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Biomedical subjects

S A Bernard

Publications and source records attributed to S A Bernard.

At least 19 recordsLinked to original sources

High tissue affinity angiotensin-converting enzyme inhibitors improve endothelial function and reduce infarct size.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors differ in their ability to inhibit tissue ACE. This study was, therefore, undertaken to determine whether high tissue affinity ACE inhibitors would improve endothelial function and thereby decrease tissue necrosis during ischemia. METHODS: In a porcine model, the second and third diagonal vessels were occluded for 90 minutes, followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion. During the period of coronary occlusion, 10 pigs received enalaprilat (low affinity tissue ACE inhibitor), 0.05 mg/kg intravenously, 10 received quinaprilat (high affinity tissue ACE inhibitor), 10 mg intravenously, and 10 others received no ACE inhibitor. RESULTS: Wall motion scores (4, normal, to -1, dyskinesia) were higher in animals treated with ACE inhibitors (3.20+/-0.15 SE enalaprilat versus 3.08+/-0.23 quinaprilat versus 1.52+/-0.07 no ACE; both p < 0.0001 from no ACE). Endothelial-dependent relaxation to bradykinin was best preserved in the quinaprilat-treated hearts (32.1%+/-7.6% enalaprilat versus 65.8%+/-12.6% quinaprilat versus 30.6%+/-10.7% no ACE; p < 0.0001 from no ACE; p < 0.005 from enalaprilat). This was associated with a greater reduction in infarct size: area necrosis/area risk 24.3%+/-0.8% enalaprilat (p < 0.0001 from no ACE) versus 14.3%+/-3.2% quinaprilat (p < 0.0001 from no ACE; p < 0.005 from enalaprilat) versus 40.0%+/-1.7% no ACE. CONCLUSIONS: ACE inhibitors with higher affinity to tissue ACE result in better preservation of endothelial function and less tissue necrosis during coronary revascularization.

Angiotensin-Converting Enzyme Inhibitors↗

Primary tumors of the spine.

Primary osseous tumors of the spine are rare lesions and much less frequently encountered than metastases, multiple myeloma, and lymphoma. The interpreting radiologist must be aware of the typical radiographic appearance of the most common nonmyeloproliferative tumors of the spine because these tumors must be considered when a solitary spinal lesion is encountered. The purpose of this article is to describe the radiologic appearance and radiologic staging of the most common benign (hemangioma, enostosis, osteoid osteoma, osteoblastoma, giant cell tumor, aneurysmal bone cyst, and osteochondroma) and malignant (chordoma, chondrosarcoma, Ewing tumor, and osteosarcoma) osseous spine tumors.

Diagnosis, Differential↗

Drug interactions in palliative care.

PURPOSE: This review of drug interactions in palliative care examines the relevant literature in this area and summarizes the information on interactions of drugs, nutrients, and natural products that are used in the palliative care setting. Particular emphasis is placed on describing the newer information on the cytochrome P450 (CYP) system and the interactions of opioids, antidepressants, and the antitussive, dextromethorphan. METHODS: We performed a search of the MEDLINE database of the time period from 1966 until April 1998, using medical subject headings such as the names of selective serotonin reuptake inhibitors and other relevant medications in palliative care. Literature reviewed included both human and animal articles as well as non-English literature. Bibliographies of these articles and the personal libraries of several palliative care specialists were reviewed. Software developed by The Medical Letter-The Drug Interaction Program was also used. RESULTS: Drug interactions can be categorized in several ways. Drug-drug interactions are the most well known and can be kinetic, dynamic, or pharmaceutical. Pharmacokinetic interactions can involve CYP 2D6, which acts on drugs such as codeine and is responsible for its conversion to morphine. Poor metabolizers, either genotypic or due to phenocopying, are at risk for undertreatment if not recognized. Pharmacodynamic interactions with dextromethorphan may produce serotonin syndrome. CONCLUSION: Drug interactions are important in palliative care as in other aspects of medicine. These interactions are similar to those seen in other areas of medical care but have significant consequences in pain management. Failure to recognize these interactions can lead to either overdosing or undertreatment.

Drug Interactions↗

Recognising clinical instability in hospital patients before cardiac arrest or unplanned admission to intensive care. A pilot study in a tertiary-care hospital.

OBJECTIVE: To investigate the nature and duration of clinical instability (i.e., abnormalities in simple physical observations or laboratory test results) in hospital patients before a "critical event" (i.e., a cardiac arrest or an unplanned admission to intensive care). DESIGN: Retrospective survey of medical records of all patients having critical events (CEs) over 12 months. Data on hospital and Intensive Care Unit (ICU) patients were obtained for comparison with the study population. SETTING: A 300-bed metropolitan teaching hospital with a seven-bed ICU. PATIENTS: All patients having CEs over a 12-month period (January to December 1997). MAIN OUTCOME MEASURES: Number of patients with clinical instability before a CE; duration of clinical instability before a CE; number of medical reviews of each patient before a CE; mortality rate and length of hospital stay for all patients. RESULTS: There were 122 CEs in 112 patients (median, 1; range, 1-4). Of the CEs, 79 were unplanned ICU admissions (14 subsequent to cardiac arrest calls), and 43 were cardiac arrest calls not resulting in ICU admission. Each CE was preceded by a median of two (range, 0-9) criteria for clinical instability. The median duration of instability before a CE was 6.5 hours (range, 0-432 hours), and in that time a median of two (range, 0-13) medical reviews took place. The incidence of CEs in the total hospital population (122 CEs/19,853 admissions) and in ICU patients (79 unplanned admissions/515 admissions) was 0.6% and 15%, respectively. There were 70 deaths (62%) among the 112 patients, compared with a total of 392 deaths (2% of admissions) in the hospital, of which 107 were in ICU. CONCLUSIONS: Very few patients suffer a CE while in hospital. However, those who do frequently manifest abnormalities in simple physical observations and laboratory test results before the CE. More rapid intervention in response to warning signs might provide a better outcome for these patients.

Adult↗

Pilot study of local autologous tumor infiltrating lymphocytes for the treatment of recurrent malignant gliomas.

A prospective pilot study was performed in order to assess the safety of treating recurrent malignant gliomas (MGs) with locally infused autologous tumor infiltrating lymphocytes (TILs) and recombinant interleukin-2 (rIL-2). Six patients were entered between June 27, 1994 and June 2, 1995 and followed until July 1, 1998. At surgery an Ommaya reservoir was placed for later infusion of TILs and rIL-2. Following surgery, autologous TILs were expanded in vitro in the presence of rIL-2 and infused on treatment days 1 and 14, with concurrent rIL-2 infusions performed three times each week for one month. Following completion of immunotherapy all patients were offered chemotherapy. Phenotypic analysis demonstrated TILs to be T-lymphocytes (87-99% CD3+). Of these, 4 of 6 cases (67%) phenotyped as cytotoxic/suppressor T-lymphocytes (CD8+) and 2 of 6 cases (33%) phenotyped as helper/inducer T-lymphocytes (CD4+). TILs demonstrated limited selective cytotoxicity, with dose dependent cytotoxicity against autologous tumor, allogenic tumor and long term MG cell lines. There were no significant (Grade 3 or 4) complications. One patient developed transient low grade fevers, and 2 developed asymptomatic hydrocephalus. All patients developed transient and asymptomatic cerebral swelling, noted on the immediate post-treatment imaging studies. At three and six month follow-up, 3 patients responded with partial response, 2 demonstrated stable disease and 1 patient progressed. At long term follow-up, 1 patient had a complete response (45 month follow-up), 2 had a partial response (48 and 47 month follow-up) and 3 patients expired as a result of progressive disease (at 12, 12 and 18 months following immunotherapy). A relationship between subsequent chemotherapy or extent of resection to outcome was not apparent but could not be excluded. This pilot study demonstrated that locally infused autologous TILs and rIL-2 could be delivered without serious toxicity. Further studies are indicated to determine the safety and long term efficacy of TIL immunotherapy.

Adult↗

The evaluation of cocaine-induced chest pain with acute myocardial perfusion imaging.

OBJECTIVE: To use myocardial perfusion imaging to determine the etiology of cocaine-induced chest pain in patients without ECG evidence of acute cardiac ischemia. METHODS: The authors conducted a prospective study of consecutive consenting patients aged 18-70 years with cocaine-induced chest pain who reported cocaine use within three days and presented with a chief complaint of chest pain occurring within three hours and lasting longer than 15 minutes with a normal or nondiagnostic ECG. Patients were excluded if they had a clear-cut noncardiac cause of chest pain, ECG evidence of acute cardiac ischemia, history of myocardial infarction, pregnancy, or lactation, required immediate hospitalization, or were unable to consent. Patients were injected with Tc-99m tetrofosmin and imaged. Perfusion scans were independently read by two nuclear radiologists. Clinicians blinded to scan results determined patient disposition. Patients with abnormal scans were asked to return for follow-up resting scans. RESULTS: Fourteen patients were enrolled. Twelve of the 14 patients had chest pain at the time of Tc-99m tetrofosmin injection. Ten of the 14 [(71%) 95% CI = 48% to 95%] scans were normal or within normal limits. Four of the 14 [(29%) 95% CI = 5% to 52%] were abnormal. Of the four patients with abnormal scans, two had follow-up scans that demonstrated an irreversible perfusion abnormality, and two who did not return for follow-up reported no subsequent hospitalizations for acute cardiac ischemia. CONCLUSION: Perfusion imaging did not demonstrate reversible ischemia in most patients (12/14, 86%) with cocaine-induced chest pain without ECG evidence of ischemia. These results suggest that cocaine-induced chest pain in most patients without ECG evidence of ischemia is not due to acute ischemia.

Adolescent↗

Phase I trial of twice-weekly gemcitabine and concurrent radiation in patients with advanced pancreatic cancer.

PURPOSE: To determine the maximum-tolerated dose, dose-limiting toxicities, and potential antitumor activity of twice-weekly gemcitabine and concurrent radiation in patients with locally advanced pancreatic cancer. PATIENTS AND METHODS: Nineteen patients with histologically confirmed adenocarcinoma of the pancreas were studied at the Wake Forest University Baptist Medical Center and the University of North Carolina at Chapel Hill. The initial dose of gemcitabine was 20 mg/m(2) by 30-minute intravenous infusion each Monday and Thursday for 5 weeks concurrent with 50.4 Gy of radiation to the pancreas. Gemcitabine doses were escalated in 20-mg/m(2) increments in successive cohorts of three to six additional patients until dose-limiting toxicity was observed. RESULTS: The dose-limiting toxicities at 60 mg/m(2) given twice-weekly were nausea/vomiting, neutropenia, and thrombocytopenia. Twice-weekly gemcitabine at a 40-mg/m(2) dose was well tolerated. Of the eight patients eligible for a minimum follow-up of 12 months, three remain alive, one of whom has no evidence of disease progression. CONCLUSION: A dose of twice-weekly gemcitabine at 40 mg/m(2) produced mild thrombocytopenia, neutropenia, nausea, and vomiting when delivered with concurrent radiation to the upper abdomen in patients with advanced pancreatic cancer. These data suggest this regimen is well tolerated and may possess significant activity. These data and other observations have resulted in a phase II Cancer and Leukemia Group B study to ascertain the efficacy of this treatment regimen in patients with locally advanced pancreatic cancer.

Adult↗

Use of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) to assist with triage of patients with chest pain or other symptoms suggestive of acute cardiac ischemia. A multicenter, controlled clinical trial.

BACKGROUND: Approximately 6 million U.S. patients present to emergency departments annually with symptoms suggesting acute cardiac ischemia. Triage decisions for these patients are important but remain difficult. OBJECTIVE: To test whether computerized prediction of the probability of acute ischemia, used with electrocardiography, improves the accuracy of triage decisions. DESIGN: Controlled clinical trial. SETTING: 10 hospital emergency departments in the midwestern, southeastern, and northeastern United States. PATIENTS: 10689 patients with chest pain or other symptoms suggestive of acute cardiac ischemia. INTERVENTION: The probability of acute ischemia predicted by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI), either automatically printed or not printed on patients' electrocardiograms. MEASUREMENTS: Emergency department triage to a coronary care unit (CCU), telemetry unit, ward, or home. Other measurements were the bed capacity of the CCU relative to that of the telemetry unit; training or supervision status of the triaging physician; and patient diagnoses and outcomes based on clinical, electrocardiographic, and creatine kinase data. RESULTS: For patients without cardiac ischemia, in hospitals with high-capacity CCUs and relatively low-capacity cardiac telemetry units, use of ACI-TIPI was associated with a reduction in CCU admissions from 15% to 12%, a change of -16% (95% CI, -30% to 0%), and an increase in emergency department discharges to home from 49% to 52%, a change of 6% (CI, 0% to 14%; overall P=0.09). Across all hospitals, for patients evaluated by unsupervised residents, use of ACI-TIPI was associated with a reduction in CCU admissions from 14% to 10%, a change of -32% (CI, -55% to 3%); a reduction in telemetry unit admissions from 39% to 31%, a change of -20% (CI, -34% to -2%); and an increase in discharges to home from 45% to 56%, a change of 25% (CI, 8% to 45%; overall P=0.008). Among patients with stable angina, in hospitals with high-capacity CCUs, use of ACI-TIPI was associated with a reduction in CCU admissions from 26% to 13%, a change of -50% (CI, -70% to -17%), and an increase in discharges to home from 20% to 22%, a change of 10% (CI, -29% to 71%; overall P=0.02). At hospitals with high-capacity telemetry units, use of ACI-TIPI was associated with a reduction in telemetry unit admissions from 68% to 59%, a change of -14% (CI, -27% to 1%), and an increase in emergency department discharges to home from 10% to 21%, a change of 100% (CI, 22% to 230%; overall P=0.02). Among patients with acute myocardial infarction or unstable angina, use of ACI-TIPI did not change appropriate admission (96%) to the CCU or telemetry unit at hospitals with high-capacity CCUs or telemetry units. CONCLUSIONS: Use of ACI-TIPI was associated with reduced hospitalization among emergency department patients without acute cardiac ischemia. This result varied as expected according to the CCU and cardiac telemetry unit capacities and physician supervision at individual hospitals. Appropriate admission for unstable angina or acute infarction was not affected. If ACI-TIPI is used widely in the United States, its potential incremental impact may be more than 200000 fewer unnecessary hospitalizations and more than 100000 fewer unnecessary CCU admissions.

Acute Disease↗

Soluble complement receptor type I limits damage during revascularization of ischemic myocardium.

BACKGROUND: This study was undertaken to determine whether suppression of complement activation with soluble human complement receptor type I reduces myocardial damage during the revascularization of ischemic myocardium. METHODS: In 20 pigs, the second and third diagonal coronary arteries were occluded for 90 minutes, followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion. In 10 pigs, soluble human complement receptor type I (10 mg/kg) was infused over 30 minutes before the period of coronary occlusion; 10 other pigs received no soluble human complement receptor type I. Complement activation was measured by total hemolytic complement activity (expressed as a percentage of preischemic values). Ischemic damage was assessed by changes in myocardial tissue pH, wall motion scores (range, 4=normal to -1=dyskinesia), and infarct size (area of necrosis versus area at risk). RESULTS: After 180 minutes of reperfusion, hearts treated with soluble human complement receptor type I had significantly less complement activation than nontreated hearts (1.1%+/-0.09% versus 7.8%+/-0.04%, respectively; p < 0.002), less myocardial acidosis (-0.41+/-0.03 versus -0.72+/-0.03, respectively; p < 0.0001), higher wall motion scores (3.1+/-0.09 versus 1.67+/-0.16, respectively; p < 0.0001), and smaller infarct size (24.6%+/-2.0% versus 41%+/-1.3%, respectively; p < 0.0001). CONCLUSIONS: Complement inhibition with soluble human complement receptor type I significantly limits ischemic damage during the revascularization of acutely ischemic myocardium.

Acidosis↗

Cancer pain survey: patient-centered issues in control.

It is widely believed that patients' reluctance to report pain and adhere to treatment recommendations are significant barriers to cancer pain control. However, few investigators have examined barriers to cancer pain management from the cancer patient's perspective. Ambulatory patients with cancer who had experienced cancer-related pain in the previous month or were currently taking analgesics for cancer pain control were asked to participate in this study. Information regarding (a) pain assessment, (b) pain medication use, (c) concerns and barriers to compliance, (d) communication patterns regarding pain and pain control, and (e) demographics were collected during a 10-min structured interview. Approximately 20% of patients with a current cancer diagnosis who were approached reported that they had experienced pain or taken analgesic drugs during the preceding month. Eighty-eight percent of these patients ranked their pain as five or greater (scale, 0-10), and 81% reported impaired function due to pain. Major barriers to effective treatment included forgetfulness, the belief that pain should be tolerated, concerns about side effects, and fear and disdain of dependence, addiction, and tolerance. One-third of patients felt that their pain could not be better controlled than it currently was. Patients reported frequent communication regarding pain and pain control with physicians (52%), nurses (41%), and pharmacists (17%). The low pain prevalence, coupled with high pain intensity and associated dysfunction, appears to be a reflection of patient's unwillingness to report pain of mild to moderate intensity. In addition to previously recognized factors, stoicism and fatalism represent significant barriers to cancer pain control.

Adult↗

Pain management issues: the cost of medications in rural settings.

Cost of analgesic and adjuvant medications used by rural patients with cancer cared for by 29 nurses participating in an in-depth education program were evaluated before and after the program. Across all time periods, the median daily cost was $5.16 across all medications. Average daily cost and maximum and median cost of all medications were $5.36, $74.38 and $3.58, respectively. Average daily cost did not change over time. Average pain intensity did not change over time and was not related to prescribing patterns or daily costs. While professional education was demonstrated to produce change in prescribing practices, further research is needed to evaluate patterns of medication administration and effectiveness patterns using reliable outcome measures other than self report of pain intensity.

Adult↗

Heparin-bonded circuits decrease myocardial ischemic damage: an experimental study.

BACKGROUND: Heparin-bonded cardiopulmonary bypass circuits reduce complement activation, but their effect on myocardial function is unknown. This study was undertaken to determine whether heparin-bonded circuits reduce myocardial damage during acute surgical revascularization. METHODS: In 16 pigs, the second and third diagonal vessels were occluded with snares for 90 minutes followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion with the snares released. During the period of coronary occlusion, all animals were placed on percutaneous bypass followed by standard cardiopulmonary bypass during the periods of cardioplegic arrest and reperfusion. In 8 pigs, heparin-bonded circuits were used, whereas 8 other pigs received nonbonded circuits. RESULTS: Animals treated with heparin-bonded circuits had the best preservation of wall motion scores (3.5 +/- 0.3 versus 2.3 +/- 0.2; 4 = normal to -1 = dyskinesis; p < 0.05), least tissue acidosis (change in pH = -0.31 +/- 0.02 versus -0.64 +/- 0.08; p < 0.05), smallest increase in lung H2O (1.7% +/- 0.7% versus 6.1% +/- .5%; p < 0.05), and the lowest area of necrosis/area of risk (20.3% +/- 2.2% versus 40.4% +/- 1.6%; p < 0.05). CONCLUSIONS: We conclude that heparin-bonded circuits significantly decrease myocardial ischemic damage during acute surgical revascularization.

Acid-Base Equilibrium↗

Induction chemoradiotherapy followed by esophagectomy in patients with carcinoma of the esophagus.

BACKGROUND: Induction chemoradiotherapy followed by esophagectomy may provide results superior to those of single-modality treatment in patients with esophageal cancer. The purpose of this study was to review our experience with this approach for esophageal cancer. METHODS: From 1988 to 1996, 166 consecutive patients with esophageal cancer were evaluated; 66 entered a protocol of chemotherapy (5-fluorouracil, cisplatin) concurrent with radiation (45 Gy) followed by esophagectomy. Fifty-four patients completed the protocol. RESULTS: Toxicity associated with induction chemoradiotherapy was minimal. The actuarial survival at 12, 24, and 36 months was 59%, 42%, and 32%, respectively. The pathologic complete response (pCR) rate was 41%, with 12-, 24-, and 36-month survivals of 77%, 50%, and 45%, whereas non-pCR patients had survivals of 46%, 35%, and 23%. The difference in survival between pCR and non-pCR patients was not significant (p = 0.13), but the difference in recurrence-free survival was significant (p = 0.007). CONCLUSIONS: This well-tolerated protocol resulted in a high pCR. Trimodality treatment for esophageal cancer may provide long-term survival in some patients regardless of their pCR status.

Adenocarcinoma↗

Clinical trial of induced hypothermia in comatose survivors of out-of-hospital cardiac arrest.

STUDY OBJECTIVE: To examine the effects of moderate hypothermia (33 degrees C), induced by surface cooling in the ED and maintained for 12 hours in the ICU, on patients with anoxic brain injury after out-of-hospital cardiac arrest. METHODS: We conducted the study in a teaching hospital in Melbourne, Victoria, Australia. Participants were 22 adults who remained unconscious after return of spontaneous circulation following out-of-hospital cardiac arrest. This treatment group was studied prospectively, and a control group of 22 similar patients was studied by retrospective chart review. Moderate hypothermia (33 degrees C) was induced in the ED by means of surface cooling and maintained for 12 hours in the ICU with rewarming to normothermia over 6 hours; control patients were maintained at normothermia. RESULTS: There were no significant adverse effects of induced hypothermia. Cardiovascular changes included decreased pulse rate, but there were no significant differences in mean arterial blood pressure between the two groups. Small increases in serum potassium and decreases in pH at 18 hours in the hypothermic patients compared with normothermic controls were of no clinical significance. There were no septic complications. There was a significant increase in the number of patients with good outcome (Glasgow Outcome Coma Scale category 1 or 2) with induced hypothermia (11 of 22, versus 3 of 22 for normothermic controls; P<.05), and the mortality rate was significantly lower (10 of 22 versus 17 of 22; P<.05). CONCLUSION: Compared with historical normothermic controls, outcome was significantly improved and there was no increase in complications when moderate hypothermia was induced in comatose survivors of out-of-hospital cardiac arrest and maintained for 12 hours. Larger, prospective, randomized, controlled studies of induced moderate hypothermia in comatose survivors of out-of-hospital cardiac arrest are warranted.

Aged↗

Concurrent radiation therapy and chemotherapy followed by esophagectomy for localized esophageal carcinoma.

PURPOSE: A prospective study was performed to determine the outcome of patients with esophageal cancer who received preoperative radiation therapy and chemotherapy followed by esophagectomy, and to determine the role of preresection esophagogastroduodenoscopy (EGD) in predicting the patients in whom surgery could possibly be omitted, and the impact of surgery on survival. MATERIALS AND METHODS: Thirty-five patients with localized carcinoma of the esophagus received concurrent external-beam radiotherapy and chemotherapy followed by esophagectomy. Patients received 45 Gy in 25 fractions. Chemotherapy consisted of continuous infusion fluorouracil (5-FU; 1,000 mg/m2/d) on days 1 through 4 and 29 through 32 and cisplatin (100 mg/m2) on day 1. Patients underwent an Ivor-Lewis esophagectomy 18 to 33 days after completion of radiotherapy. RESULTS: Eighty percent of the patients had squamous cell carcinoma and 20% had adenocarcinoma. In addition, 51% had a pathologic complete response (CR). Twenty-two of the 35 underwent a preresection EGD before resection. Seventeen of the 22 (77%) had negative pathology from the preresection EGD, but seven of the 17 (41%) had residual tumor at surgery. The median survival and disease-free survival rates for all patients were 25.8 months and 32.8 months, respectively. Eighteen patients (51%) had no tumor at resection. The median survival for these patients was 36.8 months; the median disease-free survival time has not been reached. The median survival and disease-free survival rate for the patients with residual tumor in the surgical specimen were 12.9 months and 10.8 months, respectively. CONCLUSION: Preresection EGD is not reliable for determining the presence of residual disease or the patients in whom surgery could be omitted. Twenty-five percent of the patients with residual tumor in the resected surgical specimen were long-term survivors; this suggests a benefit from esophagectomy after concurrent radiotherapy and chemotherapy.

Adenocarcinoma↗

Acute, reversible left ventricular dysfunction in status asthmaticus.

Three cases of rapidly reversible severe myocardial depression are described in patients with status asthmaticus. Initial echocardiograms obtained within 1 day of hospital admission revealed global left ventricular hypokinesis with ejection fractions of 11 to 34%. Follow-up echocardiograms obtained only 3 to 8 days later revealed marked improvement of left ventricular function. Possible mechanisms responsible for the observed rapidly reversible myocardial depression and the clinical implications of this finding are discussed.

Adult↗