A study of over 100 serially sectioned synapses demonstrated that, in perforated synapses, the PSD and perforations often had a highly irregular shape and arrangement, the site of the perforation frequently projected into the presynaptic terminal, and coated evaginations of membrane, or coated vesicles, were sometimes found at the site of a perforation or towards the periphery of perforated PSDs. Preliminary reconstructions of perforated synapses suggest that, for descriptive purposes, three types can be recognized. Criteria are formulated for determining, on the basis of a study of single sections, which non-perforated profiles belong to perforated synapses.
Determination of the numerical density of perforated synapses in rat neocortex.
The numerical density and frequency of perforated synapses in the molecular layer of rat parietal cortex have been determined using 4 procedures in an attempt to overcome problems associated with the size and complex three-dimensional shape of perforated synapses. The following procedures were compared: A, single-section analysis; B, adjacent-section analysis; C, semi-serial-section analysis; and D, complete serial-section analysis. All procedures made use of an unbiased counting rule. Estimates of the numerical density of perforated synapses ranged from 0.06 to 0.27 X 10(9) mm-3, and that of all synapses (non-perforated and perforated) from 1.88 to 2.50 X 10(9) mm-3. The frequency of perforated synapses varied from 4.5 to 18.0%. Procedures B (adjacent-section analysis) and D (complete serial-section analysis), neither of which utilize assumptions regarding the shape of synapses, produced comparable results (numerical density of perforated synapses 0.19-0.27 X 10(9) mm-3, and of all synapses 2.24-2.45 X 10(9) mm-3; frequency of perforated synapses 8.6-10.9%). The frequency of perforated synapses appeared to be underestimated by procedure A (single section analysis; 4.5%) and overestimated by C (semi-serial section analysis; 18%). It is concluded that adjacent-section analysis is the most efficient and effective procedure for determining the numerical density and frequency of complex particles, such as perforated synapses. There is, however, no significant difference in the performance of this procedure compared with that of single-section analysis, for determining the numerical density of synapses in general. Nevertheless, inherent problems of bias within the single-section procedure make the adjacent section method the procedure of choice.
Anesthesia on the Western Front: the Anglo-American experience of World War I.
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Haemodynamic effects of infusions of diisopropyl phenol (ICI 35 868) during nitrous oxide anaesthesia in man.
The haemodynamic effects of diisopropyl phenol in cremophor EL at infusion rates of 50-55 and 100 micrograms kg-1 min-1 in combination with inhalation of 67% nitrous oxide have been studied during spontaneous and controlled ventilation in patients premedicated with morphine and atropine. Under all the conditions studied diisopropyl phenol supplementation of nitrous oxide anaesthesia was associated with a decreased arterial pressure (-20% to -31%) compared with the awake patient, related to a decrease in cardiac output (-27% to 29%) and an increase in systemic vascular resistance (+8% to +30%) during surgery, but to a decrease in cardiac output (-19%) and a decrease in systemic vascular resistance (-17%) during anaesthesia without surgery. Doubling the infusion rate of diisopropyl phenol caused no significant haemodynamic changes during either spontaneous or controlled ventilation. The haemodynamic manifestations of sympathetic nerve activity in response to laryngoscopy and intubation were poorly suppressed by diisopropyl phenol.
St. René: the Patron Saint of Anaesthetists and a Patron Saint of Canada.
René Goupil, the Patron Saint of Anaesthetists, and a Patron Saint of Canada, was born in Angers, France in 1608 and studied surgery. He joined the Jesuits as a donné or volunteer worker in 1640 and served in the then tiny colony of Quebec as one of the first medical workers of Canada. After earning meritorious praise for his skills, he again volunteered to attend the Hurons at Sainte Marie, a mission far beyond the frontiers. René's canoe party was ambushed. He was captured by the Mohawks and endured eight weeks of cruel torture before being killed on September 29, 1642. René was the first of eight North American martyrs whose dedication was recognized by canonization in 1930. St. René was appointed Patron Saint of Anaesthetists in 1951.
Psychological functioning after halothane or enflurane anesthesia.
Halothane and enflurane anesthesia were administered without surgery to young volunteer subjects who were compared with unanesthetized control subjects. All subjects were tested for intellectual function, visual-motor coordination, and personality characteristics, and they were asked to complete a symptom checklist on three occasions: before anesthesia, 2 days after anesthesia, and 2 weeks after anesthesia. Except for slight temporary effects in a few individuals, anesthesia altered neither intellectual or visual-motor measures nor personality characteristics. Although both anesthetics induced a number of symptoms persisting for 2 days after anesthesia, malaise was clearly greater following halothane than enflurane. Halothane was specifically associated with difficulty in remembering things, difficulty in concentrating, faintness or dizziness, and having to do things slowly to do them right. These symptoms were absent at the 2-week test.
Impact of nitrous oxide on the circulation during enflurane anesthesia in man.
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Inorganic fluoride nephrotoxicity: prolonged enflurane and halothane anesthesia in volunteers.
The effects of prolonged enflurane and halothane administration on urine-concentrating ability were determined in volunteers by examining their responses to vasopressin before anesthesia and on days 1 and 5 after anesthesia. A significant decrease in maximum urinary osmolality of 264 +/- 34 mOsm/kg (26 per cent of the preanesthetic value) was present on day 1 after enflurane anesthesia, whereas subjects anesthetized with halothane had a significant increase in maximum urinary osmolality of 120 +/- 44 mOsm/kg. Serum inorganic fluoride level peaked at 33.6 muM and remained above 20 muM for approximately 18 hours. Thus, the threshold level for inorganic fluoride nephrotoxicity is lower than previously suspected.
Enzyme induction by enflurane in man.
Concentrations of 6-beta-hydroxycortisol (6-OHF), a polar metabolite of cortisol formed in the endoplasmic reticulum (microsomes) of the liver, and 17-hydroxycorticosteroids (17-OHCS) were measured in the urines of six healthy adult male volunteers exposed to a mean of 9.6 MAC-hours of enflurane anesthesia as an index of possible enzyme induction. The ratio of 6-OHF to 17-OHCS in 24-hour urine specimens collected five days before anesthesia was compared with the ratio of these metabolites in 24-hour urine specimens collected 16 to 18 hours after anesthesia. The ratio of 6-OHF to 17-OHCS increased markedly in five and decreased slightly in one volunteer following anesthesia. The results indicate that enflurane may cause induction of hepatic microsomal enzymes.
Letter: Peripheral neurectomy in managing problems of flexor spasticity in patients with multiple sclerosis.
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A clinical study of serum magnesium concentrations during anaesthesia and cardiopulmonary bypass.
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The anaesthetic management of pelvic laparoscopy.
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