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Biomedical subjects

S M Schneider

Publications and source records attributed to S M Schneider.

At least 19 recordsLinked to original sources

Retinoids control the expression of c-erbB receptors in breast cancer cells.

Nuclear retinoid and membrane c-erbB receptors participate in signal transduction systems that control mammary epithelial cell proliferation and differentiation. Recently, we demonstrated that c-erbB receptor activation stimulates retinoic acid receptor-alpha expression. We now report that retinoids reduce SK-BR-3 breast cancer cell growth by inhibiting the cell cycle and by inducing apoptosis. This is accompanied with reduced c-erbB expression as determined by FACS, Western, Northern, RT-PCR, and reporter assays. All-trans (ATRA) and 9-cis retinoic acid (9cRA) reduce c-erbB-1 protein to 50-100%, c-erbB-2 to 20-30%, and c-erbB-3 to 10-50% of control, depending on the concentration, respectively, without influencing the tyrosine phosphorylation status. Down-regulation of c-erbB-2 and -3 was seen at all levels analyzed, whereas c-erbB-1 mRNA remained unchanged. Retinoic acid-mediated down-regulation of growth and c-erbB-2 and -3 expression was also seen in MCF-7 cells. We conclude that retinoic acids are efficient repressors of c-erbB-2 and -3 gene expression, whereas c-erbB-1 is not markedly affected.

Alitretinoin

Effects of retinoic acid and fenretinide on the c-erbB-2 expression, growth and cisplatin sensitivity of breast cancer cells.

We investigated the effects of all-trans retinoic acid (ATRA) and fenretinide (4-HPR) on c-erbB-2 expression in SK-BR-3, BT-474 and MCF-7 breast cancer cells and on the growth, differentiation, apoptosis and cisplatin (CDDP) sensitivity of SK-BR-3 cells. It has been reported that oestrogen inhibits c-erbB-2 in oestrogen receptor-positive breast cancer cells. Using ELISA, Western and Northern analysis we have demonstrated that ATRA and 4-HPR exert similar effects down-regulating c-erbB-2 protein and mRNA in c-erbB-2-overexpressing SK-BR-3 and BT-474 and in normally expressing MCF-7 cells. Both retinoids inhibit SK-BR-3 cell growth. ATRA induces cellular enlargement and flattening, suggesting epithelial differentiation. 4-HPR causes nuclear and cytoplasmic condensation, DNA fragmentation and externalization of phosphatidylserine, indicating apoptosis. c-erbB-2 expression/activity has been linked to sensitivity against CDDP. Therefore, combinations of ATRA or 4-HPR with CDDP were tested for their anti-proliferative activity. Retinoid-conditioned cells were either exposed to retinoid and CDDP (schedule I, 'continuous retinoid treatment') or to CDDP alone (schedule II, 'retinoid pretreatment'). This retinoid-conditioning followed by CDDP +/- retinoid yields stronger growth inhibition compared with unconditioned cells, which were exposed to CDDP +/- retinoid (schedule III, 'no retinoid pretreatment'). The inefficacy of schedule III indicates that retinoid-conditioning is essential for the improvement of the antiproliferative effect. The interactions in schedules I and II are synergistic for ATRA and CDDP, but slightly antagonistic for 4-HPR and CDDR However, 4-HPR + CDDP is more effective in growth inhibition than each drug alone.

Antineoplastic Combined Chemotherapy Protocols

Gatekeepers: a missed opportunity for safe transport.

OBJECTIVE: To assess whether contact with a health care provider or gatekeeper increases the use of an ambulance for patients with acute chest pain. METHODS: A convenience sample of adults > or =40 years of age presenting with a chief complaint of chest pain were interviewed by trained personnel regarding transport used to come to the ED. The study was performed at the ED of an urban university hospital. Patients with hemodynamic instability and those receiving thrombolytics or emergency angioplasty were excluded. Patients were asked about access to a primary health care provider and contact with a provider regarding this ED visit, including instructions given for transportation. RESULTS: Of the 450 interviewed patients, 42% arrived by ambulance. Those who had contact with a health care provider prior to the ED visit were less likely to come by ambulance than those without contact, 31% vs 51% (p < 0.001). Of the patients who had cardiac enzymes obtained to work up for their chest pain, 34% with health provider contact vs 57% without health provider contact arrived by ambulance (p < 0.001). Of those with acute myocardial infarction, 30% with health provider contact vs 66% without health provider contact came by ambulance (p < 0.03). Patients who recalled transport instructions from their providers tended to follow those instructions. The majority of patients who recalled no specific transport instructions arrived by personal automobile. CONCLUSION: Of patients presenting to an ED for evaluation of chest pain, those who made contact with a health care provider were less likely to arrive via ambulance.

Adult

Definition of emergency medicine.

This SAEM position paper clarifies the role of emergency medicine in health care delivery. It builds upon the working definition of emergency medicine developed by the American College of Emergency Physicians in 1994 by describing the health care role of emergency physicians (EPs). EPs are first-contact providers who care for all patients regardless of age, gender, time of presentation, or ability to pay. They remain the only continuously accessible specialty for patients seeking help and solace in the health care system. They are an essential link in the health care continuum between primary care physicians, specialists, the out-of-hospital system, the patient, inpatient services, and communication services. The EP's role is in organizing and monitoring the emergency care delivery system. Part of this role is to better align the health care provider training and ability with the specific medical needs of a patient. The emergency health care system remains the essential medical safety net for all individuals needing care in this country.

Emergency Medicine

Tyrosine kinase signaling pathways control the expression of retinoic acid receptor-alpha in SK-BR-3 breast cancer cells.

Breast carcinomas are frequently characterized by hyperactivated c-erbB receptor tyrosine kinase signaling. Combination of anti-proliferative retinoids with growth-inhibitory c-erbB-specific agents might induce therapeutic benefit. We demonstrate close interactions between the c-erbB and the retinoic acid receptor system in SK-BR-3 breast cancer cells. Epidermal growth factor and heregulin-beta1 activate c-erbB receptors and dose- and time-dependently up-regulate retinoic acid receptor-alpha (RAR-alpha) mRNA. Similar effects have been found for the growth-inhibitory c-erbB-2 receptor tyrosine kinase-activating antibody 4D5 and the tyrosine phosphatase inhibitor orthovanadate. In contrast, the tyrosine kinase-inhibitor herbimycin A reduces tyrosine-specific protein phosphorylation and down-regulates RAR-alpha. Our data demonstrate that the expression of RAR-alpha, which represents a key mediator of the anti-proliferative effects of retinoids in breast cancer cells, is regulated by modulators of tyrosine kinase signaling. The levels of RAR-beta and -gamma mRNAs, however, are not affected by such agents.

Breast Neoplasms

Cocaine balloon aspiration: successful removal with bronchoscopy.

Ingestion of balloons containing illicit substances along with the potential toxic sequelae associated with these ingestions have been described in the literature. This report describes the successful bronchoscopic retrieval of a cocaine balloon after aspiration. A 39-year-old man was witnessed swallowing several balloons that were thought to contain heroin. Shortly after ingestion, the patient became unconscious and required nasotracheal intubation. Before intubation, several balloons were removed from the oropharynx. Naloxone 4 mg was administered en route to the emergency department (ED). Following naloxone, the patient awoke and became agitated and combative. On arrival in the ED, midazolam, succinylcholine, and vecuronium were required to manage his combativeness. Vital signs were: heart rate, 130 beats/min; blood pressure, 128/86 mm Hg; respirations, 12 breaths/min; temperature, 96.5 degrees F. A balloon and balloon tip were removed during lavage. Whole bowel irrigation with a polyethylene glycol electrolyte solution was initiated. A right upper lobe infiltrate was identified on chest X-ray and aspiration of a balloon was suspected. At bronchoscopy, a small yellow, intact balloon visualized in the basilar segment of the right lower lobe was removed. Toxicologic analysis of the balloon contents found cocaine. The rest of the patient's hospital course was unremarkable and he was discharged 5 days after admission. This case brings to light the potential concerns, such as respiratory compromise, associated with aspiration of small balloons in the body stuffer. Additionally, the potential for the development of toxicity if the balloon ruptures and toxin absorption occurs through through the lungs should be considered. Emergency physicians and toxicologists should be aware of this significant complication of packet ingestion in the body packer or stuffer and be prepared to intervene early during the course of the patient's treatment.

Adult

Frequent users of the emergency department: can we intervene?

OBJECTIVE: To determine whether the use of individualized patient care plans and multidisciplinary case management would decrease ED utilization by frequent ED users. METHODS: The authors performed a prospective, randomized clinical trial of the impact of a care plan on ED use by adults with frequent ED visits. Patients with > 10 ED visits to a university hospital in 1993 were identified. Patients were matched for age, sex, and number of visits and then randomized into 2 groups. The control group received standard emergency care. The treatment group was managed by a multidisciplinary team and treated in the ED according to individualized care plans. ED use was tracked at the university hospital and at the other 5 community hospitals in the city. RESULTS: Of the 70 enrolled patients, 25 of 37 control patients and 27 of 33 treatment patients made visits to the university hospital during the 1-year study period. Only those patients with follow-up visits were included in the data analysis. Patients remaining in the control group made 247 total visits (range 1-65) to the university hospital and 179 total visits (range 0-38) to the community hospitals during the study period. Patients in the treatment group made 320 total visits (range 1-72) to the university hospital and 254 total visits (range 0-135) to the community hospitals during the study period. There was no significant difference in the median number of visits made to either the university hospital or the community hospitals by the patients in the control group and those in the treatment group. CONCLUSIONS: The use of individualized care plans and case management did not significantly decrease ED utilization by frequent ED users. However, the impact of individualized care plans and case management on other quality-of-care measures (e.g., patient satisfaction, ED length of stay, hospitalizations, primary care visits, and health care costs) remains to be determined.

Adult

Research subject enroller program: a key to successful emergency medicine research.

OBJECTIVE: To describe the successful use and impact of individuals paid to enroll clinical research subjects in support of emergency medicine (EM) research. PROGRAM DESCRIPTION: Paramedics and college students were hired to identify/enroll subjects in EM research studies 14 hours/day, 7 days/week. Potential subjects were identified by monitoring emergency medical services radios, routine rounding in the ED, and communication with the ED attending and charge nurse. Enrollers were trained in phlebotomy, obtaining ECGs, obtaining consent in appropriate studies, and post-ED follow-up. They supported ED prospective studies and multicenter clinical trials, as well as departmental surveys and retrospective studies. Survey support included mailing list development, mailing completion, survey database design, and data entry. PROGRAM OUTCOMES: Over 18 months, 17 prospective studies and 8 surveys/retrospective studies were completed. 2,175 subjects were enrolled in prospective studies and 6,500 surveys/retrospective reviews were completed. In the year prior to enroller program initiation, < 100 subjects were enrolled in 3 departmental studies. CONCLUSION: Use of paid, clinical research subject enrollers supports successful recruitment of study subjects and the completion of EM research studies.

Academic Medical Centers

Do admitted patients held in the emergency department impact the throughput of treat-and-release patients?

OBJECTIVE: To examine the impact of reducing ED "boarders" (through the use of a short-stay inpatient medicine unit) on the amount of time that treat-and-release patients spend in the ED. METHODS: A retrospective analysis of hours spent in the ED was made at a university hospital teaching ED for treat-and-release patients in 4 clinical categories: chest pain, asthma exacerbation, sickle-cell crisis, and seizure. The average hours per patient spent in the ED during the 4-month intervals before (August-November 1993) and after (August-November 1994) the establishment of the short-stay medicine unit were compared. Data were analyzed using the 2-tailed, unpaired t-test. RESULTS: This short-stay inpatient medicine unit received on average 135 patients per month from the ED, with an average length of stay of 2.4 days. The mean (+/-SD) number of admitted patients per day waiting in the ED > 8 hours for an inpatient bed dropped from 9.6 +/- 4.2., before the institution of this unit, to 2.3 +/- 2.6. There was a significant reduction in the average number of hours spent in the ED by treat-and-release patients with chest pain (from 7.3 +/- 6.0 to 5.5 +/- 4.8 hr/patient, p < 0.001) and asthma exacerbation (from 5.0 +/- 3.6 to 4.2 +/- 2.9 hr/patient, p < 0.05), but not with sickle-cell crisis or seizure, after the implementation of the short-stay unit. CONCLUSION: Reducing the number of admitted patients waiting in the ED for inpatients beds, in this case by establishment of a short-stay medicine unit, is associated with a decrease in the interval that treat-and-release patients spend in the ED.

Adult

Use of sodium polystyrene sulfonate in a lithium overdose.

A 23-year-old woman with an acute-on-chronic lithium overdose received multiple oral doses of sodium polystyrene sulfonate totaling 150 g over a 24-hour period. During the 33 hours after the institution of therapy, the serum lithium level decreased from 4.20 to 0.68 mEq/L. The calculated serum lithium elimination half-life of 12 hours is significantly shorter than that previously noted in other similar overdoses, and the patient suffered no adverse effects of therapy. Multiple-dose sodium polystyrene sulfonate may be useful in lowering the serum lithium level of select patients with acute lithium overdoses but is not a substitute for hemodialysis in severely ill patients.

Acute Disease

Enhanced activated charcoal delivery through small-bore tubing.

Activated charcoal is often given through small-bore tubing for pediatric patients or in attempts to bypass the stomach in patients who are vomiting. The viscosity makes activated charcoal difficult to administer through small-bore tubing. This in vitro study examined several interventions to facilitate flow of aqueous suspension activated charcoal through the small-bore tubing. Aqueous suspension activated charcoal with or without sorbitol had similar flow rates. Precoating the tubing with mineral oil gave only minimal increases in flow rate. A 10% dilution decreased the time to administer 240 ccs of aqueous suspension activated charcoal by 2/3. An additional 10% dilution reduced the time to administer the same dose a further 50%. Minimal dilution of aqueous suspension activated charcoal with tap water greatly increased flow rate through small-bore tubes.

Charcoal

Failure of N-acetylcysteine to reduce alpha amanitin toxicity.

Acetaminophen undergoes toxic conversion in the liver to a free-radical intermediary which binds to glutathione. N-Acetylcysteine acts as a glutathione precursor when natural stores are depleted, and is an effective antidote for acetaminophen overdose. Mushrooms containing amatoxins (such as Amanita phalloides) may undergo similar toxic conversion. However, in our amatoxin-poisoned mouse model, N-acetylcysteine (1.2 g kg-1) produced no change in survival or hepatic enzyme elevation compared to control animals. We conclude that N-acetylcysteine has no clinical role in the treatment of Amanita phalloides ingestion.

Acetylcysteine

Common electrolyte imbalances associated with malignancy.

More than one million Americans will be diagnosed with cancer during 1992, and 50% will be cured of their disease. Of those individuals not cured of the malignancy, survival time after diagnosis has increased tremendously compared to 1980. Because of advances in therapy and the increase in long-term survival, the presence of cancer patients in critical care units should no longer represent either a medical contradiction or an ethical dilemma when the condition requiring critical care is potentially reversible. Many of these individuals may become patients in critical care settings as a result of specific electrolyte imbalances caused by the malignant disease or treatment of malignancy. Although the imbalances often are temporary, they can be life-threatening without intervention. The most common temporary electrolyte imbalances associated with malignant conditions are hypercalcemia, hyperkalemia, and tumor lysis syndrome. Critical care nurses can contribute skill and knowledge in ameliorating these conditions so that the person with cancer can have better quality and longer survival time.

Adult

Orthotopic liver transplants necessitated by acetaminophen-induced hepatotoxicity.

BACKGROUND: Acetaminophen-induced hepatotoxicity has been recognized since 1966. Patients experiencing a massive hepatic insult due to acetaminophen (APAP) may recover with minimal residual complications or develop fulminant hepatic necrosis. We report 3 patients with hepatic failure due to an APAP overdose who received orthotopic liver transplants and survived. CASE REPORTS: An 18-y-o female ingested 60 500 mg APAP tablets (30 g). She presented with tachycardia and lethargy stating that she had taken amoxipine, carbamazepine, and lorazepam. She began to recover but on day 2 experienced an upper gastrointestinal bleed and became hypotensive and hyperpyrexic. She developed hepatic encephalopathy and it was then determined she had ingested APAP. Her APAP level was 13 micrograms/ml 96 h post-ingestion. She was successfully transplanted 19 d post-ingestion with recovery. A 40-y-o female was admitted for flu-like symptoms persisting for 7 d. She was jaundiced, hyperventilating and hypotensive. She admitted ingesting approximately 17 g APAP over 36 h. Her APAP level was 12.2 micrograms/ml. Her condition worsened and on day 3 she was in grade IV coma. She was successfully transplanted 4 d post-arrival with recovery. A 16-y-o female ingested an unknown amount of APAP. She presented approximately 24 h post-ingestion with a serum APAP level of 130 micrograms/ml. Her condition deteriorated and she became encephalopathic with grade IV coma. She was successfully transplanted on day 7 post-arrival. DISCUSSION: Hepatotoxicity can occur as a result of either acute or chronic APAP overdose. Although n-acetylcysteine (NAC) is effective antidotal therapy, it must be used within 8-12 h post-ingestion to be optimally effective. Inaccurate patient histories may prevent NAC administration resulting in hepatotoxicity. CONCLUSION: Liver transplantation is a viable option to be considered in those APAP overdose patients who experience rapidly progressing encephalopathy, hemolysis, and hepato-renal failure.

Acetaminophen

Using diversional activity to enhance coping.

Diversional activity deficit, a nursing diagnosis that occurs with prolonged hospital treatment, requires creative and practical ways for nurses to support patients. A tool designed to assess diversional needs is described. Benefits include improved relationships and enhanced patient coping with a minimum of cost and inconvenience.

Adaptation, Psychological

Effects of alternate routes of epinephrine delivery in experimental bradycardia-hypotension.

The magnitude and rapidity of response to epinephrine given by various routes were evaluated using a new model of bradycardia and hypotension. In ten animals, left ventricular (LV) injection of 10 micrograms/kg of epinephrine was superior to right ventricular (RV) injection in regard to time to attain a 20% increase in heart rate (HR), a 10% increase in mean arterial pressure (MAP) and time to reach peak MAP, although the peak MAP itself did not significantly differ. Similar results occurred with a 15 micrograms/kg dose. Aortic injection in seven of the animals resulted in a much longer time to target HR, an equal time to target MAP and a longer time to peak MAP compared to LV injection. LV injection of epinephrine results in a significantly more rapid onset of action than RV injection in the bradycardic, hypotensive animal. Epinephrine's beneficial effect appears to be derived from its vasoconstrictive, chronotropic and inotropic properties.

Animals