Biomedical subjects
Publications and source records attributed to J Dougherty.
A 20-year-old woman presented with an apparent acute dystonic reaction after only five doses of cimetidine (Tagamet). The patient was on no other medications with the exception of oral contraceptives. Emergency administration of IV diphenhydramine HCL brought rapid reversal of this acute dystonic reaction without any neurological sequelae. To our knowledge, this is the first reported case of an acute dystonic reaction associated with cimetidine.
One hundred twenty knees were examined prospectively with both axial computed tomography (CT) and magnetic resonance (MR) imaging to compare the value of these techniques in patients with clinical evidence of meniscal tears. Sixty-four of these knees were subsequently evaluated with diagnostic arthroscopy. In this group, CT was superior to MR imaging for meniscus evaluation in 29.7% of the knees, equal to MR in 54.7%, and inferior to MR in 15.6%. Although surface-coil MR imaging shows great promise and has numerous advantages over more conventional techniques, this preliminary experience suggests that, at least with certain imaging equipment and techniques, CT may be slightly more efficacious than 0.5-T MR imaging in meniscus evaluation. However, further comparative studies at higher field strengths are needed before the relative roles of CT and MR imaging can be established.
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Hyperthyroidism was diagnosed in 4 cats with congestive heart failure. Dyspnea and anorexia were observed in 3 of the 4 cats. In each cat, a holosystolic left and/or right apical heart murmur was auscultated. In 3 cats, a prominent extra heart sound (gallop rhythm) was auscultated. All cats had a palpably large thyroid lobe(s) and weight loss. The laboratory and ECG changes were similar to those reported for feline hyperthyroidism. Moderate-to-severe pleural effusion and cardiomegaly were detected via radiography in all cats. Some cats had radiographic signs of pulmonary venous engorgement and pulmonary edema. Echocardiography revealed cardiac dilatation and low left ventricular shortening fraction (wall motion) in all cats. Three cats responded initially to cardiac drugs and propylthiouracil or thyroidectomy. One of these died later, presumably from an adverse reaction to propylthiouracil, and the others died from recurrent congestive heart failure (1) or postoperative cardiac arrest (1). One cat did not respond to treatment, and died 2 days after diagnosis.
A 24-year-old man presented to the emergency department with acute anticholinergic symptoms, hallucinations, and bizarre behavior following a large ingestion of diphenhydramine (Benadryl). Because of the large number of nonprescription preparations containing this antihistamine, similar ingestions are becoming increasingly frequent. Minor anticholinergic side effects associated with diphenhydramine are general medical knowledge. The effects of overdosage are less well known. The clinical presentation of toxic psychosis, its differential diagnosis, and its subsequent treatment are discussed.
Although the elimination of specific toxins by the removal of all plasma constituents is a crude approach, further refinements of the technique should permit safer and more selective detoxification in the future. Currently the mainstay of treatment of intoxicated patients remains careful, aggressive, supportive care. Plasmapheresis should be considered as yet an unproven, hazardous form of therapy for the treatment of intoxication. Its main role should be confined to a research setting in which investigators attempt to develop more advanced and potentially useful apheresis techniques. Membrane plasmapheresis with subsequent on-line treatment of the plasma by sorbent may remove specific plasma solutes. The plasma may be perfused back to the patient without the need to use replacement fluids, thus avoiding many of the side effects of conventional exchange. Bile acids have been removed by circulating plasma over charcoal-coated glass beads, and several toxic substances were shown to be absorbed by perfusion over amberlite resin columns. Another productive area for future research includes the use of plasma exchange therapy for the treatment of acute endogenous intoxications. Recent examples include the treatment of severe preeclampsia, extensive rhabdomyolysis, and life-threatening bleeding in a hemophiliac with inhibitors to clotting factors. Although plasmapheresis in the management of intoxications is still an experimental technique, it may open the door to the treatment of previously intractable syndromes, both medical and toxicologic.
The growing number of elderly in the United States will continue to increase the demand for emergency services. Although the emergency medicine core curriculum, as defined by the American College of Emergency Physicians, requires mandatory training in pediatrics, there is no mention of geriatric care. A special body of knowledge regarding normal aging as well as the special presentation of disease in the elderly is required to provide optimum care for the aged patient. We present an integrated geriatric curriculum designed to operate within a three-year emergency medicine residency program. This curriculum identifies specific educational objectives for training in geriatric emergencies that can be summarized as follows: identify those impairments and functional disorders that often complicate diagnosis and therapy; acquire an understanding of how physiologic changes in aging affect normal laboratory and radiologic values; develop knowledge of drug side effects and interactions in this population; understand and treat the group of disease peculiar to the elderly; recognize diseases and injuries that present a different clinical picture in old age; and differentiate and treat common psychosocial emergencies in the elderly. These educational objectives are further defined using a specific interlinked framework of didactic presentations, journal clubs, case conferences, therapeutic audits, formal rotations, and consultants. This format will provide valuable educational experiences for the emergency medicine resident and may strengthen positive attitudes toward geriatric medicine.
A 39-year-old women was admitted to the hospital following a large ingestion of a tricyclic antidepressant. The administration of magnesium citrate in repeated doses with activated charcoal resulted in a striking increase in serum magnesium levels followed by acute neuromuscular deterioration and respiratory depression. The patient required dialysis for control of hypermagnesemia. Her clinical condition improved slowly without further complication and she was discharged to a rehabilitation center.
An immunoglobulin negative material from the eluate of an anti-idiotype immunosorbent column [1] exhibited potent immunosuppressive activity. This material also inhibited the translation of globin mRNA in a cell-free reticulocyte lysate system. The translation inhibitory activity of this material was not attributable to nucleases which were separable by a blue-dextran agarose column. Further correlation between immunosuppressive activity and translation inhibitory activity was observed when GTP or GTP analogue was included in experimental systems. These results suggest that the immunosuppressive factor (or factors) may contain a translation inhibitory factor. The biochemical mechanism of immunosuppression is discussed.
The expression of class I major histocompatibility antigens was studied in six syngeneic adenovirus 12 (Ad12)-transformed LIS rat cell lines of varying tumorigenicity. The concentration of MHC class I product was estimated by indirect immunofluorescence staining of viable cells in suspension with specific antibody and cytofluorographic analysis, and by sensitivity to killing by allogeneic cytolytic T cells (CTLs) elicited by immunization with spleen cells in vivo and in mixed lymphocyte reactions in vitro. None of the rat cell lines examined was devoid of MHC class I antigen. When compared to syngeneic Ad2-transformed cells or fibroblasts, the average intensity of fluorescence of Ad12-transformed lines was lower, suggesting that the concentration of MHC class I antigen is somewhat lower in Ad12-transformed cells. Sensitivity to killing by both in vivo and in vitro induced allogeneic CTLs, however, was not markedly lower with Ad12-transformed cells and correlation was not found between tumorigenic potential in vivo and sensitivity to allogeneic T-cell killing in vitro.
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An operant conditioning apparatus for studies in equine pharmacology was constructed. Horses interacted with this apparatus by breaking a light beam and were rewarded with 30 ml of oats. Horses readily learned to use this apparatus and were trained to respond on a variable-interval-60 schedule. With this schedule, there was no direct relationship between the rate of light beam breaking and the reward. Horses thus developed their own individual response rates (ie, light-beam breaking rates), and these rates remained stable at between 5 and 35 responses/min for each horse over a period of months. The effects of 2 drugs on this paradigm were tested. Reserpine (5 mg/horse, IV) depressed the response rate in all horses tested. This depression was maximal between 3 and 5 days after treatment and lasted for up to 10 days. After small doses of cocaine (0.01 mg/kg of body weight IV), the response rate of 1 horse was stimulated, whereas 1 mg of cocaine/kg was required for maximal stimulation of response rate in another horse. Larger doses of cocaine inhibited response. Variable-interval response was a sensitive method of measuring drug effects in the horse and allowed accurate quantitation of drug effects that were not detectable by clinical observation.
(2'-5')(A)n synthetase is one of the mediators of interferon action. If activated by double-stranded RNA it converts ATP into pyrophosphate and (2'-5')(A)n. In turn, (2'-5')(A)n activates a latent endoribonuclease (RNase L) which cleaves single-stranded RNA. We report here the isolation and characterization of a homogeneous human (2'-5')(A)n synthetase. The enzyme was purified from interferon-treated HeLA S3 cells by chromatography of a ribosomal salt wash fraction on DEAE-cellulose, poly(I) . poly(C) agarose, and CM-cellulose. The purified (2'-5')(A)n synthetase can convert over 90% of ATP into (2'-5')(A)n. The enzyme is unstable but can be stabilized by certain nonionic detergents (e.g. Triton X-100). Its apparent Mr = 100,000, as determined by gel electrophoresis in sodium dodecyl sulfate, and about 80,000, as determined by centrifugation through a glycerol gradient. The human (2'-5')(A)n synthetase is similar to the corresponding enzyme from mouse Ehrlich ascites tumor cells, but differs from the latter in size (100,000 versus 105,000 daltons) and in ionic conditions required for maximal activity.
Published findings of intravenous nicotine self-injection indicate that the reinforcing properties of nicotine are weak when the drug is made available according to continuous reinforcement (CRF) or fixed-ratio (FR) schedules. CRF self-injection rates are generally only 2-3 times saline control levels and self-injection frequency is largely insensitive to changes in unit dose. In contrast, drugs of the psychomotor stimulant, opiate, and sedative-hypnotic classes, with similar pharmacokinetic parameters, maintain much higher self-injection rates and show systematic changes in rate with unit dose variations. Recent studies using interval and second-order schedules of nicotine presentation have been more successful in maintaining higher rates of self-administration behavior. Systematic dose-response functions have also been found under these conditions. Food-deprivation, species and strain differences, circadian rhythms, and duration of exposure to the drug also appear to be important variables in determining self-injection rate. Finally, the rapid development of tolerance to the effects of nicotine may account for changes in the pattern of self-administration within daily sessions and the differential sensitivity of those patterns to nicotine pretreatment.
The locomotor responses of horses given morphine and fentanyl were blocked or lessened by administration of naloxone or acepromazine. Naloxone given at the dosage of 0.015 mg/kg completely blocked the locomotor activity induced in horses given fentanyl (0.020 mg/kg of body weight). The locomotor stimulation produced by morphine given at the dosage of 2.4 mg/kg was reduced by 75% of naloxone (0.020 mg/kg). Acepromazine partially blocked the locomotor responses to fentanyl and morphine. This blockade activity reached its peak about 30 minutes after acepromazine was given (IV) and lasted more than 6 hours. Simultaneous administration of acepromazine and morphine was associated with substantial respiratory depression for more than 4 hours after administration of both drugs. In other experiments, fentanyl did not add to the partial locomotor response observed after large doses of pentazocine were given--this being consistent with the concept that pentazocine possesses both antagonist and agonist actions at the narcotic receptor. Furosemide and phenylbutazone, given at usually used clinical doses, had no effect on the locomotor response to fentanyl, indicating that the usual clinical dosages of neither drug exerted stimulant or depressant actions.
In horses given (rapid IV) methylphenidate (Ritalin, alpha-phenyl-2-piperidinacetic acid methyl ester; 0.70 mg/kg), plasma concentrations of the drug decreased rapidly at first, with an apparent alpha half-life of about 19 minutes, and then more slowly, with an apparent beta half-life of about 2.4 hours. These data were well fitted by a 2-compartment open model. In blood, about 40% of the methylphenidate present was in the plasma fraction, and of this, about 80% was plasma-protein bound. If given by subcutaneous or IM injection, plasma concentrations of methylphenidate peaked in about 1 hour and were no longer detectable (cleared) from plasma by 6 hours. Urinary clearance time, however, was longer, and between 12 and 24 hours should be allowed for a dose of methylphenidate to "clear" from urine. Using a variable-interval responding apparatus, methylphenidate was shown to stimulate the responding rate of horses up to 6 times above base line, making it the most potent central stimulant tested in this responding apparatus to date. Peak central stimulation at 30 minutes after IV dosing was seen in horses given 0.4 to 1.0 mg of methylphenidate/kg.
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