Biomedical subjects
Publications and source records attributed to R G Smith.
This rare myasthenic disorder is the first neurologic disease found to be caused by antibodies against an ion channel complex. It presents an unusual opportunity to clarify the pathobiology of so-called receptor diseases, as well as to gain better understanding of the normal biology of acetylcholine release and its effect on neuromuscular junctions.
BACKGROUND AND METHODS: Sporadic amyotrophic lateral sclerosis is a chronic, progressive degenerative disease of the motor neurons of the spinal cord and motor cortex. The cause is unknown. Recent electrophysiologic studies in animals indicate that immunoglobulins from patients with this disease alter presynaptic voltage-dependent calcium currents and calcium-dependent release of neurotransmitters. To determine whether similar interactions might be identified biochemically, we used an enzyme-linked immunosorbent assay (ELISA) to detect the reaction of serum IgG with purified complexes of L-type voltage-gated calcium channels from rabbit skeletal muscle. The results from patients with amyotrophic lateral sclerosis were compared with those obtained from patients with other types of motor neuron disease, patients with autoimmune and non-autoimmune neurologic diseases, and normal subjects. RESULTS: Serum samples from 36 of 48 patients with sporadic amyotrophic lateral sclerosis (75 percent) contained IgG that reacted with L-type calcium-channel protein, and serum reactivity on ELISA correlated with the rate of disease progression (Spearman rank-correlation coefficient, 0.62). Reactive serum was present in only 1 of 25 normal subjects and 1 of 35 control patients with no motor neuron disease. Antibodies to L-type voltage-gated calcium channels were identified in 6 of 9 patients with Lambert-Eaton syndrome, and in 3 of 15 patients with Guillain-Barré syndrome. CONCLUSIONS: Antibodies to L-type voltage-gated calcium channels are present in the serum of patients with amyotrophic lateral sclerosis, and antibody titers correlate with the rate of disease progression. Together with previous data, these results suggest a role for autoimmune mechanisms in the pathogenesis of sporadic amyotrophic lateral sclerosis.
This paper reviews three recent decisions of the Judicial Committee of the Privy Council on appeal from decisions of the Professional Conduct Committee of the General Dental Council, in which questions of general anaesthesia, sedation and resuscitation were raised. The recommendations of the Poswillo Report on general anaesthesia, sedation and resuscitation in dentistry of March 1990 are considered with respect to these three cases, and an assessment made as to whether or not the incidents which gave rise to them would have occurred had the recommendations been implemented. The implications of the Poswillo Report for the maintenance of professional standards of conduct by the General Dental Council in relation to the use of general anaesthesia, sedation and resuscitation are discussed.
During development, the genotype of the zygote determines the nature of the gonad, which then determines the male or female phenotype. The molecular events underlying this process are just beginning to be defined. A single treatment of chicken embryos with an aromatase inhibitor (which blocks the synthesis of estrogen from testosterone) at a stage when their gonads were bipotential caused genetic females to develop a permanent male phenotype. These sex-reversed females developed bilateral testes that were capable of complete spermatogenesis and had the physical appearance and behavior of normal males. This result identifies aromatase as a key developmental switch in the sex determination of chickens.
The on-alpha ganglion cell in the area centralis of the cat retina receives approximately 450 synapses from type b1 cone bipolar cells. This bipolar type forms a closely spaced array (9 microns), which contributes from 1 to 7 synapses per b1 cell throughout the on-alpha dendritic field. Here we use a compartmental model of an on-alpha cell, based on a reconstruction from electron micrographs of serial sections, to compute the contribution of the b1 array to the on-alpha receptive field. The computation shows that, for a physiologic range of specific membrane resistance (9500-68,000 omega.cm2) and a linear synapse, inputs are equally effective at all points on the on-alpha dendritic tree. This implies that the electrotonic properties of the dendritic tree contribute very little to the domed shapes of the receptive field center and surround. Rather, these shapes arise from the domed distribution of synapses across the on-alpha dendritic field. Various sources of "jitter" in the anatomical circuit, such as variation in bipolar cell spacing and fluctuations in the number of synapses per bipolar cell, are smoothed by the overall circuit design. However, the computed center retains some minor asymmetries and lumps, due to anatomical jitter, as found in actual alpha-cell receptive fields.
Left ventricular venting has many physiologic and practical benefits. A venting technique is described that employs a simple, closed system which allows the perfusionist to monitor left ventricular distention. By monitoring the left ventricular volume the perfusionist can regulate the degree of negative pressure on the vent and thus reduce the chance of air entering the heart.
A computational language was developed to simulate neural circuits. A model of a neural circuit with up to 50,000 compartments is constructed from predefined parts of neurons, called "neural elements". A 2-dimensional (2-D) light stimulus and a photoreceptor model allow simulating a visual physiology experiment. Circuit function is computed by integrating difference equations according to standard methods. Large-scale structure in the neural circuit, such as whole neurons, their synaptic connections, and arrays of neurons, are constructed with procedural rules. The language was evaluated with a simulation of the receptive field of a single cone in cat retina, which required a model of cone-horizontal cell network on the order of 1000 neurons. The model was calibrated by adjusting biophysical parameters to match known physiological data. Eliminating specific synaptic connections from the circuit suggested the influence of individual neuron types on the receptive field of a single cone. An advantage of using neural elements in such a model is to simplify the description of a neuron's structure. An advantage of using procedural rules to define connections between neurons is to simplify the network definition.
A modified functional analysis was used to assess the behavioral function of a profoundly retarded man's self-injurious behavior (SIB). Results of that analysis showed that the behavior was most likely to occur in a demand context (self-care instructions) but was maintained by positive reinforcement in the form of attention and physical contact. The results of the functional analysis also prescribed a treatment involving differential reinforcement of alternative behavior (DRA). Further investigation showed that other aberrant behaviors, such as aggression and disruption, were members of the same functional response class as SIB. The differential reinforcement of alternative behavior (DRA) procedure effectively reduced those behaviors while compliance to a self-care acquisition task increased markedly. The results are discussed in terms of the importance of determining behavioral function prior to treatment.
AIMS: To evaluate the accuracy of clinical diagnosis by specialists in geriatric medicine and to compare this with a previous study involving non-specialists. METHOD: Clinical and necropsy diagnoses from consecutive hospital inpatient deaths from the University Department of Geriatric Medicine were analysed for discrepancies at regular audit meetings. Three main categories of diagnosis were considered and any therapeutic implications discussed. RESULTS: Between 1987 and 1989 necropsies were performed on 100 patients (38 men, 62 women, aged 63 to 99 years) from a total of 207 deaths, a necropsy rate of 50%. There was complete agreement between necropsy and clinical diagnoses in 32% of cases. Disagreement involved the main diagnosis in 28%, contributory conditions in 32%, and cause of death in 34%. In 10% of cases the diagnostic discrepancy was considered therapeutically important. Specialist geriatricians correctly diagnosed the main diagnosis in 72% of cases; non-specialists in the previous study were correct in only 47% of cases. CONCLUSION: Specialist geriatricians diagnose elderly people more accurately than non-specialists. But rates of misdiagnosis are still significant and necropsies continue to be a useful form of audit.
A repeated measurement design was employed in the study of acute symptoms of eye and respiratory tract irritation resulting from occupational exposure to sodium borate dusts. The symptom assessment of the 79 exposed and 27 unexposed subjects comprised interviews before the shift began and then at regular hourly intervals for the next six hours of the shift, four days in a row. Exposures were monitored concurrently with a personal real time aerosol monitor. Two different exposure profiles, a daily average and short term (15 minute) average, were used in the analysis. Exposure-response relations were evaluated by linking incidence rates for each symptom with categories of exposure. Acute incidence rates for nasal, eye, and throat irritation, and coughing and breathlessness were found to be associated with increased exposure levels of both exposure indices. Steeper exposure-response slopes were seen when short term exposure concentrations were used. Results from multivariate logistic regression analysis suggest that current smokers tended to be less sensitive to the exposure to airborne sodium borate dust. There was no indication that anhydrous sodium borate was more potent than the other sodium borates in this work environment.
Many individuals who exhibit self-injurious behavior (SIB) also exhibit self-restraint. Three hypotheses about the determinants of self-restraint have been suggested: (a) Self-restraint is maintained by escape from or avoidance of aversive aspects of SIB, (b) self-restraint and SIB are members of the same functional class, and (c) self-restraint and SIB are functionally independent. This study examined a method by which the relationship between self-restraint and SIB may be investigated using functional analysis. Data were collected on the self-restraint and SIB exhibited by 5 mentally retarded males, while conditions suspected to maintain SIB were manipulated. Results suggested that self-restraint, like SIB, may be maintained by idiosyncratic contingencies. Implications of an understanding of self-restraint for the analysis and treatment of SIB are discussed, as are some general possibilities for future research.
A dopaminergic neuroblastoma was derived using somatic cell fusion of rat embryonic mesencephalon cells and the murine neuroblastoma-glioma cell line N18TG2. The resulting interspecies hybrid, named MES23.5, has retained a stable phenotype and karyotype for a continuous culture period of 1 year. The hybrid exhibits several properties that suggest that the parent primary neurons originated in the substantia nigra. The cell line contains tyrosine hydroxylase, which is identifiable both by biochemical and immunological methods and synthesizes dopamine, but no other catecholamine. Additionally, the cell line expresses apparent voltage-gated CA2+ channels as measured by high-affinity omega-conotoxin binding. The MES23.5 omega-conotoxin receptors are of similar affinity class to those found in adult rat mesencephalon. No dihydropyridine receptors, as measured by PN200-100 ligand binding, are present. None of these properties are found in the N18TG2 parent. At least three neuronal features, namely, tyrosine hydroxylase, dopamine synthesis, and omega-conotoxin receptor expression, are quantitatively elevated after sustained treatment with cAMP analogs. The cell line expresses a complex range of neural properties found in the dopaminergic neurons of the substantia nigra, and may therefore be useful elucidating further details of their cell biology.
Complications of fronto-basal trauma can, as a function of their severity, be divided into three classes: life-threatening situations, functional complications and cosmetic defects or facial deformities. They find their origin in the type of trauma, the extent of the lesions of bone and soft tissues, as well as in their timely management and quality of treatment. The etiology of the most common complications and their significance are covered with accent on inadequate primary treatment, insufficient repair of dural lesions, inadequate drainage, unstable osteosynthesis, insufficient treatment of scalp- and frontal defects, and finally the lack of antibiotic prophylaxis. The major complications of frontobasal trauma such as chronic cerebral spinal fluid fistulae and pneumocephalus are reviewed. Attention is also given to the importance of adequate drainage in cases of chronic ethmoidofrontal sinusitis, and on the treatment of osteomyelitis and sinus cysts. The therapeutic possibilities in patients with tissue deficits, i.e. reconstruction of frontal skull defects using autologous hip and rib material, as well as split calvarial bone grafts is discussed.
The article illustrates the importance of face lifting and S.M.A.S. tightening as an adjunct to the aesthetic aspect of maxillo facial surgery, for instance in combination with extreme mandibular set back or advancement in adults. The theory and basic techniques of the face lifting procedure and the S.M.A.S. tightening technique are described. A clinical example is presented. The indications pre- and postoperative management and complications have been mentioned.
Liposuction is a relatively recent surgical technique used in body contouring plastic surgery to correct fatty dysharmonies. It is of particular interest to the maxillo-facial surgeon to treat submental fat excess. This relatively easy technique is described, using a few clinical examples. Indications in maxillo-facial surgery are the correction of "double chin" deformity and increased submental fullness after orthognathic surgical procedures as mandibular setback, as well as an adjunct to rhytidectomy.
Two hundred and four patients discharged from an acute geriatric unit were given an interim discharge summary for delivery to their General Practitioner (GP). All but three summaries were received by the practices. Information regarding mode and timing of receipt was available in 191 patients. The summaries were received in a median of 1.0 day in both those living alone and those living with family; 75% of summaries had been received within two days of discharge and 93% within four days. General practitioners collected the summaries from patients' homes in a high proportion of both groups. Interim discharge summaries should be given to elderly patients for delivery to their GPs: this is both reliable and rapid, and clearly more cost-effective than any other form of delivery.
A 48-year-old man was supported for 164 days with Symbion biventricular assist devices. During that time, his cytotoxic antibody screen fell from 97% positivity to less than 10%, enabling cardiac transplantation. Complications during the implantation included a 3-minute episode of amaurosis fugax, one positive blood culture, and anemia, which responded to decreased frequency of blood drawing. He is now alive 7 months after transplantation.
The cDNA encoding the murine Mx1 protein, a mediator of resistance to influenza virus, was inserted into a replication-competent avian retroviral vector in either the sense (referred to as Mx+) or the antisense (referred to as Mx-) orientation relative to the viral structural genes. Both vectors produced virus retaining the Mx insert (Mx recombinant viruses referred to as Mx+ and Mx-) following transfection into chicken embryo fibroblasts (CEF). Mx protein of the appropriate size and nuclear localization was expressed only in CEF cells infected with the Mx+ virus. Mx expression was observed in all Mx(+)-infected cells and was stable during long-term culture. Cells infected with the Mx+ virus were resistant to infection by human influenza A/WSN/33 (H1N1) and avian influenza viruses A/Turkey/Wisconsin/68 (H5N9) and A/Turkey/Massachusetts/65 (H6N2), but were susceptible to infection by the enveloped RNA viruses Sindbis and vesicular stomatitis virus (VSV). Normal CEF and cells infected with the Mx virus were susceptible to influenza A, Sindbis, and VSV. The synthesis of influenza proteins, especially the larger polymerase and hemagglutinin proteins, was reduced in Mx+ retrovirus-infected cells superinfected by influenza A.