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Prophylactic levels of three ionophorous antibiotics, monensin, salinomycin, and lasalocid, were administered to groups of chickens and turkeys. All three ionophores markedly inhibited invasion of cecal tissues by sporozoites of ionophore-sensitive (IS) Eimeria tenella. Monensin and salinomycin also reduced invasion in turkeys by sporozoites of E. adenoeides, but lasalocid only minimally inhibited invasion. Invasion of ceca of monensin-medicated chickens was significantly greater by sporozoites of ionophore-resistant (IR) E. tenella than of the IS isolate. Concomitant experiments showed significant differences in [14C]monensin accumulation among IS and IR isolates of E. tenella. The decreased uptake of monensin by the IR isolates appeared to be accompanied by a decrease in responsiveness to the activity of monensin as well as to two other ionophores, salinomycin and narasin in cell culture. The amount of monensin, salinomycin or narasin required to inhibit development of E. tenella by 50% was 20 to 40 times higher for the IR isolates than for the IS ones. Collectively, the data suggest that differences in ionophore accumulation by IS and IR isolates of E. tenella might reflect differences in membrane chemistry and that these differences are responsible for the expressions of resistance that were observed in these studies. This expression of resistance appears to be common to all ionophores tested.

In 1968 the University of Washington School of Medicine initiated a new curriculum that included a family physician pathway. Six of these classes have now graduated. Two thirds of the planned strategies for the pathway were actually implemented. Approximately half of the students in each second-year class now choose this pathway. Ninety percent of those graduating have done so in the traditional four years. Seventy-three percent of those in the pathway actually pursued family practice training on graduation. Approximately one third of all University of Washington graduates now enter training for family practice, one third enter internal medicine, 10% enter surgical fields, and 8% enter pediatrics. These rates represent significant increases in the proportion of students entering directly into family practice, internal medicine, and pediatrics training.

An evaluation approach is presented that is designed to deal with the complex educational problems associated with community-based teaching. Such problems include using instructors with limited training in teaching, ensuring comparability of student experiences, monitoring students' performance in dispersed settings, and maintaining adequate communications among involved parties. The approach is based on a careful delineation of information needs and data sources followed by the design and strategic combination of evaluation instruments in order to promote efficiency in data collection. An application of the approach is described for an undergraduate clerkship in family medicine taught at multiple sites at the University of Washington School of Medicine. Nine instruments are described for eliciting information from four sources to satisfy the needs of five groups associated with the course. Sample results are presented suggesting that the approach is effective and may prove useful to others involved with teaching in dispersed settings.

Narasin, apolyether ionophorous antibiotic capable of acting as a transmembrane carrier of cations, has a growth inhibitory effect on Acholeplasma laidlawii, permitting only 20% survival when present as 0.1 micrograms/ml in an undefined growth nutrient or fatty acid-deficient nutrient supplemented only with palmitic acid. When A. laidlawii is propagated in fatty acid-deficient nutrient supplemented with linoleic acid, however, the organisms become 40 times more sensitive to the growth inhibitory effect of this antibiotic. The actual fatty acid composition of the membranes would indicate that a higher degree of unsaturation enhances ionophore activity.

Twenty-six patients were interviewed in five clinics at the Hunan Medical School in the People's Republic of China to assess the degree to which patients presenting with medical problems had primarily underlying psychological and social concerns. Patients in all five clinics (paediatrics, internal medicine, otolaryngology, urology and gynaecology) demonstrated a high degree of non-medical concerns. Fear of cancer was common. Many patients mentioned concerns about their children, sexual problems, or other family problems. Both patients and physicians seemed to be comfortable discussing the patients' personal problems and concerns. A medical presentation of psychosocial concerns was as common in China as it is in the United States.

Increasing attention in the literature has focused on the relationship between psychosocial factors and infertility. This study presents a psychosocial profile of infertile couples over a two-year period. During this period, psychosocial data including life change, social support, and personality traits were obtained prospectively from 134 individuals participating in the In Vitro Fertilization Program of the Jones Institute of Reproductive Medicine at the Eastern Virginia Medical School. Instruments utilized included the Life Experiences Survey, the Family APGAR, the Friends APGAR, the Multidimensional Health Locus of Control, and the Eysenck Personality Inventory. Despite the presumed adverse psychological influence of their infertility, Life Experience Survey scores for both men and women did not differ significantly from normative data. Family APGAR scores indicated a high degree of satisfaction with family function. Friends APGAR scores were somewhat lower than normative data. The Multidimensional Health Locus of Control, a measure of perception regarding factors influencing health outcomes, was unremarkable. The Eysenck Personality Inventory revealed a lower score on the neuroticism scale for the men. These psychosocial results were surprisingly normal.

Obese (ob/ob) and lean mice were adrenalectomized at 3 or 6 wk of age and fed a high-carbohydrate stock diet or a high-fat semipurified diet for 3 wk. Adrenalectomy of obese mice fed the stock diet reduced the energy intake, energy gain, and efficiency of energy retention so that the values equaled those of lean mice. Hindlimb muscle gain of adrenalectomized obese mice fed the stock diet increased by 50-100%, and concentrations of plasma insulin were reduced so that they also approached values in lean mice. In contrast to results obtained when the stock diet was fed, adrenalectomy of obese mice fed the high-fat diet resulted in only slight reductions in energy intake, energy gain, or efficiency of energy retention. Likewise, muscle gain was not improved nor were plasma insulin concentrations decreased when adrenalectomized obese mice were fed the high-fat diet. Although adrenal secretions contribute substantially to the gross obesity that develops in ob/ob mice fed the stock diet, these secretions are unnecessary for development of obesity in ob/ob mice fed the high-fat diet. Factors other than adrenal secretions per se, which are influenced by diet composition, thus mediate development of obesity in ob/ob mice.

The concentration of progesterone in milk fat was measured to ascertain whether knowledge of corpus luteum function could be used to increase reproductive efficiency. As they calved, 47 cows were assigned to either a milk-sampled group (24) or an unsampled control group (23). Progesterone concentrations indicative of a functional corpus luteum were first present at an average of 29.4 days postpartum. The average postpartum interval to first estrus was 49 days for cows sampled and 7.19 days for control cows. The postpartum interval to conception was 84.8 days for sampled cows and 113.7 days for control cows. Twenty of 63 (31.7%) ovulations were not associated with behavioral estrus. Cystic ovarian disease with periods of anestrus were observed in five cows. We conclude that failure to detect estrus was a more limiting factor in reproductive efficiency than was anestrus. To determine the reproductive status after breeding, we measured progesterone concentrations on days 19 through 23 postinsemination. Progesterone was higher for pregnant than for nonpregnant cows on all days. However, only on days 20 and 21 was there complete separation of the progesterone ranges in pregnant and nonpregnant cows.

There is substantial evidence that hyperglycemia does play a role in the development of long-term complications, although a genetic predisposition to these complications seems to be important. Also the literature seems to suggest that the degree of hyperglycemia correlates well with both the severity and incidence of long-term complications. However, looking at recent studies in the attempt to answer the question of "can we prevent or minimize complications," we must conclude that there is no definitive evidence that the typical long-term complications of microvascular or macrovascular disease can be prevented with tight control. Hopefully, the current study under way at the NIH will help clarify this issue. It seems likely after reviewing all the evidence that future studies will show tight control to be beneficial. The clinician must weigh the costs of tight control against the potential benefits, particularly in the type II diabetic. It seems prudent to strive for the best control that can be achieved within the confines of the patient's resources, to pay meticulous attention to all factors contributing to complications, such as hypertension and smoking, and to avoid subjecting the patient to undue risks.

Free Eimeria tenella sporozoites were exposed to the anticoccidial ionophores monensin, lasalocid, narasin, or salinomycin for 4 hr at 40 C, whereupon the drugs were removed by dilution centrifugation and the parasites inoculated into cultures of chick kidney cells. Cultures were fixed and stained at 4 and 96 hr postinoculation to determine the effect of ionophore uptake by the extracellular sporozoites on invasion and development. Pretreatment with each of these antibiotics significantly reduced the number of intracellular sporozoites and dramatically inhibited asexual development. These effects were dose-dependent. Exposure of free (extracellular) sporozoites to monensin at 40 C caused a significant decline in the number of surviving organisms over time as compared to nontreated sporozoites. This response also appeared to be dose-dependent. Scanning and transmission electron microscopy revealed that the surface of the treated sporozoites was very irregular and the organisms often exhibited a gross swelling. These results indicated that free Eimeria tenella sporozoites may incorporate a potentially lethal concentration of the polyether ionophorous antibiotics and that a coccidiocidal activity may be expressed whether or not penetration of host's cells occurs.

A number of benefits have been claimed for early ambulatory experience in the training of family physicians, although few practical examples have been reported. This paper describes an approach to the education of first and second year medical students interested in family medicine which places heavy emphasis on community-based ambulatory care. During the first year, an elective introductory preceptorship permits students to participate in the office practice of a family physician in a limited role. Seminars are offered concurrently to provide integrating principles and perspective. In the second year, a nine-month-long continuity clerkship is offered in which students gain intimate contact with a small panel of families and practice the skills of primary care in the offices of family physicians. Clinical experience is accompanied by weekly seminars and integrated with elements of the required curriculum. Selected evaluation data are presented, which attest to the achievement of course objectives and provide support for the claim that this approach is beneficial to students seeking careers in primary care.

Sporozoites of embryo-adapted lines of Eimeria tenella, E. brunetti and E. necatrix were recovered from monensin medicated chickens. The viability of these sporozoites was compared with that of sporozoites recovered from unmedicated birds by assessing their infectivity in chicken embryos. Sporozoites of the three species of Eimeria recovered from 100 parts/10(6) monensin-medicated birds produced infections in embryos which were 94 to 98% less severe than infections resulting from the inoculation of sporozoites recovered from unmedicated chickens. A concomitant scanning electron microscope study revealed no apparent ultrastructural damage to the exposed sporozoites. Timed medication experiments in chickens showed that medication with monensin for the period covering sporozoite penetration in vivo was almost completely effective, being comparable to continuous medication. Medication started before infection (to ensure tissue concentrations of monensin) but terminating 5 to 7 hours before the oocysts were inoculated was ineffective.

The health sciences literature indicates that although continuity often has been shown to be associated with a number of favorable outcomes, the concept is as yet poorly conceptualized and difficult to quantify. In this paper the authors describe an approach to teaching continuity developed at the University of Washington. Beginning in 1973--74 second-year students in an elective family medicine preceptorship were placed with practicing family physicians one-half day per week for a complete academic year. The medical care of a few families was closely followed by each student throughout the period. Required written reports of each student's longitudinal-care experiences were analyzed to identify student-perceived benefits of extended patient contact. Three-fourths of the students over a two-year period were judged to have experienced important aspects of continuity. Results suggest that the teaching program described is a viable means for teaching students to recognize, appreciate, and employ approaches to patient care available only in settings characterized by continuity.

This study investigated the effects of visual and auditory modality preferences on work recall in bisensory and unisensory split-span tasks. Subjects tended to perform better in the bisensory rather than unisensory condition. Modality preferences (n = 72 subjects) were generally unrelated to performance in these experimental conditions. These findings suggest that preferences for a modality are better characterized as response biases rather than as increased processing capacity for preferred modality material.

Eimeria tenella sporozoites were incubated in the presence of 3 different [14C]-labeled sugars; D-glucose, 2-deoxy-D-glucose and 3-O-methyl-D-glucose. The initial velocity, Vi, of uptake of D-glucose and 2-deoxy-D-glucose was similar, 41 micrograms/10(10) sporozoites/min and 46 micrograms/10(10) sporozoites/min, respectively; whereas that for 3-O-methyl-D-glucose was significantly lower, 17 micrograms/10(10) sporozoites/min. Initial velocity studies also revealed that glucose uptake was a saturable event, with an apparent KT of 20 mM and an apparent Vmax of 312 micrograms/10(10) sporozoites/min. Uptake was unaffected by exogenous sodium levels or the presence of ouabain. However, 0.1 mM phloretin significantly inhibited glucose uptake. Thus, it would appear that E. tenella sporozoites possess a Na-independent, phloretin-sensitive, carrier-mediated monosaccharide-transport system.

Forty-two lambs were derived by hysterectomy from 27 ewes. Eight ewes had lesions of chronic progressive pneumonia (CPP) and 19 did not. Eleven lambs were derived from ewes with lesions of CPP. These 11 lambs were maintained in isolators under germfree conditions until killed at 2 to 4 months of age. Lungs from each lamb were examined for gross and microscopic lesions of CPP and examined by microbiological cultural technique (blood, eosin methylene blue, and PPLO agar). The lungs of one 4-month-old lamb from a ewe infected with CPP had foci of gray consolidation in the apical and cardiac lobes. The microscopic changes were comparable to those in the dam. The lungs of a 2.5-month-old lamb from a ewe infected with CPP had lymphocytic accumulations in the alveolar walls and around blood vessels and bronchioles. The 9 other lambs were free of lesions. Neither bacteria nor mycoplasmas were isolated from any of the 11 lambs. Lesions of CPP were not found in 31 lambs from the 19 noninfected ewes.

We reviewed our management of children with vesicoureteral reflux and ureteropelvic junction obstruction in the same renal unit. Of the children who underwent pyeloplasty for ureteropelvic junction obstruction 9 per cent also had vesicoureteral reflux. These children were almost exclusively boys. Ureteropelvic junction obstruction was caused mostly by a stricture or fixed kinks of the upper ureter. Vesicoureteral reflux was primarily grade IV and was associated with abnormal morphology of the ureteral orifice. Pyeloplasty was the initial surgical correction and ureteral reimplantation was performed expectantly.

This study examines the relationship between selected interview characteristics, particularly physicians' verbal behaviors, and levels of patient satisfaction and understanding. Twenty-nine initial patient interviews by 11 physicians at the University of Washington Hospital Family Medical Center were videotaped and rated using a modified Bales' technique. Questionnaires provided measures of patient satisfaction and understanding. Results of correlation analysis indicate that higher patient satisfaction was associated with greater interview length, increases in the proportional time spent by the physician in presenting information and discussing prevention, and shorter chart review times. Increased patient understanding was associated with increases in the proportional time spent presenting both information and opinions, close physical proximity, and reduced chart review time. Implications of the results are discussed as well as methodological issues relating to further research.

Extracellular Eimeria tenella sporozoites exposed to 1.0 microgram/ml monensin at 40 C had an accelerated rate of sodium influx as well as an increased rubidium uptake that was inhibited by the cardiac glycoside, ouabain. These results suggested the presence of a functional (Na+-K+)-ATPase and its stimulation by monensin. Under the same conditions, sporozoite ATP concentrations declined, lactate production increased and the rate of amylopectin utilization was enhanced. Exposure to monensin also appeared to stimulate the rate of sporozoite glycolysis. The results of this study demonstrated that the cidal effect of monensin on extracellular sporozoites was caused by the capability of the ionophore to act as a transmembrane sodium carrier.

The relationship of life change to the onset of cancer was studied in 22 pairs of HLA-identical siblings who were discordant for hematologic malignancies. The twin pairs were hospitalized for bone marrow transplantation. Life change was measured using a well-validated instrument, the Schedule of Recent Experiences (SRE). Contrary to our expectations, we were unable to document increased life changes in the sick twins. The timing of administration of the SRE with respect to the transplant did influence reporting of life events. However, regardless of timing of administration, in the period antedating the diagnosis of malignancy the healthy donor twins had increased or equivalent life changes when compared to their sick twins.

The questions of illness susceptibility and the how and why of the onset of illness are of great concern to family physicians, who are constantly presented with a bewildering array of maladies. This paper presents a model of illness onset as related to life change which is felt to be a highly relevant and useful concept for family physicians. This model has been developed over many years and proposes that illness onset is predictably related to life change, which in turn is a reflection of the amount of coping required. The specific development of these concepts is presented in detail including the development and quantitation of the social readjustment rating scale which quantifies life changes.

A ten-year experience with a continuity clerkship taught to second-year medical students is described. Students enrolled in this course spend one half-day per week for nine months with a practicing family physician, attend a weekly seminar or workshop, and write a longitudinal patient care report. This comprehensive report summarizes their experience with a patient or a family and addresses pertinent medical and psychosocial issues. Forty-four of these reports were analyzed for the 1981-82 academic year. The analysis revealed that the main benefits to the students from the longitudinal experience were (1) recognizing the importance of continuity of care, (2) observing the interplay between the social environment, family, and the patient's health, (3) gaining insight into the role of the family physician, and (4) experiencing the difficulties of chronic disease management.

This study demonstrates that there is a definite constancy to nonverbal behavioral interaction between patient and physician in a defined office interview setting. This work also introduces the technique of lag sequential analysis into family medicine research. Further refinements of study design and technique are needed in future studies to elucidate information that would be helpful to physicians in the management and care of patients and in patient education.

The interview portion of 34 patient-physician visits at a family medical center was videotaped. Videotapes were screened by two judges in two major nonverbal categories, immediacy and relaxation. Physician and patient were scored separately at 40-second intervals for 11 component parameters of the two major categories. These scores were correlated with patient satisfaction and understanding, ascertained by post-interview questionnaire. For analytical purposes, patients were assigned to low or high satisfaction groups and low or high understanding groups. Statistically significant (P less than or equal to 05) differences between low and high satisfaction groups were demonstrated with respect to overall physician immediacy; five individual physician nonverbal parameters; and two individual patient nonverbal parameters. Similar statistical results were obtained for understanding groups. This preliminary investigation suggests that nonverbal behavior of the physician in the patient-physician interview is important in determining patient satisfaction and understanding.

We examined how prey size-distributions influence size-specific foraing rate and food gain, i.e., food intake scaled to metabolic demands, in Jefferson's and small-mouth salamander larvae. Ambystoma jeffersonianum larvae sampled on 17 dates from a farm pond whose fauna was dominated by macrozooplankton and chironomid larvae were rarely gape-limited, and total volume of food in the stomach (VS) showed only a slight tendency to increase with larval size. Although 15 of 17 correlation coefficients of VS with larval size were positive, only 1 of 17 correlations were statistically significant, and body size explained only 8% of the overall variation in VS. Correlation coefficients of food gain and body size were positive in 9 cases and negative in 8, but only 3 were statistically significant.In contrast, Ambystoma texanum larvae in 42 samples taken from five sites dominated by macrozooplankton as well as relatively large isopods and amphipods were almost always gape-limited, and VS tended to increase markedly with larval size. 40 of 42 correlation coefficients of VS and larval size were positive, and 19 correlations were statistically significant. Body size in turn explained about 35% of the overall variation in VS. Correlation coefficients of food gain and larval size were positive in 32 of 42 samples, and 9 of 10 significant correlations were positive.When food is limiting and prey selection is not limited by gape, smaller larvae may grow as fast or in some cases faster than larger larvae because they are nearly as effective foragers, but have lower metabolic demands. Larger larvae may in turn grow faster than smaller larvae in environments which support a broad size spectrum of prey, particularly when gape limitations are highly disproportionate among size classes. The growth rate of larvae in one size class relative to another depends primarily on the extent to which increased foraging rate compensates for higher energy demands as body size increases. Size-specific foraging rate may in turn be strongly influenced by the prey size-distribution within a habitat. These relationships suggest that relative size is not always a good a priori predictor of exploitative competitive ability.

The methylation of histidine in actin from various muscle and nonmuscle sources has been studied by formation of phenylthiocarbamyl derivatives and subsequent reverse-phase high-pressure liquid chromatographic separation and analysis of actin hydrolyzates. All the actin species examined were found to contain 3-methylhistidine. This method has also been used in assays for the enzyme(s) responsible for methylation of rabbit skeletal muscle actin and to investigate the formation of other methylated residues in vitro. 3-Methyl-histidine is the major methylation product in this in vitro reaction.

Naturally occurring Trypanosoma theileri infection was studied in two cattle herds. Herd A was a dairy herd of approximately 250. Herd B was an isolated herd of 32 and contained both dairy and beef breeds. Blood samples were collected from all animals in Herd A during July and August on two successive years. Samples were collected from Herd B at monthly intervals. Total leukocyte and differential counts packed cell volume determinations, and trypanosome cultures were made on each sample. Infection was detected in all age groups between seven months and fifteen years but it was rare in calves. Infected animals were not consistently positive for trypanosomes on consecutive blood cultures and there was considerable variation between infected individuals. Positive cultures were usually obtained from some animals while others were positive intermittently. No correlation was found between trypanosome isolations and the season of the year.A correlation was found between trypanosome isolation and lymphocytosis. Of the 920 blood samples examined, approximately one in every five trypanosome positive samples had lymphocyte levels in the Bendixen positive range. Approximately one in every twenty trypanosome negative samples had lymphocyte numbers in the Bendixen positive range. Evidence indicated that trypanosome isolation from animals with lymphocytosis was not caused by increased numbers of infected buffy coat cells in the inoculum cultured. Eight calves were inoculated intravenously with trypanosome-infected blood. Lymphocyte numbers increased an average of 3549 per cumm above pre-inoculation levels in seven and remained essentially unchanged in one. Prior to inoculation with infective blood, two of the calves were intravenously inoculated with trypanosome-infected blood that had been frozen and thawed to kill the trypanosomes contained in it. Neither developed lymphocytosis following this inoculation. No clinical disease problems which could be attributed to trypanosome infection were found.