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S J Davidson

Publications and source records attributed to S J Davidson.

49 records · Page 3Linked to original sources

Induction of mixed-function oxidases in mouse liver by psoralens.

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.

Administration, Oral↗

Proteolytic activity within lysosomes and turnover of pinocytic vesicles. A kinetic analysis.

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.

Animals↗

Metal-ion effects on proteolysis and stability in secondary lysosomes of mouse kidney.

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.

Animals↗

A thermally induced alteration in lysosome membranes: salt permeability at 0 and 37 degrees C.

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.

Animals↗

Patient-initiated refusals of prehospital care: ambulance call report documentation, patient outcome, and on-line medical command.

INTRODUCTION: There is a growing interest in cases in which emergency medical services (EMS) providers evaluate a patient, but do not transport the patient to a hospital. A subset of these cases, the patient-initiated refusal (PIR) in which the patient refused care and transport, was studied and evaluated. The objectives of the study were to examine the adequacy of ambulance call report documentation in PIR, to examine the clinical outcome of these patients in one hospital-based, suburban EMS system, and to assess the potential impact of on-line medical command (OLMC) on cases of PIR. METHODS: The system studied is a hospital-based, transport-capable, advanced life support service in a suburban EMS system, with an annual call volume of 4,200 runs. During the 6-month study period, all ambulance call reports completed by the paramedics and medical command control forms completed by medical command physicians were examined, and cases of PIR collected. Each ambulance call report was examined for adequacy of documentation. Patient outcome was determined from emergency department records and telephone follow-up. RESULTS: Eighty-five PIRs were documented during the study period. Four cases were excluded because of a missing ambulance call reports and/or medical command control forms, leaving 81 PIRs for analysis. Despite policy requiring OLMC in cases of PIR, OLMC was established in only 23 PIRs (28%). Of these, two (9%) had inadequate ambulance call report documentation. Of the 58 PIR in which OLMC was not established, 25 (43%) had inadequate ambulance call report documentation (p < 0.001, Fisher's exact test). Follow-up was obtained for 54 (67%) PIR. Of these, 37 (68%) did not subsequently see a physician, and all needed no further medical care. Seven (13%) saw their own physicians within a few days of the initial refusal of prehospital care, and had no further problems. Ten patients were seen in an emergency department within a few days. Three (6%) were discharged, and did well. Seven (13%) were admitted to the hospital, with four (7%) admitted to monitored beds, and three (6%) to unmonitored beds. There were no deaths. CONCLUSIONS: Ambulance call report documentation is better with OLMC than without. Patients who initially refuse care may be ill, and some ultimately will be hospitalized. Further research may elucidate a role for OLMC in preventing refusals by incompetent patients, convincing patients who are competent but appear ill to accept transport, and assisting paramedics with other difficult or unusual circumstances.

Adult↗

Hazardous materials preparedness in the emergency department.

INTRODUCTION: This study was conducted to examine the preparedness of emergency departments (EDs) to safely receive, decontaminate, and treat chemically contaminated patients. METHODS: The safety officers of all 58 acute-care hospitals in the five-county philadelphia metropolitan region were surveyed by mail, with a repeat mailing to nonresponders followed by telephone contact. The 16 survey questions addressed the ability of EDs to safely decontaminate and treat chemically contaminated patients. RESULTS: Thirty-eight of 58 hospitals (66%) returned usable surveys. Of these, 24 (63%) have a written plan for decontamination and treatment of chemically contaminated patients in the ED, and 19 (50%) have a hospital-wide disaster plan that includes contingencies for decontamination and treatment of one or more chemically contaminated patients. Thirteen hospitals (34%) conducted a drill of either of these plans in 1994. Twenty (53%) EDs have a specific treatment area for chemically contaminated patients. A stock of supplies for protecting the ED from secondary contamination is maintained by 16 (42%). While 24 (63%) store personal protective equipment, most of these involve only gowns, gloves, and surgical masks; only 13 provide any type of respiratory protection. Nine respondents were certain that patients brought in by local EMS would have been adequately decontaminated in the field, eight stated that they believed or felt decontamination would be adequate, and 12 were concerned that field decontamination might not be adequate. Eighteen hospitals (47%) reported treating one or more chemically contaminated patients in 1994. The authors believe the return rate reflects reluctance to commit hospital policies to paper. This was confirmed during telephone follow-up of nonrespondents when, for example, one safety officer discussed hazardous materials (hazmat) principles for 40 minutes, but refused to complete the survey. CONCLUSIONS: Hospital hazmat preparedness in this area varies tremendously. A significant proportion of hospitals lack a written plan and equipment to allow the ED to safely and effectively handle the chemically contaminated patient. There is reluctance to discuss this topic.

Data Collection↗

Legislative and regulatory description of EMS medical direction: a survey of states.

OBJECTIVE: To assess regulatory trends in EMS medical direction by examining state EMS legislation and regulations, and legal qualifications for medical direction. METHODS: A two-page survey was mailed to all 50 state EMS directors, with a repeat mailing to nonresponders and telephone follow-up as needed. Copies of EMS legislation and regulations were requested to assist in the interpretation of answers to survey questions. The questions focused on two physician roles in the oversight of the practice of paramedics; off-line ALS service medical director (ASMD) and on-line medical command (OLMC). RESULTS: Thirty-nine surveys were returned (78%). Only one state (IL) requires that ASMDs be board-certified in emergency medicine. Thirteen others (33%) permit physicians with primary care specialization or various ACLS/ATLS certifications to serve as ASMDs. Twenty-two states (56%) require only that the ASMD be a physician; three states (8%) have no requirements at all. Eight states (21%) have no requirements for personnel providing OLMC, and another 25 (64%) require only physician licensure. Six states (15%) require various ACLS/ATLS certifications. Several states do not differentiate between the two physician roles. Twenty-four states (62%) provide some type of Good Samaritan protection for medical direction, but in two of these only unpaid medical directors are protected. CONCLUSIONS: There is tremendous variation in regulatory requirements for physician participation in EMS medical direction activities at the ALS level. Few states have specific training or background requirements for the provision of OLMC, and a requirement for board certification in emergency medicine is the exception, not the rule.

Certification↗