On-line medical command.
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Biomedical subjects
Publications and source records attributed to S J Davidson.
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Paramedics are often required to use on-line medical command (OLMC) when they provide advanced life support. We evaluated the efficacy of OLMC use under this broad patient inclusion rule and limited paramedic discretion. OLMC was associated with an average of an eight-minute longer on-scene time, and an infrequent rate of physician-directed deviation from written treatment protocols (3.7% of all OLMC calls). Of the system's advanced life support patients, 6.1% experienced changes in their prehospital health status, reflected in changes in the patient's level of consciousness. OLMC use was associated with improved health status in 5.5% of patients compared with 3.2% for those treated without OLMC (P = .1). The health status of 1.3% of the patients treated with OLMC deteriorated. This was not significantly different from the 1.1% of patients treated without OLMC whose status deteriorated. We suggest that targeted OLMC use with expanded paramedic discretion may improve the efficacy of OLMC. Further controlled comparative studies of OLMC efficacy under targeted OLMC use versus broad patient inclusion rules are needed.
Future heterosexual spread of HIV will in part depend on the efficiency of transmission from men to women and from women to men. We studied seventy-eight female sexual partners of men infected with HIV and 18 male sexual partners of infected women. Participants were interviewed concerning sexual practices, use of contraception and other risk factors for HIV infection. Fifteen out of 78 (19.2%) female partners and one out of eighteen (5.5%) male partners were seropositive for HIV antibody. All couples had practised vaginal intercourse. Seropositive female partners did not differ significantly from seronegative partners with regard to length of relationship, number of acts of vaginal intercourse, other sexual practices, stage of clinical disease in the index case, or numbers of other sexual partners in the last five years. In two women, seroconversion was documented after one act of unprotected sexual intercourse. The majority of infected female partners (eight out of 15) had sexual relationships with men who were asymptomatic and did not practice anal intercourse. Biological factors such as variability in infectivity of the index case and susceptibility of the contact, as well as behavioural variables may be important in determining transmission.
Heterosexual transmission of human immunodeficiency virus (HIV) was investigated in 123 subjects with no apparent risk factor for infection other than having had heterosexual intercourse with a person who was either infected with HIV or at high risk of being infected with it. Seven subjects were found to be infected with the virus. Risk factors for transmission included being the regular sexual partner of an abuser of intravenous drugs and having a sexual relationship of more than 18 months' duration. Anal intercourse was not a risk factor in the three subjects who admitted to it. There were 41 regular partnerships with abusers of intravenous drugs in which the antibody state and history were fully known for both partners. In these partnerships male to female transmission of the virus occurred in five out of 34 (15%) and female to male in one out of seven. In 30 couples in whom one partner was known to be positive for HIV and an abuser of intravenous drugs four female partners were found to be seropositive at first testing, but there were no new positive results on subsequent serial testing. In six of these 30 couples both partners abused intravenous drugs but the partner who was negative for HIV remained so. Few of the partnerships always practised safe sexual techniques, even after a partner was known to be positive for HIV. Heterosexual transmission of HIV occurred but was incomplete and may be related to the timing of the relationship with the infection.
During 1985 many drug abusers who lived in Edinburgh were found to be infected with the human immunodeficiency virus (HIV). As a result an alternative counselling and screening clinic for testing for antibodies to HIV was established for use by drug abusers. Four hundred and forty one patients were counselled in the first year, and over 60% were either drug abusers or their sexual contacts. One hundred and fourteen (26%) patients were positive for HIV antibody, and 100 (88%) of these were current or former drug abusers. The HIV seropositivity rate in drug abusers was 52% but was only 7% in their sexual contacts. Services were provided for these people as well as counselling before and after the test. The cost of this counselling service for the first year was 27,000 pounds or 61.22 pounds per patient. The unexpected mobility of 23% of the Edinburgh drug abusers, particularly to other areas of Britain, suggests that similar services need to be set up elsewhere.
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Long-term effects of phenobarbital on behavior and learning, persisting after drug withdrawal, have not been defined. To look for such effects on the developing nervous system, we treated albino rat pups with phenobarbital for 30 days and then tested them at intervals starting 10 days after the cessation of drug therapy. Beginning at age 6 days, 12 pups were given Ph subcutaneously, gradually increasing the dose to 30 mg/kg/dose b.i.d. by 11 days and continued until 36 days. Twelve control pups were injected with saline. Serum phenobarbital concentrations at 16 days were 54 to 32 micrograms/ml and at 31 days 36 to 4 micrograms/ml. From 46 to 55 days, all animals were tested in a water T maze. The experimental animals completed the four daily runs faster than controls (P = 0.003), made fewer errors (P = 0.003), and spent less time on error-free runs (P = 0.04). When the same animals were retested in the maze at 129 to 136 days, the trend toward faster times was not significant. There were no differences in brain weights of experimental and control rats at 157 days. Twelve pups treated similarly with phenobarbital at 20 mg/kg/dose b.i.d. spent less time on error-free runs than 12 controls when tested at 48 to 57 days of age (P = 0.05) but no differences were found when 12 similarly treated pups were tested at 79 to 85 days. There were no differences in brain weights of the treated and control rats at 78 days of age. Thus it was shown that phenobarbital administration in suckling rats had an effect on behavior that was present 10 to 20 days after the drug was cleared from their serum.
Many medical schools have required emergency medicine courses for freshmen medical students, usually through participation in BLS (basic life support) or EMT activities. For several years students at our institution have participated in a required emergency medical technician-ambulance grade (EMT-A) course. While retaining much of the material presented in that original EMT-A course, the course has now been expanded to serve as the medical students' introduction to clinical medicine. This expansion resulted from the belief that emergency medicine provides initial patient contact in the presence of a faculty uniquely suited to introduce the broad domain of clinical medicine to the medical student. Emergency physicians, more than any other specialists, must possess the ability to obtain an incisive history promptly, perform an accurate physical examination, and arrive at an assessment with limited laboratory and radiologic data. Initial access to the clinical education of medical students provides the opportunity to direct their efforts in a prioritized fashion, and thus helps to organize their thought processes for further development as clinicians. Departments of emergency medicine should be willing to accept this incremental responsibility for the introduction of the medical student to the clinical and laboratory assessment of patients.
8-methoxypsoralen, the most widely used psoralen in photochemotherapy, was shown to induce mixed-function oxidases. Induction of mixed-function oxidases in mouse liver was examined after mice were given a single dose of one of three psoralens. 8-methoxypsoralen clearly induced p-nitroanisole O-demethylase and slightly induced aryl hydrocarbon hydroxylase. Psoralen and 4,5',8-trimethylpsoralen failed to induce either enzyme. These results represent the first enzyme induction studies on these clinically useful compounds. The studies may have relevance in understanding the clinical differences in skin photosensitizing activity and photochemotherapeutic effectiveness of the compounds in such diseases as psoriasis and vitiligo.
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Degradation of exogenous [125I] ribonuclease by renal lysosomes follows first-order kinetics in ribonuclease concentration. To demonstrate this, it was necessary to apply corrections for the presence of labeled but digestively inactive particles, either pinocytic vesicles or lysosomes damaged during preparation. Such kinetics were not observed under conditions favoring lysosomal breakdown, i.e., in isotonic KCl, or in the absence of EDTA. The kinetic analysis allows determination of half-times for lysosomal protein digestion. This facilitates comparison of different lysosome preparations, or of in vitro degradation rates with results of in vivo metabolism studies. Degradation of [125I] ribonuclease showed a half-time of about 11 1/2 minutes in isotonic sucrose or saline media. This is less than the half-time for decrease of kidney radioactivity in vivo after uptake of [125I] ri-onuclease. The proportion of exogenous, labeled protein contained within secondary lysosomes was determined as a function of time after injection of ribonuclease, to monitor transfer of the protein from pinocytic vesicles to lysosomes. Ribonuclease molecules remained in pinocytic vesicles for approximately three minutes after uptake, before passage into the lysosomes.
In previous studies, in vitro digestion of [1 2 5-I] ribonuclease by lysosomes of mouse kidney was limited because breakdown, which was rapid at first, slowed markedly so that most of the labeled protein escaped degradation. We now describe incubation conditions which allow digestion to proceed until approximately 70% of the exogenous protein label is released in acid-soluble form, after 30-45 min at 37 degrees C. Such activity is seen with either the addition of EDTA or incubation of concentrated cell particle suspensions. EDTA is effective in low concentrations and shows the same stimulation of digestion over a range of approximately 10-minus 6--10-minus 3 M. Other chelating agents have similar effects; dipyridyl and hydroxquinoline are as effective as EDTA, o-phenanthroline and diethyldithiocarbamate are slightly less effective. When the incubation medium had been treated with a chelating resin, Chelex 100, dilute suspensions of lysosomes were as active as those in EDTA. These results lead to the conclusion that metal ions, present as contaminants in very small concentrations, inhibit the activity of mouse kidney lysosomes. The effect of the metal ions is to diminish lysosomal stability, leading to release of intact labeled ribonuclease in non-sedimentable form. Interaction between lysosomes and metal, leading to inhibition of digestion upon heating, occurs at low temperature, but breakdown requires incubation at 37 degrees C and may be autolytic. In contrast to chelators, mercaptoethanol is without marked effect on stability; the stimulation in digestion rate caused by this agent is due either to a direct effect on the lysosomal enzymes or to a non-destructive influence on the lysosomal structure.
Preparations of radioactive lysosomes were obtained from mouse kidney after injection of radioactive iodine-labeled bovine ribonuclease. Stability of these lysosomes in various media was estimated from measurements of proteolytic activity towards the ribonuclease, and of ribonuclease retention in particles. The lysosomes were stable at 37 degrees C in isotonic, sucrose-free solutions of KCl, NaCl, and potassium acetate, and in mixtures of these with MgCl2, showing that these salts are relatively impermeant through the lysosomal membranes. The membranes were less permeable to Na+ than to K+. Both KCl and NaCl exerted their optimal protective effects over a broad concentration range above 0.125 M in 0.025 M acetate buffer. Mg2+ enhanced the protective effect of both K4 and Na+; the osmotic effect of 0.075 M NaC1-0.05 M MgCl2 was indistinguishable during the entire course of ribonuclease digestion from that of isotonic sucrose. Osmotic protection by KC1-MgC12 was demonstrated over the H range5.5-7.0. A marked alteration in membrane properties occurs at lower temperatures in 0.11 M KC1-0.01 M MgCl2 such that, at 0 degrees C, K+ permeability is much higher than at 37 degrees C, as shown by a several-fold decrease in stability at the lower temperature.