Comparison of information processing technologies.

OBJECTIVE: To examine the type of information obtainable from scientific papers, using three different methods for the extraction, organization, and preparation of literature reviews. DESIGN: A set of three review papers was identified, and the ideas represented by the authors of those papers were extracted. The 161 articles referenced in those three reviews were then analyzed using 1) a formalized data extraction approach, which uses a protocol-driven manual process to extract the variables, values, and statistical significance of the stated relationships; and 2) a computerized approach known as "Idea Analysis," which uses the abstracts of the original articles and processes them through a computer software program that reads the abstracts and organizes the ideas presented by the authors. The results were then compared. The literature focused on the human papillomavirus and its relationship to cervical cancer. RESULTS: Idea Analysis was able to identify 68.9 percent of the ideas considered by the authors of the three review papers to be of importance in describing the association between human papillomavirus and cervical cancer. The formalized data extraction identified 27 percent of the authors' ideas. The combination of the two approaches identified 74.3 percent of the ideas considered important in the relationship between human papillomavirus and cervical cancer, as reported by the authors of the three review articles. CONCLUSION: This research demonstrated that both a technically derived and a computer derived collection, categorization, and summarization of original articles and abstracts could provide a reliable, valid, and reproducible source of ideas duplicating, to a major degree, the ideas presented by subject specialists in review articles. As such, these tools may be useful to experts preparing literature reviews by eliminating many of the clerical-mechanical features associated with present-day scientific text processing.

Tylenol Extended Relief overdose.

In this report we describe the toxicokinetics of the Tylenol Extended Relief (TER) preparation of acetaminophen in human overdose. We collected 41 cases of TER overdose from five regional poison centers. Patients who met the following criteria were studied: a single ingestion of TER alone; confirmed time of ingestion; at least four acetaminophen determinations; and normal concentrations of liver function enzymes. With the exception of standard decontamination measures, treatment with N-acetylcysteine (NAC) if any acetaminophen level was above the treatment line of the Rumack-Matthew nomogram, and additional acetaminophen determinations, no interventions were recommended. Our study group comprised 13 patients, 12 female and 1 male, with single overdoses of 10.4 to 65 g TER. The acetaminophen elimination half-life was 3.1 +/- .8 hours (mean +/- SD; range, 1.3 to 4.0 hours; n = 12). The elimination phase for patients 2, 3, 4, 6, 8, 9, 11, 13 was delayed until 8.0 +/- 2.8 hours (range, 5 to 14 hours) after ingestion. Patients 3, 8, and 11--who had initial acetaminophen levels below the "possible toxicity" line of the Rumack-Matthew nomogram--later had acetaminophen levels above this line. No patient demonstrated a late or second acetaminophen peak. We conclude that the elimination half-life of TER acetaminophen is similar to that reported in overdose of immediate-release acetaminophen overdose. In a subgroup of patients, drug absorption continued beyond the 2 to 4 hours previously reported in immediate-release acetaminophen overdose. On the basis of our data, the use of a single 4-hour acetaminophen determination may lead to failure to recognize patients with potentially toxic TER ingestion. Until more toxicokinetic data are available, a reasonable approach would be to obtain at least one additional acetaminophen determination at least 4 to 6 hours after the first, if the first is obtained 4 to 8 hours after ingestion. NAC treatment should be initiated if either level is above the nomogram line but not if both levels fall below the nomogram line.

Placental transfer of N-acetylcysteine following human maternal acetaminophen toxicity.

OBJECTIVE: To determine whether the antidote for acetaminophen poisoning, N-acetylcysteine, administered to pregnant women with acetaminophen toxicity, crosses the placenta and can be measured in the newborn circulation following delivery. DESIGN: Over a 15-month period, four pregnant women with acetaminophen toxicity, who delivered their infants while receiving the antidote N-acetylcysteine, were studied. Maternal and cord blood from three viable infants, and cardiac blood sampled during an autopsy on the fourth, were analyzed for the presence of N-acetylcysteine using high-performance liquid chromatography. Maternal and cord blood aminotransferase activities, and autopsy findings on the nonviable infant were used to assess hepatic injury. RESULTS: N-Acetylcysteine was detected in the cord blood of three viable infants and in cardiac blood of a fourth, sampled at the time of autopsy. The mean N-acetylcysteine concentration in cord blood was 9.4 micrograms/mL (+/-1.3). This is well within the range associated with therapeutic doses of N-acetylcysteine typically administered to adults with acetaminophen poisoning. No adverse sequelae developed in the three viable infants. The fourth infant, delivered at 22 weeks gestational age died 3 h after birth. All mothers recovered and none of the four infants had evidence of acetaminophen-related toxicity. CONCLUSIONS: This is the first study documenting placental transfer of N-acetylcysteine in humans and provides impetus for research establishing a direct antidotal effect of N-acetylcysteine in the fetus.

The clinical spectrum of Jin Bu Huan toxicity.

Herbal medications and other nontraditional medical therapies are becoming increasingly popular in the United States. We describe three children and three adults in whom severe toxic effects developed after ingestion of a Chinese herbal medication, jin bu huan, which is sold as Jin Bu Huan Anodyne Tablets. Jin bu huan produced distinct clinical syndromes after acute ingestion in children and long-term use in adults. A single, acute ingestion in children rapidly produced life-threatening neurologic and cardiovascular manifestations, while long-term jin bu huan use in adults was associated with hepatitis. Jin bu huan contains levo-tetrahydropalmatine, a potent neuroactive substance. The constituents of jin bu huan are misidentified on the package, resulting in significant delay in identifying the plant alkaloid responsible for its toxicity. Although perceived as innocuous, jin bu huan may produce major health effects. The highly concentrated formulation, the lack of childproof packaging, and the product insert listing indications for the treatment of serious medical conditions may all contribute to the development of toxic reactions.

Large scale synthesis of recombinant human thyrotropin using methotrexate amplification: chromatographic, immunological, and biological characterization.

Studies of human TSH (hTSH) structure and function have been limited by difficulties in producing large quantities of recombinant hormone. We describe a system for the stable expression of high levels of recombinant human TSH (rec hTSH) using a mutant form of dihydrofolate reductase (dhfr) as an amplifiable dominant selectable marker. A vector expressing both the hTSH alpha-subunit and the mutant dhfr was cotransfected with a hTSH beta-subunit expression vector into dhfr-deficient cells. Amplification of the transfected sequences by methotrexate selection, followed by cell culture in a hollow fiber perfusion system, yielded rec hTSH production as high as 100,000 microU/ mL. Immunoradiometric assays using five different antibodies revealed no differences in the immunological activities of rec hTSH and pituitary hTSH. Bioactivity was measured in a novel TSH bioassay coupling the generation of cAMP by a transfected hTSH receptor to the cAMP-dependent regulation of a luciferase reporter gene. The ED50 for bovine TSH in this bioassay was 1.4 ng/mL (3.5 x 10(-11) mol/L). The ratio of the ED50 values for rec hTSH and pituitary hTSH was 1.0:1.1 (P = NS), indicating that the two TSHs were of equivalent potency. In conclusion, we have developed techniques for the high level production of rec hTSH that is immunologically and biologically equivalent to pituitary hTSH. The ability to produce large quantities of rec hTSH using standard laboratory techniques should facilitate future studies, such as the development of clinically useful TSH analogs.

Clinical ergotism with lingual ischemia induced by clarithromycin-ergotamine interaction.

The macrolide class of antibiotics, including erythromycin and troleandomycin, is associated with clinically significant adverse drug interactions. This results from macrolide inhibition of cytochrome P-450 metabolism of numerous xenobiotics, resulting in elevated serum drug levels and clinical intoxication. Animal studies, however, suggest that clarithromycin, the newest approved macrolide antibiotic, has has less potential for adverse drug reactions. We describe a patient who, on her fifth day of clarithromycin therapy, developed clinical ergotism (i.e., hypertension, lingual ischemia, and peripheral cyanosis) several hours after administration of her usual 2-mg dose of ergotamine tartrate. To our knowledge, this is the first report of clinical ergotism precipitated by clarithromycin-ergotamine interaction and suggests that, like other macrolide antibiotics, ergot preparations should be avoided in patients who are taking clarithromycin.

Tracing expert thinking in clinical trial design.

This paper describes a method for the analysis of the clinical trial design process used by experts. With this procedure, the scientific ideas and their sources can be identified and related to the clinical trial protocol actually prepared by the experts. An example is given using the work of the Intergroup Rhabdomyosarcoma Study Committee (IRS). That committee has been the primary contributor of information dealing with the treatment of rhabdomyosarcoma in children. The IRS-III protocol was used in this analysis of expert behavior because the protocol was adopted by the leading pediatric oncology clinical trial groups in North America and Europe. The analysis showed that the experts rely heavily, for much of the design, on ideas presented in numerical displays in published documents. Further, those aspects of the design which are innovative can be traced and better understood by applying the new procedure.

Quantitatively expressed ideas in lymphoma: text versus numerical displays.

Quantitatively expressed ideas are linkages of two or more characteristics presented by the author in tables or graphs. Such ideas also may be expressed as sentences in the text of the Results section. This study investigated the relative importance of quantitative ideas expressed in the two formats in the same article. A random sample of fifty articles from the lymphoma literature containing numerical relationship displays was selected and each article was carefully read in order to identify and extract the quantitative ideas expressed in the text. Only those ideas not presented in numerical displays were extracted. The final database consisted of records describing numerical relationships displayed in tables and/or graphs and records describing numerical relationships expressed only in the text of the Results section. In this way, the study could determine the added advantages of reading the Results sections, over and above the information provided by the displays of numerical relationships. The text ideas were more difficult to find and extract and were found to be less important when compared with ideas from numerical displays. This study further substantiated the method of extracting quantitatively expressed ideas from numerical displays for rapid technical processing of scientific documents.

Immediate detection of early high-risk patients with acute myocardial infarction using two-dimensional echocardiographic evaluation of left ventricular regional wall motion abnormalities.

Forty-three patients with acute myocardial infarction (AMI) were studied with serial two-dimensional echocardiography (2DE) to define a high-risk subset for in-hospital cardiovascular complications including pump failure, life-threatening arrhythmias, or death. A 2DE segment score was developed representing the extent of left ventricular (LV) regional wall motion abnormality (WMA) which was correlated with peak total creatine kinase (CK) release. Patients with transmural AMI had a segment score of 7.2 +/- 3.8, whereas those with nontransmural AMI had a segment score of 4.7 +/- 3.4 (p less than 0.025). Peak total serum CK enzyme level correlated statistically with segment score but with a low correlation coefficient. Thirteen (30%) of the 43 patients had an in-hospital complication and their segment score was 10.0 +/- 3.4 compared to 4.6 +/- 2.7 in those patients without a complication (p less than 0.005). A segment score greater than or equal to 8 was found in 11 of 13 (85%) of those who suffered a cardiac complication and in only five (16%) of the 30 patients without complication (p less than 0.05; sensitivity 85%, specificity 83%). Patient's initial clinical Killip classification was specific but very insensitive in predicting an early complicated course. Thus, 2DE study of LV regional wall motion can predict in the immediate post-AMI stage the in-hospital likelihood of such patients developing a cardiovascular complication during acute myocardial infarction.

Immediate diagnosis of acute myocardial infarction by two-dimensional echocardiography.

To define the role of portable two-dimensional echocardiography (2-D echo) in the immediate diagnosis of acute chest pain syndrome, 80 consecutive patients were studied. Adequate 2-D echo studies were obtained in 65 (81%). Thirty-three patients had clinical evidence of transmural or nontransmural acute myocardial infarction (AMI), 18 of whom had nondiagnostic initial ECGs. Thirty-two did not have a clinical AMI. Thirty-one of the 33 (94%) patients with clinical AMI had regional wall motion abnormalities on the initial 2-D echo; the other two had uncomplicated nontransmural AMIs, diagnosed only by ECG in one and by ECG and moderate elevation of CK-MB isoenzyme in the other. Twenty-seven of the 32 patients without clinical AMI had normal regional wall motion on the initial 2-D echo and none had a complication (severe arrhythmia, recurrent pain, heart failure or death) during the hospital course. Conversely, 10 of the 36 patients with initial 2-D echo regional wall motion abnormalities had a complication (p less than 0.05). Thus, in patients with acute chest pain syndrome, an initial 2-D echo that shows no regional wall motion abnormality suggests that such patients will not develop an AMI or clinical complication during the hospital course. An initial 2-D echo with regional wall motion abnormality identifies a high-risk group of patients who are likely to have AMI and important cardiac complications and may, therefore, benefit from admission to an intensive care unit.

Aortic dissection following coronary arterial bypass graft surgery.

A 60-year-old man underwent coronary arterial bypass graft surgery for unstable angina. After surgery, he developed a widened mediastinum on the chest x-ray film and a murmur consistent with aortic regurgitation. He refused study until the return of his anginal symptoms five years after surgery. At that time the patient had unchanged chest x-ray film and physical findings. Aortograms revealed a large type-1 aortic dissection extending from the aortic root to the descending thoracic aorta. Long-term survival with an aortic dissection after coronary arterial bypass grafting is possible. The pathophysiologic and pathologic findings of a spontaneous type-1 aortic dissection may differ from that of the dissection described herein, and these differences may relate to survival.