Respiration and glucose oxidation in human and guinea pig leukocytes: comparative studies.

A comparison has been made of the metabolic shifts in human and guinea pig leukocytes when they phagocytize. Respiration of guinea pig polymorphonuclear leukocytes (PMN) and the increment during phagocytosis were each about 2(1/2)-fold that of human PMN. This was also true of the direct oxidation of glucose-6-P (hexose monophosphate shunt). Enzymes potentially responsible for these phenomena have been compared in each species. Cyanide-insensitive NADH oxidase and NADPH oxidase were measured and only the formed exhibited adequate activity to account for the respiratory stimulus durintg phagocytosis. The hydrogen peroxide formed by this enzyme stimulates the hexose monophosphate shunt by oxidizing glutathione which upon reduction by an NADPH-linked glutathione reductase provides NADP to drive the hexose monophosphate shunt. Other linkages between respiratory stimulation and that of the hexose monophosphate shunt also pertain in the guinea pig.

Primary position upbeat nystagmus. A clinicopathologic study.

Eye movements were studied with electro-oculography in a patient with primary position, large amplitude, upbeat nystagmus. The upbeat nystagmus increased in amplitude on upward gaze, decreased on downward gaze, and was not altered by loss of fixation. The patient could not produce smooth pursuit movements upward or to the left, but had normal saccadic and vestibular induced eye movements in all directions. At necropsy, a low grade glioma was found involving primarily the medulla and caudal pons. The inferior olives and prepositus hypoglossal nuclei were diffusely infiltrated with tumor. These results suggest (1) primary position upbeat nystagmus is due to a defect in the upward smooth pursuit system, (2) the lower brain stem at the level of the inferior olives and nucleus prepositus hypoglossi is important in the mediation of vertical pursuit, and (3) primary position upbeat nystagmus can result from damage to several nuclei and interconnecting pathways in the caudal brain stem and midline cerebellum involved in control of vertical smooth pursuit.

2-Benzazepines. 2. Thiazolo[5,4-d][2]benzazepines.

As part of a program in the area of annelated 2-benzazepines, several thiazolo[5,4-d))[2]benzazepines were prepared. Treatment of the bromo ketones 7-9 with various thio amides gave the thiazoles 10-15, which when treated with methylamine gave the title compounds. The preliminary pharmacology of these compounds showed that they had central nervous system activity similar to the 1,4-benzodiazepines, such as diazepam. The thiazolo[5,4-d][2]benzazepines were also found to bind to the benzodiazepine-receptor complex, indicating that their pharmacological actions are probably related to the 1,4-benzodiazepines.

2-benzazepines. 5. Synthesis of pyrimido[5,4-d][2]benzazepines and their evaluation as anxiolytic agents.

A series of 5H-pyrimido[5,4-d][2]benzazepines has been synthesized, starting from the corresponding 2-benzazepin-5-ones, and evaluated as potential anxiolytic agents. Selected compounds from this series show a pharmacological profile of action different than that of diazepam. They are more potent than diazepam in the anti-pentylenetetrazole test and in the [3H]diazepam binding assay, yet show less activity in the inclined screen test. A pharmacological data profile is given for 9-chloro-7-(2-chlorophenyl)-5H-pyrimido[5,4-d] [2]benzazepine (7c). The structure-activity relationships of these potential anxiolytic agents are discussed.

Fatty acids. Part 48. 13C nuclear magnetic resonance studies of acetylenic fatty acids.

The 13C NMR spectra of thirty-seven alkynoic acids (C8-C18) and ten alkadiynoic acids (C18 and C20) are reported and interpreted. The influence of COOH, COOCH3, CH3, and C identical to C groups on the chemical shifts of nearby carbon atoms is assessed. These influences are largely additive so that available spectra are readily interpreted and the spectra of new compounds of this type can be predicted. These preliminary results indicate that 13C NMR spectroscopy should be of considerable value in the structural identification of acetylenic compounds.

Access to data and the information explosion: oral contraceptives and risk of cancer.

This report describes a technically feasible method to deal with the enormous volume of literature published regarding oral contraceptives. This subject was discussed in 3735 publications during the period from November 1977 through October 1980. Our findings showed that those papers reporting original, numeric relationships involving risk of cancer and use of oral contraceptives were one percent of the total 3735 publications. However, only seven of the 27 articles involved were authored by individuals from departments of obstetrics and gynecology. Further, only four of the 27 were published in journals devoted to obstetrics and gynecology. The analyses suggest a form of censorship taking place, in that the obstetrics/gynecology specialists do not have ready access to the primary data.

PIP: Effective decision making necessitates access to pertinent data. Because of information explosion, however, the mechanisms used in the literature review process can overwhelm a researcher or a practitioner. This paper describes a technically feasible method for dealing with a current large volume situation using the subjects oral contraceptives and risk of cancer as examples. The National Library of Medicine's MEDLARS system identified 3735 citations covering the period November 1977 through October 1980 at the time of the survey. It was found that papers reporting original numeric relationships involving risk of cancer and use of oral contraceptives were 1% of the 3735 publications and only 7 of 27 articles involved were authored by individuals from depts. of obstetrics and gynecology. Only 4 of the 27 were published in the obstetric/gynecology journals, suggesting that obstetricians/gynecologists are not having ready access to primary data. The authors therefore recommended an information processing technique which separates the analysis into 2 parts: 1) the mechanical, performed by the technician; and 2) the cognitive, performed by the professional. The technician examines the cited article and classifies it relative to the presence of numeric displays, originality of work reported, and inclusion of data of interest to the professional. The cognitive functions are left to the professionals. This process provides relevant articles and identifies verifiable reasons for excluding others. It is also effective in terms of cost and time. In this survey, the retrieval; analysis; and photocopying took 14 days or 112 hours. In contrast, the professional time traditionally spent in reviewing citations before the retrieval process begins is about 7 hours (given 741 citations containing 250,000 words and reading time of 600 words per/minute. Also, the accuracy of selections using the title; abstract; and indexing terms is questionable given the variable nature of matching author's and user's purposes and the presence of specific indexing terms and the relationships of interest to the user. The literature search and analysis described in this paper is particularly effective in isolating articles with relevant data directed to different medical groups.

Effect of magnetic doping on the electronic states of Ni.

Angle-resolved photoemission is used to determine the change in the electronic states of Ni induced by doping with Fe and Cr. Well-defined spin and k states are selected using high energy and k resolution combined with single crystal alloys. Iron suppresses the mean free path of minority spins only, while chromium suppresses both spins and decreases the magnetic splitting. The strong variation of these effects from one impurity to the other supports the concept of magnetic doping.

Determining educational needs in the physician's office.

Techniques to identify educational needs from real events in office practice are usually unwieldy, intrusive, and expensive. We are developing an approach based on review and analysis of individual physicians' prescriptions. This technique imposes little additional effort on the participating physician, yet effectively identifies problems in drug prescribing that can lead to specific educational remedies. Experience with 44 physicians using the system shows wide variation in prescribing practices as well as in the needs identified. The problems can be grouped into seven major categories: inappropriate indications; excessively frequent prescriptions for certain drugs; prescription of drugs with abuse potential; inadequate instructions; excessive dosage, especially in elderly patients; prescription of ineffective drugs; and potential drug interactions. The method offers promise as a component of an individualized guidance system linking continuing medical education with actual medical practice.

Quinazolines and 1,4-benzodiazepines. 92. Conformational recognition of the receptor by 1,4-benzodiazepines.

We propose that the conformation of 1,4-benzodiazepines that is recognized by the binding site on the benzodiazepine receptor complex is one in which the planes formed by the fused benzene ring and the methylene group (and the two adjoining atoms) of the diazepine ring are in the R configuration. The derivation of this conformation was based on comparisons of computer-generated 3-dimensional structures obtained from single-crystal X-ray data for diazepam, (R)- and (S)-1,3-dimethyl-5-(2-fluorophenyl)-7-nitro-1,3-dihydro-2H-1,4-benzodiazepin-2- one, and the structurally rigid ethyl (S)-7-chloro-11,12,13,13 alpha-tetrahydro-9-oxo-9H-imidazo[1,5-alpha] pyrrolo[2,1-d][1,4]benzodiazepine-1-carboxylate. The affinity of ligands for the benzodiazepine binding site was determined using the [3H]-diazepam binding assay.

Continuing education and library services for physicians in office practice.

A program is described which incorporates library services into continuing medical education for physicians. The educational service is based on the actual needs of the physician rather than on his perceived needs. The needs assessment is accomplished by reviewing drug-prescribing habits. Current medical literature is then selected for the physician to coincide with his unique educational needs. The program is further designed to evaluate the change in the physician's drug-prescribing habits as a result of his study of the literature received.

Step-induced frustration of antiferromagnetic order in Mn on Fe(001).

We studied the spin arrangement in ultrathin antiferromagnetic Mn films in contact with a ferromagnetic Fe(001) substrate using spin-polarized scanning tunneling microscopy. Mn shows a layerwise antiferromagnetic order on Fe(001). In regions where Mn overgrows Fe steps, a frustration of the antiferromagnetic order occurs which is similar to a 180 degrees domain wall. This topologically enforced frustration was studied as a function of Mn thickness. A linear increase of the width of the frustration region with the Mn thickness was found.

Changing prescribing practices through individual continuing education.

In a study involving 94 practicing physicians, committees of clinical pharmacologists analyzed copies of prescriptions (and additional relevant clinical data) to identify problems in prescribing ("educational needs"). Only the ten most commonly prescribed drugs were studied in the samples of 200 prescriptions from each physician; 1061 problems were identified in the prescriptions of the 94 participants. One physician group (n = 41) received feedback (instructional packets) addressing specific problems in prescribing; a second sample consisting of 200 prescriptions was then collected and analyzed. The physicians in this group changed their prescribing practices 30% of the time in accordance with recommendations, whereas those in the group that received no educational feedback changed in only 3% of the cases. When a physician stated an intention to change, an actual change resulted 50% of the time. Individualized teaching in response to real events in practice is a practical and effective method of improving physician performance.

A method of self-directed learning in continuing medical education with implications for recertification.

A method of self-directed learning for physicians that can be used to satisfy a portion of specialty board recertification requirements integrates contract learning (self-formulated learning plans), information brokering (linking physicians with consultants and community resources), and collegial networking (discussion groups). The method encourages physicians to focus on educational objectives, supplies learning resources, and promotes interactions with colleagues in study groups. Fifty-nine (53%) of the 102 learning goals update physicians' knowledge. Print sources and discussions with experts were the commonest resources used. Forty-five (49%) of 91 participants completed their learning plans. Forty-nine (74%) completed projects were judged successful in achieving their goals. Twenty-five (45%) of 56 physicians responding to a questionnaire stated that the method was superior to traditional continuing medical education. Fifty-two percent of the participants found the method as effective as traditional continuing medical education. Proof of accomplishment allows the method to be used as part of a specialty board recertification process.

Epidemiologic aspects of a St. Louis encephalitis outbreak in Mesa County, Colorado.

An epidemic of St. Louis encephalitis in 1985 in Mesa County, Colorado, led to 17 cases, including one fatality. Risk was associated with advanced age and residence in Grand Junction, the county's principal city. A trend was observed toward higher risk in females. However, increased risk in females was not associated with higher infection rates (increased exposure). Capture enzyme immunoassays detected specific immunoglobulin M (IgM) and immunoglobulin A after infection. A serosurvey of Grand Junction residents disclosed an infection rate of 4.0%, indicating that 1,123 epidemic St. Louis encephalitis infections may have occurred in the city. Evidence of previous St. Louis encephalitis virus infection was found in 11.2% of survey respondents who had neutralizing antibody to the virus without specific IgM. The prevalence of St. Louis encephalitis virus antibody was similar to rates observed in serosurveys undertaken 30 years earlier, indicating that the level of endemic St. Louis encephalitis transmission in the city had not changed appreciably in that interval.