Current status of asymmetric synthesis.

In the last 30 years the subject of asymmetric synthesis has grown from a little studied academic niche in organic chemistry to an intensely investigated field of commercial importance and heightened general interest. Impressive advances have been made in several areas, notably catalytic asymmetric homogeneous hydrogenation, catalytic asymmetric epoxidation of allyl alcohols and stereochemical control of carbon-carbon bond-forming reactions. Asymmetric synthesis must now be deliberately considered along with other available methods as a practical strategy for the synthesis of any chiral compound.

Effects of uncertainty and target displacement on the latency of express saccades in man.

Saccadic eye movements generated in response to a gap paradigm in which the fixation light spot was extinguished 200 ms prior to presentation of the target light spot showed appreciably shorter latencies than for the overlap paradigm in which the target light spot was presented 200 ms prior to extinction of the fixation light spot. When there was unpredictability in the direction of target presentation, i.e., to the left or right of the fixation light spot, the gap paradigm evoked mainly fast regular saccades of peak latency of 155 ms with relatively few express saccades which were defined as having latencies of less than 120 ms. By contrast, when the target always appeared to the right, a substantial population of express saccades with peak latency 95 ms was now generated. There was also a change in the relationship between saccadic latency and target angular displacement which covered the range 5-35 degrees . With the overlap paradigm and unpredictability of target direction, the latencies of the slow regular saccades increased markedly with target angular displacement. This was not the case with the same target direction when the latency of slow regular, fast regular, and express saccades remained constant with increasing target angular displacement. This indicates for targets appearing in the same hemifield that the ocular motor system operates with shortest latency irrespective of target angular displacement.

Investigations into the absorption of insulin and insulin derivatives from the small intestine of the anaesthetised rat.

Experiments have been undertaken to determine the extent to which cholic acid conjugates of insulin were absorbed from the small intestine of anaesthetised rats by means of the bile salt transporters of the ileum. The measure used to assess the absorption of the cholyl-insulins was the amount of hypoglycaemia following infusion into the small intestine. Control experiments involving infusion of natural insulin into the ileum showed either nil absorption or absorption of a small amount of insulin as indicated by transient dip in the blood glucose concentration. However, when insulin was co-infused with the bile salt taurocholate, this was followed by a marked hypoglycaemic response which was specific to the ileum and did not occur on infusion into the jejunum. When the two cholyl conjugates of insulin were tested viz. B(29)-Lys-cholyl-insulin and B(1)-Phe-cholyl-insulin, both were biologically active as indicated by hypoglycaemic responses on systemic injection, though their potency was about 40% of that of natural insulin. While there was no evidence for the absorption of B(29)-Lys-cholyl-insulin when infused into the ileum, B(1)-Phe-cholyl-insulin did cause a long lasting hypoglycaemic response, indicating that absorption had occurred. Since the hypoglycaemic response was blocked on co-infusion with taurocholate and was absent for infusion of the conjugate into the jejunum, these results were taken as evidence that B(1)-Phe-cholyl-insulin had been taken up by the ileal bile salt transporters. This would indicate that B(1)-Phe-cholyl-insulin is worthy of further investigation for use in an oral insulin formulation.

Relationship between visual field loss and contrast threshold elevation in glaucoma.

BACKGROUND: There is a considerable body of literature which indicates that contrast thresholds for the detection of sinusoidal grating patterns are abnormally high in glaucoma, though just how these elevations are related to the location of visual field loss remains unknown. Our aim, therefore, has been to determine the relationship between contrast threshold elevation and visual field loss in corresponding regions of the peripheral visual field in glaucoma patients. METHODS: Contrast thresholds were measured in arcuate regions of the superior, inferior, nasal and temporal visual field in response to laser interference fringes presented in the Maxwellian view. The display consisted of vertical green stationary laser interference fringes of spatial frequency 1.0 c deg(-1) which appeared in a rotatable viewing area in the form of a truncated quadrant extending from 10 to 20 degrees from fixation which was marked with a central fixation light. Results were obtained from 36 normal control subjects in order to provide a normal reference for 21 glaucoma patients and 5 OHT (ocular hypertensive) patients for whom full clinical data, including Friedmann visual fields, had been obtained. RESULTS: Abnormally high contrast thresholds were identified in 20 out of 21 glaucoma patients and in 2 out of 5 OHT patients when compared with the 95% upper prediction limit for normal values from one eye of the 36 normal age-matched control subjects. Additionally, inter-ocular differences in contrast threshold were also abnormally high in 18 out of 20 glaucoma patients who had vision in both eyes compared with the 95% upper prediction limit. Correspondence between abnormally high contrast thresholds and visual field loss in the truncated quadrants was significant in 5 patients, borderline in 4 patients and absent in 9 patients. CONCLUSION: While the glaucoma patients tested in our study invariably had abnormally high contrast thresholds in one or more of the truncated quadrants in at least one eye, reasonable correspondence with the location of the visual field loss only occurred in half the patients studied. Hence, while contrast threshold elevations are indicative of glaucomatous damage to vision, they are providing a different assessment of visual function from conventional visual field tests.

An analysis of the dependence of saccadic latency on target position and target characteristics in human subjects.

BACKGROUND: Predictions from conduction velocity data for primate retinal ganglion cell axons indicate that the conduction time to the lateral geniculate nucleus for stimulation of peripheral retina should be no longer than for stimulation of central retina. On this basis, the latency of saccadic eye movements should not increase for more peripherally located targets. However, previous studies have reported relatively very large increases, which has the implication of a very considerable increase in central processing time for the saccade-generating system. RESULTS: In order to resolve this paradox, we have undertaken an extended series of experiments in which saccadic eye movements were recorded by electro-oculography in response to targets presented in the horizontal meridian in normal young subjects. For stationary or moving targets of either normal beam intensity or reduced red intensity, with the direction of gaze either straight ahead with respect to the head or directed eccentrically, the saccadic latency was shown to remain invariant with respect to a wide range of target angular displacements. CONCLUSIONS: These results indicate that, irrespective of the angular displacement of the target, the direction of gaze or the target intensity, the saccade-generating system operates with a constant generation time.

The generation of nerve and muscle repetivie activity in the rat phrenic nerve-diaphragm preparation following inhibition of cholinesterase by ecothiopate.

1 Simultaneous extracellular recordings were made from two end-plate zones of the isolated diaphragm and from the phrenic nerve of the rat in response to stimulation of the nerve. The contractions of the diaphragm were also recorded.2 In the curarized diaphragm, the introduction of ecothiopate, a non-competitive inhibitor of cholinesterase, caused a threefold increase in the amplitude of the end-plate current and an eightfold increase in the duration at half the peak amplitude.3 In the non-curarized diaphragm, the introduction of ecothiopate caused the generation of repetitive activity (RA) in first the phrenic nerve: this was then followed by RA in the diaphragm. At that stage, nerve RA possessed a shorter latency than muscle RA. The generation time for nerve RA was 1.6 ms and for mRA, it was 2.7 milliseconds.4 Nerve RA was more labile than muscle RA; it was readily abolished by increasing the frequency of stimulation, by magnesium, by tubocurarine or by high concentrations of ecothiopate, whereas muscle RA was still generated. Steady exposure to acetylcholine abolished both forms of RA.5 Two competitive inhibitors of cholinesterase, neostigmine and ambenonium, were also shown to evoke RA in nerve and muscle. The generation times for nerve RA and muscle RA were similar to those following ecothiopate.6 It was concluded that nerve RA and muscle RA were generated after the inhibition of cholinesterase by ecothiopate as a result of the prolonged action of acetylcholine upon cholinoceptive sites on the nerve terminal and motor endplate respectively. A direct excitatory action of ecothiopate upon the phrenic nerve terminals was excluded.

Geriatric preventive health maintenance.

A preventive approach to geriatric health care should include periodic and systematic assessment of the physical, mental and social status of the elderly person. This article is a review of the important aspects of geriatric health maintenance and calls for more American data from the ambulatory-care setting, to aid in further definition of the preventive approach.

The size and shape of the optic disc in normal human eyes.

We studied the size, shape, and configuration of connective tissue of the optic disc in normal eye-bank eyes from 60 adults. The mean vertical and horizontal disc diameters were 1.88 and 1.77 mm, respectively. These figures are larger than most estimates of disc diameter using clinical image analysis methods. Within our sample, larger eyes did not have larger discs. The normal variation in disc diameter is sufficient to explain the normal variation in cup-disc ratio. The optic discs of blacks were larger and more oval than those of whites, though the axial lengths of the eyes in the two groups were not significantly different. Women's eyes and discs were smaller than those of men, possibly explaining the smaller cup-disc ratio in women. Larger optic discs and optic nerves have more optic nerve fibers than do smaller discs and nerves. Oblique insertions of the disc were detected in 18% of eyes. These were predominantly centered in the inferior disc and were more commin in white women.

Quality of vision through diffractive bifocal intraocular lenses.

Two elderly women have each received a monofocal intraocular lens in one eye and a 3M diffractive bifocal intraocular lens in the other eye. Both eyes were shown to have equivalent retinal/neural function by measuring contrast sensitivity to laser interference fringes which bypassed refractive and other defects of the ocular media. The eyes with a bifocal intraocular lens displayed a much greater depth of focus, though at the expense of diminished contrast sensitivity compared with the normal values expected for that age. Simulation experiments suggested that the observed reduction in contrast sensitivity was not adequately explained by a simple reduction in retinal illumination of the in-focus image as might intuitively be expected from the bifocal separation of incident light to two simultaneous focal points. The simultaneous superimposition of the out-of-focus image on the in-focus image must also be considered, since this caused a significant reduction in contrast sensitivity when the retinal illumination was insufficiently above the photopic luminance threshold.

Leg-length inequality in children treated by Syme's amputation.

We have reviewed the results of amputation through the ankle in the management of 37 children with congenital leg-length discrepancy, followed up for a mean of 7.6 years after operation. In general good function was achieved and 18 patients considered their activities to be unrestricted. The main factor affecting the functional result was the underlying condition for which operation had been performed. Although heel pad migration, scar rotation and os calcis remnants were seen, these could be accommodated by the prosthesis. Syme's amputation is tolerated well in the younger child and, in patients with a predicted leg-length discrepancy of over 15 cm associated with an abnormal foot, we recommend the operation as a primary procedure between the ages of 18 months and two years.

Debrisan: an effective new wound cleanser.

Debrisan (Pharmacia GB), an insoluble hydrophilic powder of polymerised dextran, has recently become available in Britain as a wound cleansing agent. So far it has proved to be an effective, if costly, agent for the initial cleaning of moist varicose ulcers, but once the slough has been removed, it has no advantage over more traditional methods in promoting ulcer healing.

Use of the Femurett adjustable prosthesis in the assessment and walking training of new above-knee amputees.

The Lic Femurett adjustable training prosthesis was evaluated on 51 above-knee amputees attending the Oxford Disablement Services Centre. In the elderly it proved superior to the Pneumatic Post-Amputation Mobility Aid (P.P.A.M.-Aid) in the assessment of their ability to use a prosthesis, and is useful for walking training once the stump is fully healed; it does not replace the P.P.A.M-Aid at the early post-operative stage.

Polyurethane gel liner usage in the Oxford Prosthetic Service.

The objective was to investigate which lower limb amputees are using Alpha polyurethane gel liners and the effects of these on comfort and suspension of their prosthesis. A retrospective study was carried out of case records of all patients issued with Alpha cushion and locking liners between 1997 and the end of January 1999. The type of liner used was compared with age, sex, level and cause of amputation, time since amputation, comfort and suspension. Modified Stanmore/Harold-Wood mobility grades; duration of use and number of liners issued per patient were recorded. Sixteen (16) patients were identified who had been prescribed Alpha cushion liners. Improved comfort was reported by all. Forty (40) patients were identified who had been prescribed Alpha locking liners. Twenty (20) of these reported improved comfort and 10 improved suspension. The average time since amputation was 18.5 years for those using cushion liners and 14.1 years for locking liner users. Fifty-two (52) of all 56 patients using Alpha cushion and locking liners had mobility grades of 4 or more. Trauma was the most common cause of amputation. This group is a relatively mobile group of amputees. All those using cushion liners reported improved comfort. Some of the locking liner users reported improved comfort and suspension but this was not universally the case.

Foot loading characteristics of amputees and normal subjects.

The foot loading characteristics of 100 consecutively attending amputees wearing their definitive prostheses were studied during their routine visits to the Artificial Limb and Appliance Centre. Results were compared with observations on 100 age and sex matched controls who were free from any locomotor disability. The parameters measured were the percentage of body weight borne on each foot, the positions of the centres of pressure under each foot and the position of the overall centre of foot pressure. The results demonstrate the range of variability of these parameters in normal subjects of different ages and provide preliminary indications of the patterns associated with different types of prostheses and different levels of amputation. The information was collected using the Double Video Forceplate (DVF) a tool developed for the rapid assessment of stance, at University College London Bioengineering Centre. It is proposed that the DVF may be useful in assisting prosthetic alignment, in clinical teaching of prosthetists, physiotherapists and doctors and in monitoring of patients with lower limb amputation.

The population of users of upper limb prostheses attending the Oxford Limb Fitting Service.

There is no central database that records the changing provision of prostheses in the United Kingdom. Experience suggests there have been some shifts in the population, particularly in the past decade. Because the detailed records of these changes are contained in the patients' medical records it is difficult to assess the substance of these data except on an individual basis; the larger picture the sifting of a centre's or many centres' data. This paper describes the analysis of one such set of records at the Oxford Limb Fitting Centre. It relates the profile of the population that attends the centre to the general population, and compares the information with that obtainable from other sources. The possible causes for the findings are discussed.

Fatigue as a presenting complaint in family practice.

The medical records of 176 patients with an isolated diagnosis of fatigue (ICHPPC-7901) were reviewed. The study population represented the experience of four family physicians in private practice and of residents and staff of a university family medicine center in Denver, Colorado, over a 12-month period. Variables included for study were age, sex, family structure, diagnostic testing, duration of symptoms, and associated final diagnosis. Women outnumbered men in the study population two to one. Fatigue occurred most frequently in people ages 15 to 34 years. Single people, both men and women, were represented in the study population at a higher rate than family members. Single women tended to have physical diagnoses associated with their fatigue, while women who were members of family units tended to have psychological diagnoses associated. Fatigue lasting longer than four months was more frequently associated with psychological problems, while symptoms less than four months in duration were more frequently associated with physical problems. Physical problems were involved in just over half the cases, with the most common being the prolonged viral syndrome. A discussion with the patient regarding his or her fatigue and its origin was documented in only about half of the cases.

Adolescent health care in family practice.

This paper describes the 12,414 health care problems of 3,657 adolescent patients visiting 12 Colorado family practices (4 rural, 3 urban, and 5 residency practices) over a one-year period. All 12 practices utilize the Family Medicine Information System, a selectively automated system for storing and analyzing medical, family, and billing data. Age-sex distribution, visiting patterns, and morbidity are described for patients between 13 and 20 years of age. The 25 most frequent adolescent diagnoses account for 74 percent of visits, and 134 diagnoses account for 95 percent of pediatric visits. Significant sex differences and differences among early, middle, and late adolescent age groups are described. All diagnostic categories are explored in detail, and comparisons are made between urban, rural, and residency practices.

Pediatric training in family practice: a core curriculum.

Official residency guidelines for pediatric training of family practice residents focus on the number of months of block time on pediatric rotations and the percentage of pediatric patients in the resident's model practice. These guidelines do not ensure competence in pediatrics. Family practice residencies need a competency-based curriculum derived from actual pediatric experience in family practice. Such a curriculum should define specific knowledge, skills, and attitudes required, define the family physician's role in handling each issue or condition, be used on a daily basis, and form a basis for evaluation of residents and curriculum. This paper describes the development and implementation of such a pediatric core curriculum at the University of Colorado Family Practice Residency.

Pediatric health care in family practice.

This paper describes the 32,926 health care problems of 9,117 pediatric patients visiting 12 Colorado family practices (4 rural, 3 urban, and 5 residency practices) over a one-year period. All 12 practices utilize the Family Medicine Information System (FMIS), a selectively automated system for storing and analyzing medical, family, and billing data. Age-sex distribution, visiting patterns, and morbidity are described for patients under 18 years of age. The 25 most frequent pediatric diagnoses account for 77 percent of visits, and 121 diagnoses account for 94 percent of pediatric visits. All diagnostic categories are explored in detail, and comparisons are made among urban, rural, and residency practices.

Evolution of the perioperative clinical nurse specialist role.

Perioperative nursing roles continue to rapidly change as we enter the twenty-first century. The need for strong leadership skills, expert clinical skills, creative management, ongoing continuing education, and research continues to grow in every department of surgical services. The clinical nurse specialist plays an important role in addressing each of these needs. Great opportunities exist within the field of nursing for perioperative nurses to expand their practice using their creativity, ideas, and skills. Using the clinical nurse specialist in the perioperative setting can foster creativity, stimulate development of new methods based on research, and maximize the delivery of high quality care by the entire OR staff.