Biomedical subjects
Publications and source records attributed to M E Smith.
Focused, high-intensity therapeutic ultrasound was used to treat 69 selected patients with uncontrollably elevated intraocular pressure (IOP). This new technique selectively thins scleral collagen, and produces focal damage to the ciliary epithelium. These tissue modifications provide a reduction in IOP pressure to 25 mmHg or less in 83% of patients with a minimum three-month follow-up period.
Studies were carried out in Edinburgh to determine the nature, causes and economic consequences of hand injuries requiring more than one visit to hospital. Information on 236 out-patients was collected during a period of six weeks and on 122 in-patients during a period of six months. In both studies, follow-up was by postal questionnaire six weeks after injury. More serious injuries requiring admission to hospital occurred at home (39%) than at work (27%), and of injuries treated on an out-patient basis, the highest proportion (30%) happened at sport. As a result, demands on hospital services were highest in the later part of the day and evening. The main causes of injury were falls at home, at work, in the street or through violence, and only a few were caused by industrial machinery. Two-thirds of the patients were employed, and the mean time off work was three weeks for out-patients and seven weeks for in-patients. Although Edinburgh may not be typical of other cities in the United Kingdom, the studies suggest that even so-called 'trivial' hand injuries make considerable demands on hospital services, with related costs to the individual, the employer and the nation.
A system is described which allows an accident department doctor, who has no specific knowledge of computer operation, to record standardised demographic and clinical details of patients with hand injuries. An educational element is present which suggests possible diagnoses following specific injuries and most of the recording is carried out using a light pen, thus obviating the need for any keyboard skills. The information obtained is stored on 'floppy' discs (each disc can hold details of up to five hundred patients) allowing straightforward storage, retrieval and analysis of information by either micro or main frame computer.
The enzyme UDP-N-acetylglucosamine: dolichyl phosphate, N-acetylglucosamine-1-phosphate transferase initiates the synthesis of the oligosaccharide chain of complex-type glycoproteins. In view of the high content of glycoprotein in peripheral nerve myelin, the properties of this enzyme, its changes with age, and the effect of the specific inhibitor tunicamycin were investigated. The enzyme activity in rat peripheral nerve homogenate was completely dependent on the presence of exogenous dolichyl phosphate as well as Mg2+ and a detergent (Triton X-100) and was also greatly stimulated by a high salt concentration (0.4 M KCl) and AMP. The highest specific activity was present in the postmitochondrial membranes. The specific activity in postmitochondrial membranes in the presence of exogenous dolichyl phosphate reached a maximum at 17 days and remained relatively high throughout development, up to 2 years of age, but the activity was much lower when dolichyl phosphate was not added. This indicates that the enzyme level does not decrease with age, but that the content of the lipid cofactor may limit glycoprotein synthesis in vivo. Tunicamycin (5 micrograms) was injected intraneurally into 24-day-old rat sciatic nerve, and the enzyme was assayed from 1 to 24 days after injection. The specific activity of the transferase remained at low levels (5-40% of the level in control nerve) in most injected nerves assayed throughout this postinjection period. A protein previously identified as the unglycosylated P0 protein was synthesized in vitro by the tunicamycin-injected nerve and could be demonstrated to be incorporated into myelin in large amounts at 2 days and in small amounts at 6 days after injection.(ABSTRACT TRUNCATED AT 250 WORDS)
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The management of hand injuries forms an important part of the hospital accident and emergency service, and early recognition and informed management are essential for a favourable outcome (Frazier et al., 1978). In Edinburgh a routine system of hand management is well established and includes the training of casualty officers. In order to evaluate the effectiveness of the hand service in the Accident and Emergency Department, Royal Infirmary of Edinburgh, a prospective study was undertaken to compare the outcome of treatment of hand injury by a routine system with treatment over a similar period by more experienced registrars in hand surgery training posts (Hand Fellows).
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Phosphatidylinositol phosphodiesterase activity was determined in cytosol prepared from rat slow (soleus) and fast (extensor digitorum longus) muscles. The substrate was prepared by incubation of sarcoplasmic reticulum with myo-[2-3H]inositol. The enzyme hydrolysed both membrane-bound and extracted phosphatidylinositol. The activity determined with the isolated phospholipid exhibited an optimum at pH 5.5. Ca2+ ions stimulated the activity. The enzyme specific activity was higher in cytosol prepared from soleus muscle than in that from extensor digitorum longus muscle. After section of the motor nerve, the activity of the enzyme increased in both muscles up to 36 h and then declined. A function for this enzyme in the control of acetylcholine sensitivity in muscle is discussed.
A new system for the detection and treatment of hypothermia in newborn lambs was evaluated on 30 commercial farms. This system comprised the detection of hypothermia with the aid of an electronic thermometer, the reversal of hypoglycaemia in lambs aged more than five hours by an intraperitoneal injection of glucose solution, warming in air at 40 degrees C and careful management after warming. Of all lambs treated, 69 per cent were alive one week later. The majority of lambs which were treated and lived were subsequently reared on ewes. Treatment was more successful in lambs aged less than five hours (76 per cent) than in older lambs (64 per cent). Higher success rates were recorded when the hypothermia was detected in the temperature range of 37.0 to 39.0 degrees C (83 per cent) than when it was only detected at a temperature of less than 37.0 degrees C (65 per cent). Twins and triplet lambs were more susceptible to hypothermia than singles.
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The introductory review amplifies the finding that simply holding lymphocytes in vitro reversibly compromises their ability to enter lymph nodes from the blood, although entry into the spleen is unaffected. The differential migration of T and B lymphocytes from the blood, lymphocyte traffic in athymic rats, and the secretion of a sulphated glycoconjugate by high endothelial cells in lymph nodes are also discussed. Original data are presented concerning the effects of varying the conditions under which lymphocytes are held in vitro (time, temperature, medium, centrifugation) on their ability to enter lymph nodes and also on their surface morphology. In general, conditions that reduced the number of microvilli and induced surface blebbing also tended to affect the delicate function of crossing specialized vascular endothelium; but there was no simple relationship between morphology and migratory behavior. The localization of lymphocytes to the bone marrow was augmented by holding them in vitro, and this effect was greater after holding at room temperature (RT) than at 0 degree C, in contrast to impaired entry into lymph nodes. Small amounts of heparin (10 units) injected along with lymphocytes significantly reduced early localization in lymph nodes. These findings have practical implications for the design of lymphocyte traffic experiments and are relevant to the mechanism of lymphocyte attachment to vascular endothelium, since the well-known effect of trypsinizing lymphocytes can be reproduced by maintenance in vitro.
General aspects of metabolic features of the most prominent CNS intermediate filament proteins, the 200,000 (200K), 150,000 (150K), and 70,000 (70K) dalton proteins of the neuron, and the glial fibrillary acidic protein (GFAP) have been explored using the incubated spinal cord slice from the rat. Measurement of short-term uptake of 3H-labeled amino acids into the individual proteins separated on polyacrylamide gels revealed that of the three neurofilament proteins, 200K was most metabolically active, 150K was less active, and 70K contained very little incorporated radioactivity. Glial fibrillary acidic protein based on Coomassie blue stain affinity showed less metabolic activity than any of the neurofilament proteins. Those relationships were constant at all ages, but the metabolic activity of all CNS intermediate filaments decreased with age. When Ca2+ was present in the medium of the incubated slices, the intermediate filaments were rapidly destroyed, but GFAP was more resistant to degradation than the neurofilament proteins. GFAP and probably the neurofilament proteins also were relatively resistant to Ca2+-activated degradative mechanisms in spinal cords of rats at younger ages (15 day) than in those of older animals (10-18 months). It is likely that the Ca2+ activated protease is less active in developing animals in which the nerve tracts are still elongating, than in adults. These results suggest that GFAP is less active metabolically and more resistant to degradation than the neurofilament proteins at all stages of maturation, but that metabolic activity of all CNS intermediate filaments decreases with age while the susceptibility to degradation increases.
Adipose tissue is the major site of estrogen formation in postmenopausal women. We have previously reported (Simpson, E.R., Ackerman, G.E., Smith, M.E. and Mendelson, C.R. (1981) Proc. Natl. Acad. Sci. (U.S.A.) 78, 5690-5694; Mendelson, C.R., Cleland, W.H., Smith, M.E. and Simpson, E.R. (1982) Endocrinology 111, 1077-1085) that aromatase activity of human adipose stromal cells in culture is stimulated by glucocorticoids and by dibutyryl cyclic AMP (Bt2-cAMP). In order to establish which physiological factors might stimulate aromatase activity of these cells by activation of adenylate cyclase, we have investigated the roles of adrenocorticotropin (ACTH) and isoproterenol to increase cyclic AMP levels and stimulate the aromatization of androstenedione. In the presence of methylisobutylxanthine (MIX), ACTH stimulated cyclic AMP formation and aromatase activity in a time- and concentration-dependent manner. The concentration of ACTH required for half-maximal stimulation was approximately 10(-8) M. Isoproterenol, in the presence of MIX, stimulated cyclic AMP formation in a time- and concentration-dependent fashion, and also stimulated aromatase activity. These effects of isoproterenol appeared to be mediated by binding of the agonist to a population of beta-adrenergic receptors. On the basis of these and our previous studies, we suggest that ACTH may play an important role in stimulating estrogen formation by human adipose tissue, both directly, and by stimulating the adrenal cortex to produce both substrate, androstenedione, and inducing agent, namely cortisol.
The morning glory anomaly is a rare congenital clinical entity that results from abnormal optic nerve development. In our series of 30 patients, followed for a mean duration of 10.3 years, 11 developed associated retinal detachments. These detachments followed a variable clinical course, including spontaneous reattachment and even redetachment, and may result from an abnormal communication between the subarachnoid space of the optic nerve and the subretinal space, allowing cerebrospinal fluid to accumulate subretinally. The clinical findings (including ultrasonography, computed tomography, and electrophysiologic testing), natural history, complications, and therapeutic indications are discussed.
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DNA levels were measured in the spinal cords of Lewis rats during the development of and recovery from experimental allergic encephalomyelitis (EAE). Spinal cord DNA was first increased 11 days after immunizing the rats with guinea pig myelin and rose to levels four times that of the Freund's adjuvant controls at day 14, then subsided after day 22. Spinal cord DNA was still 150% of control levels 60 days after immunization. These DNA changes were compared with fluctuations in spinal cord acid proteinase in the same animals. Acid proteinase activity in EAE spinal cord increased later than the rise in DNA and attained a level of 170% of control at days 15-17, then subsided. Spinal cord DNA was higher in rats immunized with whole myelin than in those administered equivalent amounts of purified myelin basic protein. Furthermore DNA was higher in spinal cords of rats immunized with a larger dose of myelin (1.0 mg) than with a lower amount (0.5 mg). Various protease inhibitors including pepstatin, nitrophenyl p-guanidino benzoate, polylysine, and dipropionyl rhein, previously shown to protect Lewis rats against EAE, suppressed the increase of DNA in the spinal cord. Measurement of DNA increases in the spinal cord of EAE animals provides a convenient reproducible measurement of the severity of inflammation in the CNS and provides an objective criterion for assessment of the efficacy of various agents screened as possible therapeutic treatment for multiple sclerosis.
Acetylcholinesterase (AChE) was extracted in a high-saline medium from gastrocnemius muscles of rat embryos and young rats aged 14 days' gestation to 40 days post partum. The molecular forms of the enzyme were separated by low-salt precipitation, followed by velocity sedimentation. During gestation, all molecular forms increased in activity, particularly the 16 S (A12) form. During the first 2 weeks of life, there was a large increase in the activity of soluble AChE (G forms), whilst the activity of insoluble AChE (A forms) was reduced. Denervation of the muscle reversed the change in the relative proportions of the molecular forms. The embryonic pattern of activities of AChE forms persisted in cultures of myotubes obtained at 20 days' gestation and maintained in the absence of spinal cord. When myotubes were maintained in medium previously conditioned by developing spinal cord explants, 16 S AChE declined while the soluble (4 and 6 S) forms increased in activity in a manner resembling that seen in early postnatal muscles in vivo. beta-Endorphin (beta-EP) immunoreactivity was detected in the spinal cord-conditioned medium and was identified by HPLC and ion-exchange chromatography as beta-EP-(1-31) plus its shortened and N-acetylated forms. Cultivation of myotubes in the presence of synthetic camel beta-EP resulted in a reversible change in the pattern of AChE forms which was similar to that seen with spinal cord-conditioned medium. These studies provide evidence for the neuroregulation of AChE A and G forms in immature skeletal muscle. A major candidate for this role is beta-EP, produced and released by developing spinal cord.