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Biomedical subjects

E Davidson

Publications and source records attributed to E Davidson.

At least 37 records · Page 2Linked to original sources

Tumour-infiltrating lymphocytes and interleukin-2 in treatment of advanced cancer.

Tumour-infiltrating lymphocytes (TIL) were isolated and expanded from small tumour biopsy samples of twenty-eight patients (thirteen with malignant melanoma, seven with renal cell carcinoma, and eight with non-small-cell lung cancer). The patients were treated with autologous expanded TIL (about 10(10)) and continuous infusions of recombinant human interleukin-2(1-3 x 10(6) U/m2 per 24 h). 29% of the patients with renal cell cancer and 23% of those with melanoma achieved objective tumour responses lasting 3-14 months. Toxic side-effects were limited, and no patient required intensive-care monitoring. Adoptive immunotherapy with TIL and interleukin-2 may be an effective systemic approach to the treatment of some patients with malignant melanoma and renal cell carcinoma.

Carcinoma, Renal Cell

[Classification of acute myocardial ischemia by electrocardiography].

Electrocardiographic recording during chest pain is usually performed for detection of myocardial ischemia and localization of the affected area. By analyzing changes in electrocardiograms recorded during chest pain, pathophysiological mechanisms of ischemia, prediction of coronary pathology, and the risk of evolution to myocardial infarction can be determined. Myocardial ischemia is caused by either an increase in O2 demand, reduction in coronary flow, or both. The former is manifested by tachycardia and in such patients measures should be taken to slow the heart rate. Patients with ischemia without tachycardia suffer from reduction of coronary flow and therapy should be aimed at increasing flow. We classify patients with ischemia but without tachycardia according to electrocardiographic patterns recorded during chest pain by precordial leads as follows: group 1, those with ST segment elevation and with positive T waves; group 2, ST segment depression and negative T waves; and group 3, ST depression and positive T waves. Group 1 patients have anterior wall ischemia and the left anterior descending artery is usually involved. They are possible candidates for coronary angiography. In group 2, the electrocardiographic changes reflect extensive subendocardial myocardial ischemia. We found severe coronary artery disease (LMCA or right main artery equivalent) in 69% of such patients, and the mortality in those with subsequent myocardial infarction was 77%, mainly due to pump failure. When this latter electrocardiographic pattern is found, intervention should be prompt, and surgery rather than angioplasty is usually necessary. Patients with ischemic ST depression maximal in V2-V3 should not be included in this group since these changes are reciprocal with posterolateral wall ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris

Atrial fibrillation. Cause and time of onset.

To characterize groups of patients presenting at the emergency room with atrial fibrillation (AF) according to the various causes of AF and the time of its onset, 704 medical files from the Beilinson Medical Center (Petah Tikva, Israel), during an eight-year period, were reviewed. Two thirds of all patients converted to sinus rhythm (SR) within a seven-day in-hospital treatment. The most frequent causes associated with AF were atherosclerotic cardiovascular disease, 55%; rheumatic heart disease, 22.8%; chronic obstructive pulmonary disease, 2.8%; Wolf-Parkinson-White syndrome, 2.6%; and thyrotoxicosis, 2.6%. There was a relatively large group of idiopathic AF (4.5%). Best convertors to SR were patients with idiopathic AF (93.9%), then patients with Wolf-Parkinson-White syndrome (88.8%), followed by atherosclerotic cardiovascular disease (71.6%), and thyrotoxicosis (63.2%). Patients with rheumatic heart disease and chronic obstructive pulmonary disease had the lowest percentage of successful conversion to SR--46% and 55%, respectively. We conclude that there are differences regarding gender, age, and possible conversion of AF to SR according to the different causes of AF.

Aged

Drug-related syncope.

The records of 483 patients admitted to the emergency room because of syncope were reviewed. Forty-one patients were found to have drug-related syncope. Thirty-nine experienced syncope related to drugs administered for cardiovascular disease. The most frequently associated diseases were anginal syndrome (22 patients), hypertension (13 patients), and a history of myocardial infarction (6 patients). Thirty-eight patients experienced symptomatic orthostatic hypotension following drug taking (nitrates in 19 patients, beta blockers in 10 patients, nifedipine in 3 patients, prazosin and quinidine in 2 patients each, methyldopa and verapamil in 1 patient each). One patient developed complete heart block as a result of digoxin intoxication. Two patients developed the characteristic picture of anaphylactic reaction (1 with ampicillin, 1 with dipyrone). During one-year follow-up, without the offending medications, no further syncopal episodes were reported by these patients. We conclude that drug-related syncope was more common among our patients with syncope than had been reported previously. It is suggested that drug-related syncope should be taken into consideration in any patient with syncope who is treated by any of the above-mentioned drugs.

Adult

Inhibition of cryoprecipitation of murine IgG3 anti-dinitrophenyl (DNP) monoclonal antibodies by anionic DNP-amino acid conjugates.

Previously we have demonstrated that eight out of nine IgG3 monoclonal antibodies (mAb) obtained from autoimmune MRL-lpr/lpr mice were able to self-associate and to precipitate in the cold (Gyotoku et al., J. Immunol. 1987. 138:3785). To determine whether the cryoprecipitation of IgG3 mAb is enhanced or inhibited in the presence of specific ligand, we have established eight IgG3 mAb reactive with 2,4-dinitrophenol (DNP) hapten: four mAb were obtained from fusion of spleen cells of C57BL/6 mice immunized with 2,4,6-trinitrophenylated keyhole limpet hemocyanin, three from 129/Sv and one from BALB/c immunized with DNP-lipopolysaccharide. Five of them induced cryoglobulins composed exclusively of the IgG3 mAb. The binding of negatively charged monomeric DNP-amino acid conjugates completely inhibited the cryoprecipitation of all the five cryoprecipitating anti-DNP IgG3 mAb, while the incubation with positively charged or neutral DNP-amino acid conjugates had variable effects: increase, inhibition or no change of the cryoprecipitation. In addition, positively charged DNP-amino acid conjugates were able to induce the cryoprecipitation of one of the non-cryoprecipitating anti-DNP IgG3 mAb. Our data showed that (a) IgG3 mAb derived from non-autoimmune strains of mice, similar to IgG3 mAb derived from an autoimmune MRL-lpr/lpr strain, possessed the unique property to self-associate and were able to form cryoglobulins in most cases; (b) although the Fc-Fc interactions of IgG3 mAb play a decisive role in IgG3 cold solubility, IgG3 cryoprecipitation was markedly influenced after interacting with their specific ligand, depending on the charge of the hapten-amino acid conjugate. This suggested that even minor interferences with the electrostatic equilibrium of the IgG3 by the binding of charged hapten molecules induced dramatic changes in the solubility of the IgG3 mAb at low temperature.

Amino Acids

Does determination of serum aspartate aminotransferase contribute to the diagnosis of acute myocardial infarction?

Values for total lactate dehydrogenase (LD), LD isoenzymes, and serum aspartate aminotransferase (AST) were determined in 150 patients with acute myocardial infarction (AMI) and 130 non-AMI patients 24, 48, and 72 hours after admission. The authors assessed the diagnostic yield of a single determination of AST, LD, and three LD isoenzymes tests: LD-1 greater than LD-2; LD-1 greater than 90 U/L; LD-1/LD greater than 0.4. They also assessed the diagnostic accuracy of combined determination of AST with LD and AST with each of the above three LD isoenzymes tests. The efficiency of single determination of AST was better than that of LD (88% vs. 80%, 48 hours after admission). The most efficient single test for diagnosing AMI was the LD-1 greater than 90 U/L test (92%, 48 hours after admission). The efficiency of the combined AST/LD test was better than that of a single determination of each of the two enzymes (90% vs. 88% and 80%, 48 hours after admission). The highest efficiency was achieved, however, with combined determination of AST and any of the three LD isoenzymes tests. It was found to be more efficient than single determination of each of the LD isoenzymes tests (95.5-96% vs. 89-92.5%) and more efficient than the combined determination of the AST/LD test (95.5-96% vs. 89-90%). The authors conclude that AST should be determined in every patient with suspected AMI because its determination may contribute to the diagnostic yield of LD isoenzymes tests, especially in patients with AMI admitted 48-72 hours after onset of symptoms, when creatine kinase declined to near normal values.

Adult

The cytochrome bc1 complex of Rhodobacter sphaeroides can restore cytochrome c2-independent photosynthetic growth to a Rhodobacter capsulatus mutant lacking cytochrome bc1.

Plasmids encoding the structural genes for the Rhodobacter capsulatus and Rhodobacter sphaeroides cytochrome (cyt) bc1 complexes were introduced into strains of R. capsulatus lacking the cyt bc1 complex, with and without cyt c2. The R. capsulatus merodiploids contained higher than wild-type levels of cyt bc1 complex, as evidenced by immunological and spectroscopic analyses. On the other hand, the R. sphaeroides-R. capsulatus hybrid merodiploids produced only barely detectable amounts of R. sphaeroides cyt bc1 complex in R. capsulatus. Nonetheless, when they contained cyt c2, they were capable of photosynthetic growth, as judged by the sensitivity of this growth to specific inhibitors of the photochemical reaction center and the cyt bc1 complex, such as atrazine, myxothiazol, and stigmatellin. Interestingly, in the absence of cyt c2, although the R. sphaeroides cyt bc1 complex was able to support the photosynthetic growth of a cyt bc1-less mutant of R. capsulatus in rich medium, it was unable to do so when C4 dicarboxylic acids, such as malate and succinate, were used as the sole carbon source. Even this conditional ability of R. sphaeroides cyt bc1 complex to replace that of R. capsulatus for photosynthetic growth suggests that in the latter species the cyt c2-independent rereduction of the reaction center is not due to a structural property unique to the R. capsulatus cyt bc1 complex. Similarly, the inability of R. sphaeroides to exhibit a similar pathway is not due to some inherent property of its cyt bc1 complex.

Carotenoids

Diagnosis and characteristics of lone atrial fibrillation.

Thirty-two patients with LAF were studied. Nineteen (59 percent) were male subjects. Mean age was 46.8 years. They were followed up for 2 to 16 years. On admission, most patients (94 percent) were symptomatic and had palpitations, nine had nonspecific chest pain, and five had syncope or near syncope. Left atrial size measured by echocardiography was less than 40 mm in all patients. During the follow-up period, only one patient had a complication, ie, cerebral embolism. We conclude that LAF may be regarded as a relatively benign form of AF. According to our study, one of its features is left atrial size not larger than 40 mm in echocardiography.

Adult

Lactate dehydrogenase isoenzyme patterns in serum of patients with metastatic liver disease.

Total lactate dehydrogenase (LD, EC 1.1.1.27) and LD isoenzymes were determined in serum of 170 patients with metastatic liver disease, 35 of whom had multiple metastatic sites. Overall, values of LD were above normal for 78% of the 170 patients. Half of the patients had an isomorphic pattern of LD isoenzymes (i.e., relative increase in all five isoenzymes); the other half had an increased LD-4,5 pattern, mostly a solitary increase in LD-5 only. Of those patients with normal LD values, 92% had the increased LD-4,5 pattern, whereas 70% of patients with LD values greater than 350 U/L had an isomorphic pattern of LD isoenzymes. All 35 patients with multiple metastatic sites had LD activity greater than 350 U/L; in the majority of them (74%) it was greater than 500 U/L; in 31 (89%), the increase was isomorphic. The diagnostic efficiency of the combined LD greater than 225 U/L (upper limit of normal) and increased LD-4,5 test results was much better than that of LD greater than 225 U/L alone (93% vs 74%). We conclude that serum LD and LD isoenzymes should be determined in every patient with suspected liver metastatic disease. The isomorphic pattern of LD isoenzymes is apparently associated with higher values for total LD and was common among the patients with multiple metastatic sites.

Aged

Patterns of lactate dehydrogenase isoenzymes 1 and 2 in serum of patients performing an exercise test.

Values for total lactate dehydrogenase (LD, EC 1.1.1.27) activity and LD isoenzymes were determined in serum from 56 patients and 40 healthy subjects before and 24, 48, and 72 h after they performed an exercise test. The mean (for all four times) total LD activity concentration and proportion of LD-2 were within the normal range for all 96 subjects. Mean LD-1 values for serum, although within the normal range in all subjects, were significantly higher in patients with positive exercise test results than in subjects with negative results: 75 (SD 12) U/L in 35 patients with ST depression greater than 2 mm; 63 (SD 14) U/L in 16 patients with ST depression of 1-2 mm; 43 (SD 11) U/L in subjects with negative test results, by 48 h after the test. The LD 1:2 ratio was also markedly higher in the group of patients with positive test exercise results, especially in those with ST depression greater than 2 mm (1.02, SD 0.06), compared with those subjects with negative results (0.60, SD 0.04). A similar trend was also found 24 and 72 h after the exercise test. We conclude that exercise-myocardial ischemia may lead to an increased LD 1:2 ratio in serum, and demonstrate a correlation between the degree of ischemia and the LD 1:2 ratio. Determination of the LD 1:2 ratio, even in the presence of normal total LD activity, may assist in the clinical evaluation of patients performing an exercise test.

Adult

Changes in creatine kinase activity in the course of acute myocardial infarction.

Peak activity of creatine kinase (CK; EC 2.7.3.2) and its decline were determined in 380 patients with acute myocardial infarction (AMI) whose CK values had peaked after admission to the hospital. During hospitalization, 26 patients either died (14 patients) or experienced nonfatal re-infarction (12 patients). In 22 of these 26 patients CK activity decreased by less than 50% within 48 h after the peak value was measured. In all patients who did not die or develop re-infarction, CK activity decreased by greater than 50% during the 48 h after the peak. Evidently the rate of decline of CK (i.e., whether more than or less than 50%) from its peak value during the 48 h after AMI may be helpful in assessing which patients are at high risk for developing re-infarction or dying.

Adult

Elevated serum creatine kinase levels. An early diagnostic sign of acute dissection of the aorta.

Twenty-two patients suffering from acute dissection of the aorta were analyzed for their serum creatine kinase levels within six hours of onset of acute chest pain. Elevated serum levels were found in 14 patients (64%). In five patients, creatine kinase isoenzyme analysis was performed. These five patients showed more than 95% creatine phosphokinase MM isoenzyme of the total creatine kinase level. The finding of elevated levels of total creatine kinase in patients presenting with acute chest pain does not exclude acute dissection of the aorta. Determination of creatine kinase isoenzymes may be helpful in the differential diagnosis of acute chest pain.

Adult

Dexamethasone and indomethacin do not affect brain edema following head injury in rats.

Head trauma was induced in rats by a weight-drop device, falling over the exposed skull over the left hemisphere. The neurological state of the rats was evaluated by a neurological severity score at 1 h and 18 h post head trauma. At 18 h post head trauma, rats were decapitated and tissue from the vicinity of the injury and from a corresponding area in the contralateral hemisphere was taken for specific gravity (SG) determination using linear gradient columns. Slices were taken from the same sites for incubation in Krebs-Ringer solution, and the concentrations of prostaglandin (PG)E2, 6-keto-PGF1 alpha, and thromboxane B2 accumulated in the medium during 1 h were measured by radioimmunoassay. In one experimental group, rats were pretreated with intraperitoneal dexamethasone sodium phosphate (4 mg/kg) 18 and 2 h before head trauma, and a third dose was given 8 h post head trauma. Another group was treated with intraperitoneal indomethacin (10 mg/kg) 1 h before and 7 h after head trauma. Other groups were treated immediately and 8 h after head trauma with 4, 8, 15, or 30 mg/kg of dexamethasone sodium phosphate. Another group of rats was treated with free dexamethasone (10 mg/kg) right after head trauma and 8 h later. Head trauma induced edema, as expressed by decreased SG, in the left hemisphere of all traumatized rats. Neither treatment protocol affected the neurological severity score of the injured rats or the SG of the contused hemisphere. PG synthesis, on the other hand, was significantly reduced following indomethacin or free dexamethasone, both in sham and traumatized rats, but not in dexamethasone sodium phosphate-treated rats. We conclude that pretreatment with indomethacin, dexamethasone sodium phosphate, or dexamethasone, used in the present protocols, does not affect posttraumatic cerebral edema. Thus, the role of PGs as mediators of edema formation remains unclear.

Animals

Total lactate dehydrogenase and its isoenzymes in serum of patients with non-small-cell lung cancer.

Values for total lactate dehydrogenase (LD, EC 1.1.1.27) activity in serum and LD isoenzymes were determined at diagnosis in 273 patients with non-small-cell lung cancer, 85 of whom were in stage 1, 92 in stage 2, and 96 in stage 3. We divided the patients into three groups, based on their total serum LD values: less than 225 U/L (normal reference range), 226-500 U/L, and greater than 500 U/L. Overall values for LD were above normal at diagnosis for 69% of the patients, being moderately increased in 63 patients and highly increased in 125. Eighty percent of the patients in stage 1 had normal values for LD at diagnosis, but 88% of the patients in stage 2 and 94% of the patients in stage 3 had above-normal LD values at diagnosis. In 55% of the patients in stage 2 and 73% of the patients in stage 3, LD activity was highly increased. In the patients with normal values for total LD, the proportions of the LD isoenzymes were normal. In the patients with increased LD, the isoenzyme proportions were increased for LD-4 and LD-5, up to twice the normal values. The sensitivity of LD in detection of lung cancer was 60% for LD at the cutoff point of 250 U/L in comparison with normal controls, and 47% for LD at the cutoff point of 310 U/L in comparison with the benign lung disease group of patients (95% specificity). We conclude that total LD in serum may be a direct indicator of clinical stage and tumor burden in patients with non-small-cell lung cancer.

Adenocarcinoma

Atypical patterns of lactate dehydrogenase isoenzymes in acute myocardial infarction.

Total lactate dehydrogenase (LD; EC 1.1.1.27) activity in serum and LD isoenzymes were quantified in 190 patients with acute myocardial infarction (AMI) 24, 48, and 72 h after admission. In 90% of the 570 blood specimens an LD isoenzyme pattern typical of AMI (LD-1/LD-2 greater than 0.76) was found. The other 56 blood specimens showed an LD isoenzyme pattern atypical of AMI (LD-1/LD-2 less than 0.76). They were divided into three groups: 28 specimens with isomorphic pattern (relative increase in all five LD isoenzymes); 18 with relatively increased LD-3 proportion (greater than 35%); and 10 specimens with increased LD-5 proportion (greater than 10%). No difference was found in mean total LD activity in serum between the typical isoenzyme group and the three atypical groups. The LD isomorphic pattern was found in 60% of AMI patients complicated by cardiogenic shock. Fifty percent of AMI patients admitted with pulmonary edema showed increased LD-3 proportion and half of the patients with AMI and congestive heart failure, predominant right, demonstrated increased LD-5 proportion. We conclude that although most patients with AMI present at diagnosis with a typical LD isoenzyme pattern, it is important to recognize that some may present with atypical LD isoenzyme patterns, which may be associated with specific AMI complications.

Adult

Significance of isolated increases in total lactate dehydrogenase and its isoenzymes in serum of patients with bacterial pneumonia.

Total lactate dehydrogenase (LD, EC 1.1.1.27) activity in serum and LD isoenzymes were quantified at the time of diagnosis in 320 patients with bacterial pneumonia. In eighty, LD activity was increased, but this was accompanied by either other pathological results for liver-function tests or associated diseases that could explain it. The remaining 240 patients were divided into four groups, based on their total serum LD values: group A, less than 225 U/L (normal limit); group B, 226-350 U/L; group C, 351-499 U/L; and group D, greater than 500 U/L. Total LD was above normal at diagnosis in 40% of the patients. Recovery time was twice as long in group D as in groups A, B, and C. In five patients from group D, the pneumonia reflected underlying lung cancer. In groups B and C, the LD-3 ratio was increased in comparison with group A; in group D, LD-4 and LD-5 were increased up to twice the normal limit. Evidently nearly half of patients with bacterial pneumonia may show isolated increases in total LD activity (mostly LD-3) in serum. In cases with high activity, prolonged recovery time is expected. Intensive follow-up and extensive investigation are warranted in these patients, because some may have underlying lung cancer.

Aged