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Biomedical subjects

S Stern

Publications and source records attributed to S Stern.

At least 145 records · Page 8Linked to original sources

Systemic lupus erythematosus activity. An operational definition.

Improved diagnosis and treatment have reduced mortality from SLE and present us with an opportunity to consider SLE in finer distinctions than alive or dead. Although much has been learned about SLE without a gold standard of disease activity or a universally agreed-upon definition of SLE activity, standardization of one or more measures would greatly enhance our ability to compare results from different centers and to communicate more precisely. It is unlikely that any of the existing measures or any ones to be developed will completely satisfy everyone's needs but it is pointless to proliferate new ones without testing their metric properties. Some differences in concept are desirable, particularly for investigators who have specialized interests or insights, but each should meet criteria of reliability and validity and have explicit definitions of terms, rules for their ascertainment, and the time period covered. Moreover, agreement on minimum essential elements of any SLE activity measure and their operational definitions would be a boon. SLE activity is one dimension in the disease pathway of lupus and implies a continuous phenomena that is potentially reversible. Organ damage, another point in the path of causation, connotes irreversible disease. We recommend that minimum essential elements be based on their frequency of occurrence, biological sensibleness, and the likelihood that degrees of activity can be rated reliably to show a change in a clinical state. The rating should be independent of whether a therapy is employed. Since activity is always considered with severity, the two dimensions could be recognized in the scale. Severity can be used to expand a scale's gradations if a symptom or sign is present. Severity could be rated by the need to treat with immunosuppressive agents, the need to follow the patient more closely, or the functional or prognostic consequences of the manifestation. For every organ system clinical judgment should be used to decide whether and how the scale should be constructed. For instance, in skin manifestations one could construct a scale by describing the extent of the lesion over the body and whether the lesion has potential for scarring, i.e., involving the dermis. However, the presence of, rather than the number of, cytoid bodies might be the only thing that is clinically important in rating the eye.(ABSTRACT TRUNCATED AT 400 WORDS)

Diagnosis-Related Groups↗

Day-to-day variability of myocardial ischemic episodes in coronary artery disease.

Twenty patients with chronic stable angina pectoris, proved coronary artery disease, positive treadmill stress test response, and at least 2 episodes of ischemia per day underwent 72 hours of Holter monitoring during daily activities. During this period they had 389 ischemic episodes: 104 (27%) symptomatic and 285 (73%) silent. Marked variability was observed between patients in the number of ischemic episodes (range 2 to 15 per day, mean 6.5), duration of ischemia (range 6 to 419 minutes/day, mean 76.5), maximal ST depression (range 1 to 6 mm, mean 3.4) and heart rate at the beginning of ST depression (range 75 to 105 beat/min, mean 91). The day-to-day variability in individual patients between the different days in the number of ischemic episodes was 36%, in duration 51%, and in maximal degree of ST depression 31%. Only 9% variability was noted in heart rate at the beginning of ST depression. Similar day-to-day variability in individual patients was noted in the symptomatic and silent episodes. For clinical purposes of evaluation of ischemia during daily activities, 1 day of monitoring appears to be sufficient because within the first day, 78% of the maximal number of ischemic episodes, 64% of their duration, and 84% of the maximal degree of ST depression were detected. However, for evaluation of anti-ischemic drugs at least 2 monitoring days are required.

Aged↗

Cholestasis and liver failure with lambda-AL amyloidosis.

Clinically significant liver involvement in systemic amyloidosis, especially with cholestasis, is rare. We report a case of primary amyloidosis with severe intrahepatic cholestasis leading to terminal liver failure. The present case is the first of its kind reported involving Lambda light chains only as the associated paraprotein. Conventional treatment and a therapeutic trial with dimethyl sulphoxide were unsuccessful.

Aged↗

Silent myocardial ischemia: diagnosis, clinical significance and management.

With the inception of continuous ECG monitoring with high-fidelity reproduction of the ST-segment, silent myocardial ischemia has been regarded with increasing importance in the detection and management of coronary artery disease. With the aid of a variety of invasive and noninvasive methods, the validity of ST-segment depression as indicative of myocardial ischemia, even in the absence of symptoms, has been adequately documented. In completely asymptomatic subjects with positive evidence of silent ischemia in the exercise ECG or Holter monitoring, the risk of developing a future manifestation of coronary artery disease may be up to ten-fold higher than in individuals with negative tests In patients with established coronary artery disease, concomitant use of continuous ECG monitoring and exercise testing, methods which complement each other rather than being mutually exclusive, a substantial number of patients with otherwise typical angina pectoris may be found to have silent ischemic episodes. An adequate differentiation between those with symptomatic and those who are asymptomatic based on characterization with respect to age, sex, hypertension, coronary anatomy, etc., has not been successful. Patients with silent ischemia during exercise may also exhibit more episodes of silent ischemia during daily activities and up to 75% of ischemic episodes may be asymptomatic. In general, however, silent ischemia during exercise appears more common than silent ischemia only during daily activities. In the latter case, since there is usually no increase in heart rate, the pathophysiology is regarded as dissimilar from that associated with exercise-induced ischemia. While the presence of silent ischemia appears quite common in patients after acute myocardial infarction, its occurrence, to date, has not been confirmed to carry additional risk, whereas in unstable angina, the association of silent ischemia is indicative of a higher probability of subsequent cardiac events.

Angina Pectoris↗

Localization of the binding site for protein S4 on 16 S ribosomal RNA by chemical and enzymatic probing and primer extension.

We have examined the effect of binding ribosomal protein S4 to 16 S rRNA on the susceptibility of the RNA to a variety of chemical and enzymatic probes. We have used dimethyl sulfate to probe unpaired adenines (at N-1) and cytosines (at N-3), kethoxal to probe unpaired guanines (at N-1 and N-2) and cobra venom (V1) ribonuclease as a probe of base-paired regions of 16 S rRNA. Sites of attack by the probes were identified by primer extension using synthetic oligodeoxynucleotides. Comparison of probing results for naked and S4-bound rRNA shows: Protein S4 protects a relatively compact region of the 5' domain of 16 S rRNA from chemical and enzymatic attack. This region is bounded by nucleotides 27 to 47 and 394 to 556, and has a secondary structure characterized by the junction of five helical elements. Phylogenetically conserved irregular features (bulged nucleotides, internal loops and flanking unpaired nucleotides) and helical phosphodiester bonds of four of the helices are specifically protected in the S4-RNA complex. We conclude that this is the major, and possibly sole region of contact between 16 S rRNA and S4. Many of the S4-dependent changes mimic those observed on assembly of 16 S rRNA into 30 S ribosomal subunits. Binding of S4 causes enhanced chemical reactivity coupled with protection from V1 nuclease outside the S4 junction region in the 530, 720 and 1140 loops. We interpret these results as indicative of loss of structure, and suggest that S4 binding causes disruption of adventitious pairing in these regions, possibly by stabilizing the geometry of the RNA such that these interactions are prevented from forming.

Autoradiography↗

Myocardial ischemia during daily activities and stress.

Twenty-four-hour, 2-channel Holter monitoring during daily activities was performed in 210 patients; during the same day a Bruce protocol treadmill test was also performed and the electrocardiogram was recorded using the same Holter system. Significant ST-segment depression was observed during daily activities in 97 patients, while similar changes were recorded during the treadmill test in 122 patients. Thus, 77% of patients with ST depression during the provocation of the treadmill test had ischemic episodes during their everyday life. On the other hand, 3 patients with proven significant coronary artery disease had spontaneous ischemic episodes during daily activities, but had a negative stress test. The ischemic changes during daily activity developed at a lower heart rate than during stress testing (94 beats/min vs 109 beats/min, respectively, p less than 0.05). A total of 351 ischemic episodes were recorded during daily activities, 241 (69%) of these were asymptomatic. In 46 patients all episodes were asymptomatic, in 15 all were symptomatic, while in 36 both symptomatic and silent episodes were detected. The mean duration of the symptomatic episodes was 13.7 minutes and that of the asymptomatic ones was 14.9 minutes (difference not significant). The degree of ST depression in these 2 groups was also similar. Because of more advanced symptomatology in 143 patients, coronary arteriography was performed; 43 had normal and 100 had pathologic coronary arteries. In this selected group, the sensitivity of Holter monitoring during daily activity was 87% and during stress 97%; the specificity during daily activity was 95% and during stress 88%.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗

Rapid chemical probing of conformation in 16 S ribosomal RNA and 30 S ribosomal subunits using primer extension.

We have investigated in detail the higher-order structure of 16 S ribosomal RNA, both in its naked form and in 30 S ribosomal subunits. Each base in the 16 S rRNA chain has been probed using kethoxal (which reacts with guanine at N1 and N2), dimethylsulfate (which reacts with adenine at N1 and cytosine at N3) and 1-cyclohexyl-3-(2-morpholinoethyl)-carbodiimide metho-p-toluenesulfonate (which reacts with uracil at N3 and guanine at N1). The sites of reaction were identified by primer extension with reverse transcriptase using synthetic oligodeoxynucleotide primers. These results provide a detailed and rigorous experimental test of a model for 16 S rRNA secondary structure, which was derived mainly from comparative sequence analysis. Our data also provide information relevant to tertiary and quaternary structure of 16 S rRNA. Data obtained with naked 16 S rRNA show reasonably close agreement with the proposed model, and data obtained with 30 S subunits show nearly complete agreement. Apart from an apparent overall "tightening" of the structure (in which many weakly reactive bases become unreactive), assembly of the proteins with 16 S rRNA to form 30 S subunits brings about numerous local structural rearrangements, resulting in specific enhancements as well as protections. In many instances, the ribosomal proteins appear to "tune" the 16 S rRNA structure to bring it into accordance with the phylogenetically predicted model, even though the RNA on its own often seems to prefer a different structure in certain regions of the molecule. Extensive protection of conserved, unpaired adenines upon formation of 30 S subunits suggests that they play a special role in the assembly process, possibly providing signals for protein recognition.

Aldehydes↗

Successful non-neurotoxic therapy (without radiation) of a multifocal primary brain lymphoma with a methotrexate, vincristine, and BCNU protocol (DEMOB).

A 3.5-year-old boy with a multifocal primary lymphoma of the brain was treated successfully without neurotoxicity with a treatment regimen that did not include radiation. The protocol of Dexacort (dexamethasone), methotrexate, Oncovin (vincristine), and BCNU (carmustine) (DEMOB), which was developed with the use of MTX pharmacokinetic studies, was given over 7.5 months, and resulted in tumor disappearance on computerized tomography scans and marked improvement in clinical status. The patient remains in good health 3 years after diagnosis (March 1985).

Antineoplastic Combined Chemotherapy Protocols↗

Usefulness of predischarge echocardiographic criteria in predicting complications following acute myocardial infarction.

In 103 patients who recovered from an acute myocardial infarction (AMI) we evaluated the usefulness of predischarge clinical, routine laboratory and M-mode echocardiographic (echo) criteria in predicting cardiac complications during a period of 12-41 months (25.0 +/- 10.7 months) follow-up. The echo parameters evaluated were: left ventricular diastolic diameter, left ventricular percent fractional shortening and the mitral valve E point septal separation. The combination of these three echo criteria was defined as an echo-index, which was considered abnormal if at least two of the three single parameters were pathological. Congestive heart failure occurred in 35 (34%) patients, with significantly higher prevalence among those older than 65 years, with previous AMI and with predischarge findings of heart failure. However, the sensitivity of these clinical parameters was unsatisfactory (34-69%). The sensitivity, specificity and positive predictive value of the echo-index for future heart failure were 89, 88 and 80%, respectively. Chest pain prior to hospital discharge was the only criteria predicting high risk of reinfarction (p = 0.001). The risk of cardiac death was related to age older than 65 years (p = 0.03) and an abnormal echo-index (p = 0.01). The overall mortality rate was 13%, but only 6% among those with normal and 26% among those with pathologic echo-index. In conclusion, in patients who recovered from an AMI, a simple and easily measured echo-index was superior to most clinical and routine laboratory criteria in predicting future heart failure and cardiac death.

Angina Pectoris↗

Reciprocal electrocardiographic changes in acute myocardial infarction.

If reciprocal electrocardiographic changes during acute myocardial infarction (AMI) are a result of ischemia of the wall opposite the AMI, a stress test is expected to induce similar changes in the corresponding electrocardiographic leads. Right atrial pacing was used as a myocardial stress method in 137 consecutive patients recovering from a transmural AMI, and the appearance of pacing-provoked ischemia before hospital discharge was correlated to the presence of absence of ST depression in the opposite wall during the initial 48 hours. Of the 137 patients, 83 (61%) had reciprocal changes; they were more common in inferior (87%) than in anterior (37%) AMI (p less than 0.01). Of 54 patients without reciprocal changes, only 5 (9%) had ST depression during predischarge pacing; however, of the 83 patients with reciprocal changes, 41 had pacing-induced ischemia (p less than 0.01) and 42 did not, indicating that in half of this group the reciprocal changes represent ischemia of the opposite wall. In the other half of the group, without ST depression during pacing, these changes may be a "mirror image" phenomenon. Follow-up showed that angina pectoris, positive treadmill test response 6 months later, or recurrent AMI all consequences of impaired myocardial blood supply, were significantly more frequent in patients with reciprocal changes. This group could be further separated according to the results of right atrial pacing, because angina pectoris or recurrent AMI were infrequent among those with reciprocal changes and negative pacing responses, but was frequent among those with reciprocal changes and positive pacing responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Holter recording during treadmill testing in assessing myocardial ischemic changes.

One hundred forty-four patients underwent a Bruce protocol treadmill exercise test during which an electrocardiogram (ECG) was recorded simultaneously with a 2-channel Holter recorder with bipolar V3- and V5-like leads and by a conventional 12-lead system. Sixty-eight patients had no ST depression on either the Holter or on the 12-lead ECG during the exercise test, whereas in 70 patients ischemic changes were recorded by both methods; thus, in 138 of the 144 patients (96%), the results of the 2 tests were concordant. The severity of ST depression, as judged by the heart rate at which ischemic changes were first noted and the maximal ST depression observed, were similar on both recording systems. The Holter system identified 6 of the 7 patients whose ischemic changes were confined to the inferior wall on the 12-lead ECG. The addition of the V3 lead as a second ischemic lead increased the ischemia detection by 10%. Ninety-five patients also underwent coronary arteriography. In these patients the sensitivity of the Holter system during exercise in detecting significant coronary artery disease was 81% and that of 12-lead ECG was 84%, the specificity was 85% and 85%, respectively, and the positive predictive value 91% and 91%, respectively. Thus, the 2-channel Holter recording system with bipolar V3- and V5-like leads was as accurate as the 12-lead system in detecting ischemic changes during exercise and proved that ambulatory monitoring system can reliably reproduce ST segment.

Adult↗

60-Hz electric fields: detection by female rats.

Female rats were trained to detect a vertical, 60-Hz electric field using the same apparatus and procedure we used previously to study behavioral detection of the field by male rats. Each rat was trained individually to press a lever in the presence of the field and not to press in its absence. Correct detections occasionally produced a food pellet. The probability of detecting the field increased as field strength increased. The threshold of detection--ie, the field strength required for detections at a probability of 0.5 after correction for errors--varied among rats between 3 and 10 kV/m. Behavioral detection by female rats was indistinguishable from that by male rats.

Animals↗

Early right atrial pacing after myocardial infarction. I. Comparison with early treadmill testing.

Right atrial (RA) pacing and modified treadmill testing (TT) were performed in 111 patients recovering from acute myocardial infarction (MI) before hospital discharge to determine whether ischemic responses are more common with RA pacing than with TT and whether the prognosis could be better determined by the results of 1 test compared with the other. Patients with predischarge congestive heart failure, chest pain, physical disability or age older than 70 years were excluded. Ischemic responses were significantly more frequent during RA pacing than during TT (41% vs 34%, p = 0.02). The results of the 2 tests were concordant in 102 patients (92%): Both were positive in 37 and both negative in 65. In 8 patients, results of RA pacing were positive and results of TT were negative; only 1 patient had positive TT and negative RA pacing responses. The higher percentage of positive responses during RA pacing than during TT can be attributed to the significantly higher pressure-rate product achieved during pacing (18,773 vs 16,831 mm Hg/min, p less than 0.001). The ischemic threshold, defined as the pressure-rate product at which an ischemic change was first noted in a particular patient, was almost identical in both tests. During a mean follow-up period of 16 months, 10 patients had recurrent MI; 8 had positive predischarge RA pacing but only 5 had positive TT responses (p = 0.008). Six patients died; in 3 RA pacing responses were positive and in 2 TT responses were positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗