Evidence for virtual Compton scattering from the proton.
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Biomedical subjects
Publications and source records attributed to S Kuhn.
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We investigated the feasibility of using the primate E complement receptor (CR1), in concert with Ag-based heteropolymers (AHP), as a potential therapy to remove autoantibodies from the circulation. AHP are prepared by cross-linking an anti-CR1 mAb with the acetylcholine receptor (AChR), the principal target Ag in myasthenia gravis. In vitro studies demonstrate that this methodology facilitates specific, rapid, and quantitative binding of an anti-AChR mAb to primate Es. In vivo experiments in rhesus monkeys indicate that AHP-mediated binding of an anti-AChR mAb to Es leads to the clearance of the mAb from the circulation. Once bound to the E via the AHP, the autoantibody is transported to the liver and spleen, where it is degraded without destruction of the E. It is therefore likely that the complexes of AHP and target mAb, when bound to Es, are recognized in vivo and processed by a mechanism quite similar to that which occurs when complement-opsonized immune complexes, bound to primate Es, are cleared from the circulation. It may be possible to extend and generalize this work to allow for the development of a simple, noninvasive therapy that can be made specific for the treatment of several different autoimmune diseases.
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OBJECTIVE: To determine if complexes containing monoclonal antibodies to CR1 cross-linked with antigen (antigen-based heteropolymers [AHP]) can bind the corresponding autoantibody to primate erythrocyte CR1 and promote autoantibody clearance from the circulation. METHODS: AHP were constructed by cross-linking double-stranded DNA (dsDNA) to monoclonal antibodies to CR1. The ability of AHP to facilitate binding of human anti-dsDNA antibodies to primate erythrocytes was studied in vitro using a variety of radioimmunoassays (including Farr assays), enzyme immunoassays, and fluorescence-activated cell sorting. In addition, we used a monkey model to study in vivo the AHP-mediated clearance of passively infused human anti-dsDNA antibodies. RESULTS: Large amounts of lupus IgG anti-dsDNA antibodies can be specifically bound to human erythrocytes via the complexes, and studies in 2 rhesus monkeys indicate that the erythrocyte-bound antibodies are rapidly cleared from the circulation. CONCLUSION: This methodology may allow for development of a new therapy to facilitate autoantibody clearance in autoimmune disease.
The purpose of the present study was to develop and test attitude scales for menopause and estrogen replacement therapy (ERT) using 116 college-aged and 136 mid-aged women. Factor scores indicate that mid-aged women view menopause in a more benign fashion than college-aged women and are more likely to view ERT as positive while recognizing side effects. Restricted variability on ERT attitude items suggests limited knowledge or opinions and a need for education across ages. Women's perceptions of ERT are in terms of a solution for immediate relief of symptoms in contrast to current medical recommendations that emphasize ERT as long-term disease prevention therapy.
There is increasing evidence that "anticraving" drugs are promising agents in the treatment of alcoholics. Clinical studies indicate favorable effects of drugs with different pharmacological profiles (e.g., dopaminergic, serotonergic, anti-opioidergic, antiglutamatergic) on abnormal drinking behavior and relapse tendencies. Interactions with the limbic reward system seem to be involved. As several drugs will probably be registered in Germany, the need for integrating these drugs in a complex rehabilitation program is emphasized. Many clinical issues regarding the practical use of these drugs await further clarification.
Autoantibodies in systemic lupus erythematosus which cross-react with double stranded DNA and intermediate filament proteins are frequently reported. However, little is known about the origin and the target of these antibodies. In this paper, a polyspecific monoclonal antibody, XY12, produced by the immunization of genetically non-autoimmune mice with a DNA-protein complex is detailed. Its antigen binding patterns are very similar to the autoantibodies. The data suggest that these autoantibodies may be triggered by a circulating nucleoprotein.
Growth hormone (GH) secretion, stimulated by the dopamine D1 and D2 receptor agonist apomorphine, was assessed in 55 alcohol-dependent patients before detoxification (on the day of admittance to hospital) and after 7 days of treatment on the ward (day 8). Patients who relapsed early (i.e., within 3 months after detoxification) showed significantly blunted GH secretion before detoxification, compared with both healthy controls and patients who abstained for 6 months. Among early relapsing patients, GH secretion was blunted whether or not patients were acutely intoxicated on the day of admittance to hospital. However, for patients who abstained during observation, a blunting effect of acute ethanol consumption on GH secretion was demonstrated. On day 8, a trend toward blunted GH secretion was found in early relapsing patients only when GH response over infusion time was assessed. Therefore, GH blunting, and no other variable indicating the clinical course of the disease, was associated with early relapse in alcohol-dependent patients. These findings are evidence of reduced dopamine receptor function in a subgroup of early relapsing alcohol-dependent patients during chronic intoxication.
We describe eleven mid-western Canadian aboriginal infants with a unique, progressive muscle disorder. All except one had muscle biopsy and/or autopsy. The infants were normal newborns who rapidly developed rigidity of all skeletal muscles, with early, respiratory insufficiency. Death occurred before 18 months of age. Electromyography showed increased insertion activity and profuse fibrillation potentials; motor unit potentials and interference pattern are normal until late in the course. Pathologic features include progressive, granular to powdery Z-band transformation, myofibrillar loss, and muscle regeneration. SDS-gel electrophoresis of one muscle sample revealed increased 54kDa and reduced 80kDa protein fractions. This disease differs from other conditions with Z-band alterations because of continuous muscle activity and relentless clinical progression. The clinical features, elevated serum creatine kinase, electromyographic and muscle biopsy findings suggest a dystrophic process. The recognition of this condition as an autosomal recessive disorder allows appropriate genetic counselling.
Lisuride--a compound with mainly dopamine d2-agonistic, but also dl-antagonistic and serotonergic properties was choosen in 1.0 mg daily dose as an anticraving drug for keeping alcoholics abstinent who had been included in a randomized double-blind placebo-controlled trial for 6 months. Preliminary results indicate that in the first 55 recruited patients the overall abstinence-rate dropped from 85% after 3 months to 47% after 6 months. Predictors of relapse were early onset of alcohol-related problems, a high number of preceding detoxification and rehabilitation treatments, intermittant drinking habits, less feeling of guilt and low harm avoidance in the TPQ by Cloninger. More details will be given after completing the study when the code is lifted.
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STUDY OBJECTIVE: To compare and contrast the modes of death in a neonatal (NICU) and a pediatric (PICU) intensive care unit. DESIGN: Retrospective analysis of patient records. SUBJECTS: All newborn infants and children (< 17 years of age) who died in the NICU and PICU at the University of Alberta Hospitals, Edmonton, between Jan. 1, 1990, to Dec. 31, 1991. RESULTS: The mortality rate in the PICU was 8.7% (73/839) compared with 5.6% (75/1333) in the NICU (p = 0.007). Withdrawal of therapy was the most common cause of death in both units and occurred more commonly in the NICU (NICU = 69% vs PICU = 34%; p = 0.01). There were significantly more deaths as a result of failed cardiopulmonary resuscitation (CPR) in the PICU than in the NICU (29% vs 13%; p = 0.046). Death after no-CPR orders occurred with equal frequency in both units (NICU 17%; PICU 15%). Brain death accounted for 22% (16/87) of PICU deaths; no infant in the NICU was declared brain dead (p < 0.05). When deaths resulting from brain death and failed CPR were excluded, there was no significant difference between the two units regarding withdrawal of therapy (NICU 80% vs PICU 69%) and no-CPR orders (NICU 20% vs PICU 30%). CONCLUSIONS: This study confirms that both withdrawal of therapy and no-CPR orders are part of current clinical practice in both the NICU and PICU settings. The ethical foundations and implications of these practices need further elaboration.
A group of 26 Crohn's disease patients was compared to a healthy control group with regard to their zinc status in plasma, urine, hair, and lymphocytes. A method for lymphocyte preparation, which was in part newly designed, was used; it proved to be very effective as to recovery and purity of the harvested cell fraction. Results of the study suggest that an accurate estimation of zinc status can be more reliably obtained by determination of lymphocyte zinc--provided the cell preparation described is used--than by using any other of the examined body compartments.
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Total splenectomy, especially in children, results in diminished ability to combat infection by capsulated bacteria. It is, however, uncertain how much splenic tissue is needed to maintain this ability. In this experimental study on baboons, in situ remnants after partial splenectomy were examined to evaluate regeneration and phagocytic function after injection of dual-labelled liposomes into their splenic arterial supply. The results showed that resection of as much as two-thirds of the spleen in baboons allowed sufficient regeneration to support adequate macrophage phagocytic function.
In treatment of in-patients with chronic neurotic disorders we tried both to reduce distress in the therapeutic team (doctors, nurses, other therapists) as usually caused by those patients, and to improve outcome of treatment. Therefore, three to five guidelines on how to deal with the patient were given to the therapeutic team, and illustrated by possible literal statements to the patient. The guidelines aimed at a general interactional approach to the patient and did not determine specific therapeutic interventions. They were set up following principles of Brief Therapy as developed at the Mental Research Institute in Palo Alto. Results of our intervention in treatment of ten patients are reported. The therapeutic team rated the guidelines generally as positive. The therapeutic outcome varied greatly. A comparison with a matched pair control group showed a favourable tendency. Initial ratings by the team of the prescriptions predicted eventual improvement of the patients.
OBJECTIVE: To assess patients' satisfaction with postoperative pain relief. DESIGN: A descriptive and questionnaire study of patients' experience. SETTING: Two surgical and two gynaecological wards. PATIENTS: 50 Patients admitted to hospital for cholecystectomy and 51 admitted for hysterectomy. MAIN OUTCOME MEASURES: Visual analogue scales with no divisions were completed by the patients immediately after each dose of postoperative analgesia was administered throughout their stay in hospital. A questionnaire completed on the fifth postoperative day recorded patients' recollections of their experience. Opinions were also sought from medical and nursing staff. RESULTS: During the first 24 hours after surgery recorded pain levels were 60% of the maximum and were not influenced by age, sex, or the type of operation performed. The median interval between the return of pain and a further injection of analgesic was 2 hours (interquartile range 1 to 3.5 hours). Expectations of pain relief were low, and for 70% of the patients the pain was at least as bad as they had expected. Only half of the medical and nursing staff questioned thought that postoperative analgesia should relieve pain completely; drugs were prescribed and administered with too little attention to the patient's response and too much concern about adverse effects and opioid dependence. CONCLUSIONS: The results suggest that the standard of postoperative pain relief is poor because of inadequate education of patients in what to expect (and demand), and of medical and nursing staff in how to prescribe and administer analgesia with reference to individual drug response.
We report a high resolution liquid chromatography method for simultaneous determination of lidocaine, mepivacaine and bupivacaine in serum using cyclicine as a standard. Drugs are extracted from serum using dichloromethane in an alkaline medium type columns in a mobile phase with 0.1 M phosphate buffer at pH 7.5, methanol and acetonitrile (33:17:50) were used for separation. Spectrophotometric measurement was performed at 207 nm. In a concentration ranging from 0.5 to 8 micrograms/ml, r values of 0.997, 0.989 and 0.998 were obtained for lidocaine, mepivacaine and bupivacaine, respectively. The coefficient of variation estimated at 2 micrograms/ml was 2, 19, 2.76 and 2.48%, respectively. A maximal error of 4.5%, 3.6% and 2.9% found for "inter day" repeated measurement at the above concentration for each drug. Thus, high sensitivity, reproducibility and relative simpleness of the method are demonstrated for its clinical use in determination of serum levels of local anesthetics.