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Biomedical subjects

E C Lynch

Publications and source records attributed to E C Lynch.

At least 19 recordsLinked to original sources

Functional importance of sequence in the stem-loop of a transcription terminator.

Intrinsic transcription terminators of prokaryotes are distinguished by a common RNA motif: a stem-loop structure high in guanine and cytosine content, followed by multiple uridine residues. Models explaining intrinsic terminators postulate that the stem-loop sequence is necessary only to form structure. In the tR2 terminator of coliphage lambda, single-nucleotide changes reducing potential RNA stem stability eliminated tR2 activity, and a compensatory change that restored the stem structure restored terminator activity. However, multiple changes in the stem sequence that should have either maintained or increased stability reduced terminator activity. These results suggest that the ability of the stem-loop structure to signal transcription termination depends on sequence specificity and secondary structure.

Bacteriophage lambda

Ringed sideroblasts in primary myelodysplasia. Leukemic propensity and prognostic factors.

Among 123 patients with ringed sideroblasts on bone marrow aspirates, 85 had acquired ringed sideroblasts with primary myelodysplasia. The patients were placed in categories modified from the French-American-British classification based on percentages of ringed sideroblasts and myeloblasts in the initial bone marrow. Overall, 48% (41/85) of patients with myelodysplasia developed acute leukemia. Primary acquired sideroblastic anemia was the most favorable category with longer survival and 13.8% (4/29) leukemic conversions. Variables correlating with leukemic transformation included male sex, thrombocytopenia, neutropenia, and pseudo-Pelger-Huët neutrophils. Only two variables had independent predictive value by multivariate regression analysis: a high percentage of myeloblasts and a low percentage of ringed sideroblasts. Numerous ringed sideroblasts strongly predicts a more favorable course in myelodysplastic patients.

Acute Disease

Culture as a determinant of "humanistic traits" in medical residents.

In this cross-cultural study of Puerto Rican and Texas physicians, we have tested the hypothesis that physicians' "humanistic attributes" are culturally related. Differences (P = .05 to .01) were found between mean responses of the two groups of residents to seven of the questions on the Totalitarian-Authoritarian-Dogmatism scale. Factor analysis determined that the two principal components of disagreement were medical political and ethical issues (P = .001) but not patients and their problems. Faculty responses provided additional evidence that customs and traditions influence how professional subgroups manifest attitudes: Puerto Rican faculty rated residents highest on "humanistic traits" if they self-reported high ethical scores, and lowest if they self-reported high radical scores; Baylor faculty reflected the "age-drag" on changing values by differing (P = .05 to .001) from both groups of residents on 38% of the questions. The difficulty of rating residents with a universal standard of "humanistic traits" is supported by the culture and age-specific differences reported herein.

Attitude of Health Personnel

Measuring "humanism" in medical residents.

The American Board of Internal Medicine (ABIM) has charged directors of residency programs with evaluating "humanistic attributes" in residents seeking certification. To investigate whether traditional measures of residents' performance assess humanistic attributes, 38 second- and third-year medical residents completed the Totalitarian-Authoritarian-Dogmatism (TAD) and Rokeach tests for attitudinal assessment. Five primary sources were used to measure performance. When the measures of performance and attitude were correlated, two negative correlations with "antipathy toward patients" were found: professional maturity (r = -.43, P less than .01) and compassion and concern for patients (r = -.35, P less than .04). The TAD Opinionnaire and the special performance evaluation detect "nonhumanistic dimensions" that routine faculty assessments do not. Since the new Likert scale distributed by ABIM does not differ materially from the rating form used at Baylor for 2 1/2 years, it is unlikely that "humanistic attributes" will be measured by the ABIM's new scale.

Attitude of Health Personnel

Plasma cell dyscrasia with marrow fibrosis. Clinicopathologic syndrome.

Five new cases of plasma cell dyscrasia with coexistent myelofibrosis are described and six previously reported cases are reviewed. Four of the new patients and two from the literature had features of a previously unrecognized syndrome. This syndrome was characterized by significant paraprotein levels, marked marrow fibrosis, and plasmacytosis, without features of extramedullary hematopoiesis (agnogenic myeloid metaplasia) and leukoerythroblastosis. These patients were generally severely anemic and commonly leukopenic and thrombocytopenic. In contrast, one of the new patients and four in the literature showed classic features of the myeloproliferative disease, myelofibrosis with agnogenic myeloid metaplasia, along with features of typical multiple myeloma.

Aged

Autoimmune hemolytic anemia and carcinoma: an unusual association.

Four patients with Coombs'-positive hemolytic anemia associated with carcinoma are presented and compared to 12 previously described patients. These patients commonly seek medical attention for symptoms of anemia rather than for complaints due to the tumor mass. The physician should particularly evaluate for an underlying carcinoma when a patient over the age of 60 years presents with autoimmune hemolytic anemia. Autoimmune hemolytic disease has been demonstrated in patients with a wide variety of tumors, including squamous cell carcinomas, adenocarcinomas, hypernephromas, oat cell carcinomas and a seminoma. Corticosteroid treatment is less effective in autoimmune hemolytic disease associated with carcinoma than in idiopathic autoimmune hemolysis. Tumor extirpation in patients with localized neoplastic disease may abolish the autoimmune hemolytic anemia. Control of the carcinoma through irradiation and chemotherapy together with corticosteroid therapy and/or splenectomy lessened the anemia in some patients. The positive Coombs' test may revert to negative with tumor excision or control. Subsequently, the positivity of the Coombs' reaction may provide a clue to recurrent neoplastic activity. The pathogenic mechanism underlying the association between carcinoma and autoimmune hemolytic disease is poorly understood.

Adenocarcinoma

Acute renal failure in patients with acute leukemia.

Acute renal failure may be a contributory cause of death in patients with acute leukemia. The purpose of this study was to define the causes and course of acute renal failure in group of patients with acute leukemia in order to identify preventive measures and reversible aspects of the renal insufficiency. Among 88 patients with acute leukemia whose courses were followed to the time of death, ten developed acute renal failure. Etiologic factors of the renal failure were uric acid nephropathy, sepsis with complicating hypotension and hypovolemia, and the administration of nephrotoxic antibiotics. In one patient ureteral obstruction from clots was responsible for renal failure, while in another patient disseminated aspergillosis led to renal failure. Other causes of acute renal failure in persons with acute leukemia, but not observed in this patient group, are hypercalcemia and leukemic infiltration of the kidneys.

Acute Disease

Forty-one variables following thoracotomy in calves.

Seven calves underwent thoracotomy to study the response of 41 physiologic variables over a 14 day post-operative period for comparison to a recent series of left ventricular bypass pump implants. The experimental protocols were identical to the pump implant protocols except that the sham operated animals did not receive antiplatelet or anticoagulant drugs and the pumps were not implanted. Of the 41 variables studied, 13 changed significantly during the post-operative period. Heart rate, hematocrit, whole blood hemoglobin, and fibrinogen concentration decreased, while fibrinogen survival, stroke volume, cardiac output, arterial blood pH, pCO2 and pO2, plasma sodium concentration, and urinary excretion rates of sodium and potassium increased from the first or second to the fourteenth post-operative day. Heart rate and hematocrit also decreased in the recent series of 18 animals in which left ventricular bypass pumps were implanted. The decrease in heart rate is toward the unoperated control value as the calves recover from the operative stress. The decrease in hematocrit is probably the result of daily removal of blood for the physiologic studies because there was no evidence of hemorrhage or red blood cell destruction.

Animals

Prednisone-responsive congenital erythroid hypoplasia.

A 24-year-old woman had congenital hypoplastic anemia (Blackfan-Diamond syndrome). Anemia was discovered at the age of 12 months and persisted thereafter. The patient had associated congenital abnormalities of urethral stricture, hypoplastic thumb, and absent radial pulse. Her erythroid hypoplasia responded favorably to treatment with prednisone.

Adolescent

Fragility of abnormal erythrocytes evaluated by response to shear stress.

Shear stress is a potential cause of erythrocyte fragmentation and hemolysis in flowing blood. In this study, the response of abnormal human erythrocytes to shear stress in virto was evaluated using a concentric cylinder viscometer. Compared to normal red cells, deoxygenated erythrocytes from persons with sicle cell anemia were particularly susceptible to fragmentation and hemolysis by shear stress. Oxygenation of sicke cell blood improved the resistance of those red cells to shear stress; they remain, however, more susceptible to shear stress than normal erythrocytes. Erythrocytes from patients with iron deficiency, thalassemia minor, and erythrocyte pyruvate kinase deficiency showed fragmentation and hemolysis at threshold shear stresses intermediate between those ovserved for blood from patients with sickle cell anemia and normal persons. Blood samples from patients with hereditary spherocytosis were more resistant to shear stress than normal blood. These results indicate that there are important differences in the response of various red cells to shear stress.

Anemia, Hypochromic

Red blood cell damage by shear stress.

A series of careful studies has been made on blood damage in a rotational viscometer. Specific attention has been focused on the effects of solid surface interaction, centrifugal force, air interface interaction, mixing of sheared and unsheared layers, cell-cell interaction, and viscous heating. The results show that there is a threshold shear stress, 1500 dynes/cm(2), above which extensive cell damage is directly due to shear stress, and the various secondary effects listed above are negligible. By analysis of these results and those of prior workers it is shown that the exposure time-shear stress plane is divided into two distinct regimes. In the regime of relatively low stresses and exposure times there is relatively little damage, and the damage is dominated by solid surface interaction effects. In the other regime, at high stresses and exposure times, stress effects alone dominate and very high rates of hemolysis occur. The experimental findings of all prior workers are shown to be consistent when interpreted in this way.

Centrifugation