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Biomedical subjects

D A Bergman

Publications and source records attributed to D A Bergman.

At least 37 records · Page 2Linked to original sources

Effects of thermodynamic nonideality on the kinetics of ester hydrolysis by alpha-chymotrypsin: a model system with preexistence of the isomerization equilibrium.

The effects of a small inert solute, sucrose, on the kinetics of hydrolysis of N-acetyl-tryptophan ethyl ester by bovine alpha-chymotrypsin have been investigated. In studies at pH 7 and 20 degrees C the presence of 0.5 M sucrose in assay mixtures caused no discernible change in kinetic parameters, a result consistent with existence of the enzyme in a single conformational state under those conditions. However, at pH 3.5 and 50 degrees C, conditions under which the enzyme comprises an equilibrium mixture of compact and expanded isomeric states, inclusion of the inert solute led to a considerable decrease in Michaelis constant (0.84 to 0.61 mM) but no significant change in maximal velocity. These results were shown to be amenable to quantitative interpretation in terms of thermodynamic nonideality effects on catalysis by an enzyme undergoing reversible isomerization in the absence of substrate. For that analysis, which required experimental estimates of the equilibrium constant for preexisting isomerization of enzyme and the activity coefficient of substrate, the magnitude of the former (0.3) was obtained by difference spectroscopy: liquid-liquid partition studies with bromobenzene as organic phase were used to determine the effect of sucrose on the activity coefficient of N-acetyltryptophan ethyl ester. Such agreement between experimental kinetic findings and theoretical predictions based on considerations of excluded volume points to the possible use of the space-filling effects of small solutes for delineating the gross extent of conformational changes associated with reversible isomerization of proteins, and hence to the potential of thermodynamic nonideality as a probe for studying protein denaturation mechanisms as well as substrate-mediated changes associated with enzyme reaction mechanisms.

Chymotrypsin↗

Allowance for "analyte valence" in the retention model of ion-exchange chromatography. Studies of adenosine 5'-phosphates on DEAE cellulose.

Quantitative expressions are derived for various retention models of the ion-exchange behaviour of multivalent analytes. Their effectiveness as descriptions of experimental results is then tested by application to partition equilibrium studies of the effect of phosphate concentration on the interaction between the three adenosine 5'-phosphates and diethylaminoethylcellulose at pH 4.4. A completely general multi-state model has pointed to quantitative deficiencies in the currently accepted cooperative two-state model, which is, however, superior to a multi-state model devoid of cooperative effects. A similar situation pertains to the ion-exchange behaviour of cytochrome c on carboxymethylcellulose at pH 7.0.

Adenosine Diphosphate↗

Quantitative affinity chromatography: increased versatility of the technique for studies of ligand binding.

The potential of affinity chromatography for the characterization of strong solute-ligand interactions is explored by studying the NADH-dependent elution of rabbit muscle lactate dehydrogenase from a column of trinitrophenyl-Sepharose in 0.067 M phosphate, pH 7.2. An interesting development is the simplification of the general affinity chromatography theory that emanates from the use of affinity matrices with a high concentration of immobilized reactant groups. The resultant expression allows evaluation of the intrinsic association constant for solute-ligand interactions from a single series of either zonal or frontal affinity chromatographic experiments conducted in the presence of a range of free ligand concentrations. Thus, contrary to previous belief, an affinity matrix designed for solute purification work should prove to be an asset for, rather than an impediment to, the study of solute-ligand interactions by quantitative affinity chromatography.

Adsorption↗

The impact of reading a clinical study on treatment decisions of physicians and residents.

The study presented here reports on the impact of newly published clinical research on physicians' decisions. Eighty-three pediatricians, pediatric residents, and family practitioners were presented with a common, potentially serious problem, an infant with a high fever, and were required to estimate the probabilities of bacteremia and of acquiring meningitis and to choose from management options. The participants then read a published scientific report addressing the risks of meningitis in febrile infants and were asked afterward to answer again the questions relating to the clinical problem. After reading the study, the participants significantly increased their probability estimates of the patient acquiring meningitis. Only 14 percent of the participants would have hospitalized the patient before reading the article, but 47 percent would have done so after reading the article. Pediatricians were more likely than family practitioners to use antibiotics after reading the article. These decisions were not based not based on logical processing of information, as there was no correlation between the physicians' estimate of the risk of meningitis and the underlying risk of bacteremia and no correlation between the participants' decisions to hospitalize or use antibiotics and their estimated risk of the patient developing meningitis. Physicians appear to have considerable difficulty in using probability data and appear to base estimates of serious disease and subsequent management on intuition rather than calculation.

California↗

Using structured medical information to improve students' problem-solving performance.

In the study reported here, the authors assessed the use of efficient organization of knowledge and of problem-solving strategies to enhance medical students' clinical problem-solving skills. Thirty-five preclinical medical students were randomly assigned to a experimental or control group and given a knowledge base containing information on eight congenital heart diseases to learn. Information for the experimental group emphasized disease groupings (based on their similar clinical presentation), symptom-disease associations, and clinical problem-solving heuristics. The same information for the control group was presented in a textbook format that emphasized the pathophysiology of the diseases. The students then diagnosed three computerized diagnostic problems of varying difficulty while verbalizing their problem-solving strategies. The results showed that the experimental group acquired a higher ratio of diagnostic to nondiagnostic cues, mentioned the correct diagnosis sooner in their workups, and correctly diagnosed the most difficult case more often than the control group. These results provide support for revisions in the organization and presentation of information that are aimed at improving clinical problem-solving skills.

Clinical Competence↗

Bilateral intracavernous carotid aneurysms mimicking a prolactin-secreting pituitary tumor.

The triad of hyperprolactinemia, ophthalmoplegia, and radiologic abnormalities of the sell turcica suggest a tumor in the area of the pituitary gland. A new association--bilateral intracavernous carotid aneurysms--is presented. Two elderly women had extraocular muscle palsies and elevated serum prolactin levels of 71 and 32 ng/ml (normal: less than 20 ng/ml). In the former, a high-resolution computed tomography scan made after contrast medium injection was incorrectly interpreted as demonstrating a pituitary tumor; cerebral arteriography revealed bilateral aneurysms. In the other patient, a computed tomography scan after contrast medium injection demonstrated the bilateral aneurysms, and these were confirmed by radionuclide angiography.

Aged↗

Urinary tract infection in infants with unexplained fever: a collaborative study.

Nine centers collaborated to determine the rate of urinary tract infection in infants with unexplained fever, to determine whether the rate is higher in febrile infants than in asymptomatic infants, and whether the yield justifies urine cultures in febrile infants. Urine cultures were done in 501 infants 0 to 2 years of age. The rate of confirmed urinary tract infections in the 193 febrile infants was 4.1%. All infections were in girls, with a rate of 7.4%. The rate of confirmed urinary tract infections in the 312 asymptomatic infants was 0.3%; again, all infections were in girls, with a rate of 0.7%. The rate in febrile girls was significantly higher than the rate in asymptomatic girls (P less than 0.01). The data support the advisability of culturing the urine of infant girls with unexplained fever.

Acute Disease↗

Analysis of a program for mental health referrals from a pediatric clinic.

A behavioral evaluation and referral unit (BERU) was established in a Children and Youth Project, to facilitate the referral of children with learning and behavioral problems that were beyond the scope of the general pediatrician. The BERU assessed the need for referral, determined the most appropriate receiving agency, initiated the appointment, and ascertained if the appointment was kept. Results of the program revealed that 48% of referrals to BERU were referred outside the Children and Youth Project. Eighty-four percent of this group completed their referral. Sixty percent received additional care either within or outside the Children and Youth Project. BERU evaluation was required for 25% of behavioral and learning problems presenting in a general pediatric clinic.

Adolescent↗

"The new morbidities," physician competence, and consumer utilization.

Results of a questionnaire assessing pediatricians' perceived competence regarding psychosocial, developmental and traditional medical problems were analyzed. The data were compared with a similar questionnaire distributed to seventh grade teachers, youth and parents assessing problems for which pediatricians were utilized. The results reveal that pediatricians rate their competency higher in the area of traditional medical problems. The implications of this study are discussed.

Attitude↗