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Biomedical subjects

R F Clark

Publications and source records attributed to R F Clark.

At least 19 recordsLinked to original sources
PubMed1992

Heterochromatin protein 1, a known suppressor of position-effect variegation, is highly conserved in Drosophila.

The Su(var)205 gene of Drosophila melanogaster encodes heterochromatin protein 1 (HP1), a protein located preferentially within beta-heterochromatin. Mutation of this gene has been associated with dominant suppression of position-effect variegation. We have cloned and sequenced the gene encoding HP1 from Drosophila virilis, a distantly related species. Comparison of the predicted amino acid sequence with Drosophila melanogaster HP1 shows two regions of strong homology, one near the N-terminus (57/61 amino acids identical) and the other near the C-terminus (62/68 amino acids identical) of the protein. Little homology is seen in the 5' and 3' untranslated portions of the gene, as well as in the intronic sequences, although intron/exon boundaries are generally conserved. A comparison of the deduced amino acid sequences of HP1-like proteins from other species shows that the cores of the N-terminal and C-terminal domains have been conserved from insects to mammals. The high degree of conservation suggests that these N- and C-terminal domains could interact with other macromolecules in the formation of the condensed structure of heterochromatin.

Amino Acid Sequence↗
PubMed1992

Optimal patient position for transport and initial management of toxic ingestions.

STUDY OBJECTIVES: Many factors influence the rate of gastric emptying and therefore the rate of drug absorption in the orally poisoned patient. Limited studies have evaluated the effect of body position on the rate of gastric emptying of radiographically marked foods and contrast media, but effects on drug absorption have not been studied previously. Our hypothesis was that body position would have an effect on the rate of drug absorption in an oral overdose model. DESIGN: A blinded, within-subjects (crossover) design. PARTICIPANTS: Six male and six female healthy, adult volunteer subjects with no concurrent drug use or medications affecting gastrointestinal function. INTERVENTIONS: Five body positions commonly used in prehospital and emergency department settings were examined: left lateral decubitus, right lateral decubitus, supine, prone, and sitting. All were performed by all subjects in random order with a three-day washout phase between trials. To simulate an acute overdose, fasted subjects ingested 80 mg/kg acetaminophen in the form of 160-mg pediatric tablets. Each subject then remained in the body position for that trial for two hours. Acetaminophen levels were obtained at 15-minute intervals, and a two-hour area under the curve (AUC) was calculated for each subject trial to represent total drug absorption during each study period. Investigators were blinded to all results until all trials were completed. MEASUREMENTS AND MAIN RESULTS: All subjects completed the study. Group mean drug absorption as represented by two-hour AUC (mg.L.min) was calculated for each body position. AUC for left lateral decubitus (6,006 +/- 2,614) was lowest but did not significantly differ from that for supine (6,649 +/- 2,761). Both were significantly less than those for prone (7,432 +/- 1,809), right lateral decubitus (8,950 +/- 1,405), and sitting (8,608 +/- 1,725) positions (P less than .05 by one-way analysis of variance and follow-up paired t tests). CONCLUSION: Initial drug absorption as determined by two-hour AUC was lowest in the left lateral decubitus position. Although the difference between the left lateral decubitus and supine positions did not reach statistical significance, both left lateral decubitus and supine were significantly lower than three other common patient body positions tested. Because the left lateral decubitus position has other advantages (eg, prevention of aspiration) in addition to minimizing drug absorption, we recommend that orally poisoned patients be placed in the left lateral decubitus position for prehospital and initial ED management.

Acetaminophen↗
PubMed1992

Massive diphenhydramine poisoning resulting in a wide-complex tachycardia: successful treatment with sodium bicarbonate.

Diphenhydramine poisoning is characterized most often by anticholinergic effects. Cardiotoxicity and circulatory collapse have rarely been reported after massive ingestions of diphenhydramine and other H1-receptor-blocking agents, although these substances have local anesthetic properties and have been studied as antiarrhythmics. We report the case of a patient who developed a wide-complex tachycardia as a complication of acute diphenhydramine poisoning that responded to IV sodium bicarbonate.

Adolescent↗
PubMed1992

Clinical presentation and treatment of black widow spider envenomation: a review of 163 cases.

STUDY OBJECTIVE: To review cases of black widow spider envenomation to describe the clinical presentation and evaluate the efficacy of treatment. DESIGN: Retrospective chart review. SETTING: An urban toxicology referral center. TYPE OF PARTICIPANTS: All patients attended by the toxicology service and discharged from our hospital between January 1982 and December 1990 with a diagnosis of black widow spider envenomation. INTERVENTIONS: Inclusion criteria were either a positive black widow spider identification or a visible envenomation site ("target lesion"). Depending on the clinical presentation, patients were categorized as grade 1, 2, or 3 in severity. The efficacy and side effects of treatment alternative were evaluated. MEASUREMENTS AND MAIN RESULTS: One hundred sixty-three patients met the inclusion criteria. The most common sites of envenomation were the upper and lower extremities. The most common presenting complaint was generalized abdominal, back, and leg pain. One hundred eighteen patients initially presented to our institution, and 45 were transfers. Pain relief of grade 2 and 3 envenomations was achieved most effectively with either black widow spider-specific antivenin alone or a combination of IV opioids and muscle relaxants. Fifty-eight patients received antivenin with complete resolution of symptoms in a mean time of 31 +/- 26.7 minutes. Of the 118 patients initially seen at our institution, the mean total duration of symptoms was 9 +/- 22.7 hours in patients receiving antivenin and 22 +/- 24.9 hours in patients not receiving antivenin. Fifty-two percent of patients not receiving antivenin required hospitalization, whereas only 12% of those receiving antivenin were admitted. One patient died of severe bronchospasm after receiving antivenin. Calcium gluconate was not effective in providing symptomatic relief in this series, with 96% of the grade 2 and 3 envenomations treated initially with calcium gluconate requiring the addition of IV opioids or other analgesics for symptomatic relief. Fifty-five percent of patients initially receiving IV morphine and 70% of those initially receiving both IV morphine and benzodiazepines obtained symptomatic relief without additional medication. CONCLUSION: One hundred sixty-three envenomations by black widow spiders were reviewed and graded according to severity with treatment modalities evaluated. Although calcium gluconate usually has been considered the first-line treatment of severe envenomations by black widow spiders, we found it ineffective for pain relief compared with a combination of IV opioids and benzodiazepines. The use of antivenin significantly shortened the duration of symptoms in severe envenomations.

Adolescent↗
PubMed1992

Eligibility for publicly financed home care.

OBJECTIVES: Proposals for publicly financed home care for the elderly now tend to include cognitive impairment criteria as well as activities of daily living (ADL) criteria. The numbers of elderly deemed eligible for services will depend on the definitions of ADL and cognitive impairment used. METHODS: Data from the 1984 National Long-Term Care Survey were used to generate a series of estimates of the community-dwelling elderly with ADL disabilities and cognitive impairment. RESULTS: When only ADL criteria are used, estimates of disability range from 472,000 to over 3 million (1.6% to 12.5% of the community-dwelling elderly). These estimates increase to approximately 1 million to 4.2 million (3.5% to 14.0% of the community-dwelling elderly) when cognitive impairment criteria are added. CONCLUSIONS: The use of more stringent or more liberal eligibility criteria will have dramatic effects on the number of elders who qualify for services. The nature of the eligibility criteria employed in any expansion of federally financed home care benefits will be a major factor in determining the costs of such a program.

Activities of Daily Living↗
PubMed1991

Toxicology screening of the trauma patient: a changing profile.

STUDY OBJECTIVES: To determine the current ingestants found in the multiply injured trauma patient and to determine if this select group of ingestants affected the resuscitation, evaluation, or convalescent management of these patients. DESIGN: A one-year retrospective analysis was performed on all patients who were admitted to an urban trauma center with a discharge diagnosis of multiple trauma and who received a comprehensive toxicology screening test. MAIN RESULTS: One hundred twenty-seven of the 177 patients (72%) who fulfilled the criteria had positive toxicology screens. Ethyl alcohol was the only drug present in 26 of these patients (20%); 57 (45%) were positive for drugs other than ethyl alcohol. A combination of ethyl alcohol and at least one other drug was quantified in 44 patients (35%). The most often encountered substances were ethyl alcohol (55%), marijuana (24%), and cocaine (21%). Twelve drug screens (9%) demonstrated pharmaceuticals (eg, acetylsalicylic acid, acetaminophen, or cyclic antidepressants) that may require specific antidotal treatment. CONCLUSION: The ingestant profile found in this subgroup of trauma patients differed from those of previous studies. Although a select group of these ingestants requires specific treatment or affects the physical assessment of the patient, none of these trauma patients received more than supportive care.

Emergencies↗
PubMed1991

Transplacental transport of N-acetylcysteine in an ovine model.

STUDY OBJECTIVE: Acetaminophen freely crosses the placenta, and acetaminophen ingestion is the most frequent intentional overdose in pregnancy. Although most patients do well after maternal treatment with the antidote N-acetylcysteine (NAC), fetal death with massive hepatic necrosis has occurred. It has never been shown whether NAC crosses the placenta to yield fetal plasma levels equal to those associated with hepatoprotective effects in human beings. Our study objective was to evaluate this in a widely accepted large animal model for maternal-fetal research. DESIGN AND TYPE OF PARTICIPANTS: A nonblinded experiment was performed using four domestic sheep at near-term gestation. INTERVENTIONS: NAC 150 mg/kg IV was administered to the ewe over 15 minutes. After induction of anesthesia, the fetal head was delivered surgically and a neck vein cannulated for blood sampling. Maternal and fetal blood samples were obtained at the end of NAC infusion, at 30- and then at 60-minute intervals for four hours. Plasma NAC levels were determined by gas chromatography/mass spectroscopy (detection limit, 2 micrograms/mL; quantification limit, 5 micrograms/mL). RESULTS: Maternal peak plasma NAC levels were 619, 631, 1,757, and 2,512, micrograms/mL, respectively, within 30 minutes of infusion. However, NAC was only minimally detectable in plasma of two fetal animals and transiently reached quantifiable levels in two others. None of the fetal animals attained serial plasma NAC levels that equalled those associated with therapeutic dosing or hepatoprotective effects in human beings. CONCLUSION: Transplacental transport of NAC is clinically insignificant in a mammalian model resembling the human being. These findings suggest that the human fetal liver is not protected from acetaminophen toxicity by maternal NAC therapy.

Acetylcysteine↗
PubMed1991

Digoxin-specific Fab fragments in the treatment of oleander toxicity in a canine model.

STUDY OBJECTIVE: To examine the efficacy of digoxin-specific Fab fragments (dsFab) in the treatment of experimentally induced Nerium oleander cardiac glycoside toxicity in a dog model. DESIGN: A nonblined, placebo-controlled experiment. SUBJECTS: Ten adult greyhound dogs of either sex divided into treatment and control groups of five dogs each. INTERVENTIONS: A tincture of oleander was prepared and administered intravenously to each animal. After the onset of cardiotoxicity, the treatment group received 60 mg/kg dsFab IV. MEASUREMENTS AND MAIN RESULTS: All dogs exhibited dysrhythmias meeting our criteria for cardiac glycoside cardiotoxicity within 27 minutes of beginning the infusion. Three of five control dogs had lethal dysrhythmias during the three-hour observation period. The remaining two control dogs exhibited dysrhythmias throughout the three-hour experiment. All five of the dsFab-treated dogs survived and converted to normal sinus rhythm within eight minutes of dsFab infusion. Three treatment animals reverted back to nonlethal and hemodynamically stable dysrhythmias after a mean of 107 minutes. CONCLUSION: Large doses of dsFab are efficacious in the treatment of dysrhythmias in this canine model of N oleander cardiac glycoside poisoning.

Animals↗
PubMed1991

Preferential distribution of active RNA polymerase II molecules in the nuclear periphery.

We have combined immunogold labeling with the Miller spreading technique in order to localize proteins at the electron microscope (EM) level in whole mount nuclei from mouse and human fibroblasts. Anti-histone H1 antibody labels nuclei uniformly, indicating that the nuclear interior is accessible to both antibodies and gold conjugates. Anti-topoisomerase I antibody labels nucleoli intensely, in agreement with previous immunofluorescent and biochemical data. Two different antibodies against the large subunit of RNA polymerase II (pol II) show preferential labeling of the nuclear periphery, as do antibodies against lamin, a known peripheral nuclear protein. Treatment of cells with alpha-amanitin results in loss of virtually all RNA polymerase II staining, supporting the specificity of labeling. Finally, when nuclei are incubated in the presence of biotin-UTP (bio-UTP) under run-off transcription conditions, incorporation is preferentially located at the nuclear periphery. These results support the conclusions that transcriptionally active pol II molecules are non-uniformly distributed in fibroblast nuclei, and that their differential distribution mirrors that of total pol II.

Amanitins↗
PubMed1990

Marijuana.

Marijuana remains a complex, poorly understood drug with many effects. Although its acute psychological effects are well described, data linking cannabis use to chronic psychiatric or social problems and decreased driving or workplace safety are much less clear. Current laboratory procedures have not yet been shown useful to demonstrate acute intoxication, so they remain screening instruments for those interested in detecting cannabis use for other reasons. Although both acute and chronic effects of marijuana use have been described, they appear to be less than other commonly abused substances, including tobacco and alcohol. The rare acute complications that present to the Emergency Department can be managed with conservative measures.

Ambulatory Care↗
PubMed1990

Treated vs reported toxic exposures: discrepancies between a poison control center and a member hospital.

Statistics accumulated by Poison Control Centers (PCC) are routinely used on the local, regional and national levels by governmental agencies to set policy and direct funding. Incomplete reporting by member hospitals is recognized by PCC as a factor contributing to discrepancies in epidemiological estimates; however little emphasis is classically placed by the PCC on expanding reporting from member hospitals. A 1y retrospective review of patients with toxic exposure presenting to an urban Emergency Medicine Department (EMD) was performed to quantify the lack of concordance between treated and reported toxic exposures. 470 toxic exposures presented over the study period, of which only 123 (26%) were relayed to the regional PCC. Inhalation exposures were least likely to be referred for PCC consultation (3%); whereas PCC consultation was obtained for 33% venomous snake bite cases, and 95% of the cyclic antidepressant ingestions. Clusters of similar exposures resulted in fewer PCC consultations. Understanding each hospital's "profile" for handling toxic exposures, and individualized advertisement by the PCC to their member hospital may increase their data reporting. The statistical significance of their epidemiological studies as well as their revenue may increase.

Environmental Exposure↗