Neuraminidase activity in bacterial meningitis.

The relation of neuraminidase to morbidity and mortality was examined in patients with Haemophilus influenzae, meningococcal, and pneumococcal meningitis. Ten strains of H. influenzae and eight strains of meningococci from infected cerebrospinal fluid (CSF) did not elaborate neuraminidase. Each of 27 strains of pneumococci from infected CSF elaborated both neuraminidase and N-acetylneuraminic acid (NANA) aldolase. There was no correlation between amount of neuraminidase secreted in vitro and survival of patients. Values for free and total NANA concentrations were derived from admission CSF samples of 63 patients with meningitis; 18 patients infected with Neisseria meningitidis, 10 with H. influenzae and 35 with Diplococcus pneumoniae. Mean values for total NANA were elevated in each type of bacterial meningitis; however, abnormal concentrations of free CSF NANA were detected only in 17 patients with pneumococcal meningitis. 11 of 18 patients with pneumococcal meningitis showing normal free CSF NANA concentrations were cured, whereas only 4 patients with abnormal free NANA levels survived without residua. Both coma and bacteremia occurred significantly more often among patients with elevated concentrations of free CSF NANA. The association of elevated concentrations of free CSF NANA with coma and with an adverse prognosis suggested that neuraminidase may be a factor in the pathogenesis of penumococcal meningitis.

Detection of human growth hormone receptors on IM-9 cells and peripheral blood mononuclear cell subsets by flow cytometry: correlation with growth hormone-binding protein levels.

We have developed a method using flow cytometry to identify fluorescein-conjugated GH receptors (GHR) on IM-9 lymphocytes and circulating peripheral blood mononuclear cell subsets. Binding to IM-9 cells and peripheral blood mononuclear cells was concentration dependent and could be competitively blocked by the addition of unlabeled human GH, but not by the addition of rat or bovine GH or human insulin or PRL. Using two-color flow cytometric analysis, fluorescein-conjugated human GHR were readily detected on more than 90% of B lymphocytes and monocytes, but only variably on T lymphocytes. B Lymphocytes and monocytes had approximately 6000 GHR/cell. Using two-color flow cytometry, we identified GHR on circulating B lymphocytes in subjects with GH deficiency (n = 9), precocious puberty (n = 6), and Turner syndrome (n = 5) and in seven subjects with miscellaneous disorders, including familial short stature, bone dysplasia, Crohn disease, congenital adrenal hyperplasia, and acromegaly. The percentage of B lymphocytes expressing GHR in subjects with GH deficiency (mean +/- SD, 95 +/- 9%), precocious puberty (91 +/- 15%), and Turner syndrome (84 +/- 15%) was not different from that in normal volunteers (90 +/- 12%; n = 14). In 10 subjects, serum GH-binding protein levels were assayed simultaneously with B lymphocyte GHR. GH-binding protein was normal in all (mean, 1255 pmol/L; range, 773-1809). There was a good correlation between GHR expression on B lymphocytes and GH-binding protein levels (r = 0.75; P = 0.01). We postulate that GHR found on circulating B lymphocytes may contribute to the pool of receptors identified in serum as GH-binding proteins. Two-color flow cytometry appears to be an effective method for the detection of GHR on circulating peripheral blood mononuclear cell subsets. The evaluation of GHR on circulating B lymphocytes may prove to be a useful means of evaluating GH-GHR interactions in subjects with growth disorders.

Organizational models of medical school relationships to the clinical enterprise.

The authors analyzed existing relationships between medical schools and clinical enterprises in order to develop models of these relationships. The conceptual framework for the models uses three variables to assess the nature of the relationships: (1) high academic control-high clinical enterprise control; (2) high academic influence-low academic influence; and (3) self-contained system-open system (i.e., the extent to which the resources needed for clinical education are provided by the relationship between the clinical enterprise and the medical school). The authors present four conceptual models of the relationship between the medical school and the clinical enterprise: (1) The "single ownership; owned integrated system" is characterized by a closed clinical delivery system owned or controlled by the academic institution. (2) The "general partner" organization emphasizes an open clinical environment in which the medical school forms alliances with clinical entities, and the school is a dominant partner. (3) The "limited partner" organization operates with an open clinical delivery system that the school relates to through affiliations and contractual relationships, and the school is a less dominant partner. (4) The "wholly owned, subsidiary" organization operates in a controlled clinical environment in which the medical school is a subsidiary of the larger integrated delivery system. Each model is presented in its pure organizational form, then augmented with descriptions of the different ways that the medical school and other components may relate to each other. Also, the advantages and disadvantages of each model for the medical school are discussed. The authors emphasize that no model is superior to the others; instead, the best choice for a medical school depends on the history, local circumstances, and leadership of the school and other organizations. The authors' intent is to assist the leaders of medical schools as they design strategies for the future relationships of their institutions.

Tapping the power of information: an orientation for academic medical centers.

In September 1994 the Association of American Medical Colleges' (AAMC's) Advisory Panel on the Mission and Organization of Medical Schools (APMOMS) established a working group to address both the long-term and the immediate implications of the expanding capacity of and need for information technology (IT) within academic medical centers (i.e., medical schools and teaching hospitals). Over a two-year period, group members assessed the utilization of IT through surveys of current practices and interactions with acknowledge leaders in the field. They also had discussions with deans and other institutional leaders. The group developed the consensus that proper use of currently available IT is crucial to virtually every aspect of academic medicine's clinical, educational, and research missions. Moreover, current IT technology will be further enhanced by the powerful new applications that are nearing deployment. All group members agreed that IT must become a core competency of academic and medical centers (AMCs), the profession, and individual physicians and scientists to ensure the survival of AMCs in the current highly competitive environments. The authors outline their arguments for the development of strong information systems within AMCs and present basic characteristics of systems that show promise for successful implementation. The y review some of the major institutional obstacles that have hindered the planing and implementation of IT. They conclude with a list of practical institution strategies for success in planning and implementing IT systems, and suggestions for how the AAMC can help members achieve success in these activities.

Fulfilling the social contract between medical schools and the public.

To gain a better understanding of the effects of medical schools related to transformations in medical practice, science, and public expectations, the Association of American Medical Colleges (AAMC) established the Advisory Panel on the Mission and Organization of Medical Schools (APMOMS) in 1994. Recognizing the privileges academic medicine enjoys as well as the power of and the strain on its special relationship with the American public, APMOMS formed the Working Group on Fulfilling the Social Contract. That group focused on the question: What are the roles and responsibilities involved in the social contract between medical schools and various interested communities and constituencies? This article reports the working group's findings. The group describes the historical and philosophical reasons supporting the concept of a social contract and asserts that medical schools have individual and collective social contracts with various subsets of the public, referred to as "stakeholders." Obligations derive implicitly from the generous public funding and other benefits medical school receive. Schools' primary obligation is to improve the nation's health. This obligation is carried out most directly by educating the next generation of physicians and biomedical scientists in a manner that instills appropriate professional attitudes, values, and skills. Group members identified 27 core stakeholders (e.g., government, patients, local residents, etc.) and outlined the expectations those stakeholders have of medical schools and the expectations medical schools have of those stakeholders. The group conducted a survey to test how leaders at medical schools responded to the notion of a social contract, to gather data on school leaders' perceptions of what groups they considered their schools' most important stakeholders, and to determine how likely it was that the schools' and the stakeholders expectations of each other were being met. Responses from 69 deans suggested that the survey provoked thinking about the broad issue of the social contract and stakeholders. Leaders on the same campuses disagreed about what groups were the most important stakeholders. Similarly, the responses revealed a lack of national consensus about the most important stakeholders, although certain groups were consistently included in the responses. The group concludes that medical school leaders should examine their assumptions and perspectives about their institutions' stakeholders and consider the interests of the stakeholders in activities such as strategic planning, policymaking, and program development.

How medical schools can maintain quality while adapting to resource constraints.

To gain a better understanding of the effects on medical schools of ongoing transformations in medical practice, science, and public expectations, the Association of American Medical Colleges (AAMC) formed the Advisory Panel on the Mission and Organization of Medical Schools (APMOMS) in 1994. Six working groups were appointed to address different issues of importance. This article is a report of the findings and recommendations of the Working Group on Adapting to Resource Constraints. That group was charged to consider how leaders in academic medicine can respond to the challenges of external forces and the anticipated diminishing of resources, and to focus on medical schools and how they can maintain quality while reengineering to effect needed changes. The group members developed their thinking within four categories: size of the academic enterprise; organizational models and their relationships to the clinical enterprise; faculty tenure and compensation; and partnerships with capital-intensive entities. Three recommendations for action, to which the APMOMS unanimously agreed, were made to the AAMC, which has already acted upon them in ways described in the article. The group also developed a series of "ideas for consideration," which represent a range of the members' perspectives. The working group did not seek (and probably could not have obtained) unanimous agreement on many of the issues that these ideas focus upon. The ideas are presented as a series of resolutions designed to stimulate discussion and foster better-informed planning.

Capturing the promise of science in medical schools.

To gain a better understanding of the effects on medical schools of transformations in medical practice, science, and public expectations, the Association of American Medical Colleges (AAMC) constituted the Advisory Panel on the Mission and Organization of Medical Schools (APMOMS) in 1994. APMOMS created six working groups to address the issues deemed by panel members to be of highest priority. This article is a report of the findings of the Working Group on Capturing the Promise of Medical Research, which addressed questions concerning the direction of research and the integration of scientific developments in medical education and practice. The working group explored a broad panorama of issues, including those related to sustaining the accomplishments, momentum, and progress of medical research. A dominant theme emerged: the central importance of an environment of discovery to the core missions of medical schools. The present article consists of the group's comments and recommendations on the main topic-the promise of biomedical research in relation to medical education-and their comments and recommendations on five other topics that have important relationships to the main topic and to the group's central charge. These are ethics; academia-industry relations; the administrative structure of medical schools; university-medical school relations; and research funding.

Sustaining the development of primary care in academic medicine. Working Group on Sustaining the Development of Academic Primary Care. Association of American Medical Colleges.

This article is the report of the Working Group on Sustaining the Development of Academic Primary Care, one of the six subgroups of the Advisory Panel on the Mission and Organization of Medical Schools (APMOMS) sponsored by the Association of American Medical Colleges (AAMC). To begin, the group draws a distinction between primary care and generalism. Primary care is a core domain of health care and, in the context of emerging integrated systems, will increasingly be a multidisciplinary shared function. Non-subspecialized physicians, or "generalists," are a key element in the provision of primary care, but do not act alone. Core competencies for primary care are central to the education of all physicians. Therefore, irrespective of workforce goals for generalist physicians, primary care should have a strong, central position in the medical school so that graduates can receive a sound general medical education and can be prepared for any specialty and for lifelong learning in an evolving health care system. For primary care to achieve that position, medical schools must integrate primary care into their missions, strategic plans, operation, organization, academic administrative structures, curriculum development, faculty development (both school- and community-based), resource development, alliances with appropriate clinical services networks, financial policy, and evaluation and educational monitoring systems. The group briefly describes the elements of those changes and also proposes ways that the AAMC and medical school leaders could promote the central role of primary care in medical schools.

Preserving medical schools' academic mission in a competitive marketplace.

To gain a better understanding of the effects on medical schools of transformations in medical practice, science, and public expectations, the AAMC in 1994 formed the Advisory Panel on the Mission and Organization of Medical Schools and appointed six working groups to address relevant issues. This article is a report of the findings of the Working Group on Preserving Medical Schools' Academic Mission in a Competitive Marketplace, which was charged with exploring how medical schools could acquire and/or preserve an adequate patient base for teaching, research, and income generation in a competitive marketplace. The other groups' reports will appear in future issues of Academic Medicine. To understand the diversity of approaches that schools have taken to achieve this goal and to preserve their missions, the group interviewed representatives of nine medical schools, selected to represent a cross section of U.S. medical schools. The interviews took place on four occasions between June 1995 and March 1996. The information and comments shared by participants helped the working group gain insight into the fundamental issues it had been charged to address, including those of new delivery structures, what value schools offer to delivery structures, how education and research can be incorporated and supported financially, possible new pressures on relationships between medical schools and teaching hospitals, changes in faculty physicians' employment relationships and terms, and the role of the medical school in graduate medical education. In collecting and analyzing the data, the working group focused on the distinction between protecting an institution's existing enterprise and preserving an institution's core mission. This article gives a detailed overview of the information and comments each school presented, organized under the appropriate question. The working group's conclusions and commentaries on the findings follow. An appendix presents more detailed summaries of the schools' presentations, organised as case studies. The picture that emerges is complex. The working group concluded that medical schools will take a variety of approaches to define and preserve their missions. Most, but not all, medical schools will be able to secure the patient bases necessary to fulfill their missions even in a competitive marketplace. However, the nature of many of the schools is likely to change, and it is not clear whether the core missions of education and research will continue at their present levels at all schools.

Effects of high ambient temperature on respiration rate, rectal temperature, fetal development and thyrold gland activity in tropical and temperate breeds of sheep.

The effects of high ambient temperatures on rectal temperature (RT), respiration rate (RR), fetal development and serum thyroxine (T(4)) concentrations were stuaied in two experiments involving 35 ewes and 26 lambs from the following ewe groups: 1) Barbados Blackbelly (B), a tropical breed; 2) Dorset (D), a temperate breed; and 3) Blackbelly x Dorset crosses (BxD). Data were obtained on four B, five D and five BxD ewes exhibiting estrus during the summer (Exp. 1). In Exp. 2, eight B, seven D and six BxD ewes were maintained in two environmental chambers (cool, 22.2C; hot, 33.8C) from day 125 of gestation to seven days before the expected lambing date for each breed group (D and BxD, 140+/-1; B, 144+/-1 day of gestation). The B and BxD ewes were more heat-tolerant than D ewes as measured by significantly lower RT and RR in each experiment. Mean lamb birth weight, crown-rump length, number of functional uterine caruncles and caruncle weight and size did not vary significantly among breed groups or temperature chamber (Exp. 2), and there was no indication that the high temperature imposed caused fetal dwarfing in lambs removed from the uterus at a standard age of seven days before expected parturition. Serum T(4) varied markedly among breed groups (P<0.05) in each experiment with B ewes having the lowest and BxD ewes the highest concentration. In Exp. 1, follicular stage T(4) concentrations in B and BxD ewes were lower (P<0.02) than those during the luteal stage of the estrous cycle. The decrease in D ewes was not significant. High ambient temperature (Exp. 2) depressed T(4) levels in D ewes (P<0.05) and also depressed the pituitary-thyroid response to thyrotropin releasing hormone in D lambs. Such was not the case in B and BxD ewes and their lambs.

Effects of rapid weight gain to puberty on reproduction, mammary development and lactation in ewe lambs.

The effects of rapid weight gain to puberty on reproduction, mammary development and milk production in ewes lambing at 13 mo of age were investigated on three trials. A total of 64 Dorset and 93 Suffolk ewe lambs were weaned at 42 d of age and their mean weight was 16 kg. These ewes were assigned, within breed groups, to either a finishing diet or a growing diet. Onset of puberty was determined by daily checks for estrus and ewes were bred beginning at 7 mo of age. In Trial 2, mammary gland development was determined in eight Suffolk ewes from each diet. Ewes on the finishing diet were younger at puberty than those on the growing diet (199 vs 206 d, P<0.05) but required more services per conception (1.3 vs 1.1, P<0.05). Dietary conception rate and lambing rate means were similar. Mean 4-h milk yield was lower (P<0.10) for ewes on the finishing diet (283 g) than for those on the growing diet (310 g). Mammary gland fat pad area was higher (P<0.05) for ewes on the finishing diet compared with those fed for growth. Gross and adjusted duct areas were higher in ewes on the growing diet, but differences were not significant. At puberty, negative correlation coefficients for milk yield with performance traits were as follows: daily weight gain, -0.184 (P<0.08); weight-to-height ratio -0.262 (P<0.01); body condition score, -0.189 (P<0.07); and body weight, -0.212 (P<0.05). Results of this study indicate that rapid weight gain to puberty impairs mammary gland development and milk production in ewe lambs.

Effects of accelerated growth during rearing on reproduction and lactation in ewes lambing at 13 to 15 months of age.

Three trials were conducted using ewe lambs to determine the effects of accelerated growth during rearing on reproduction and lactation. Data were obtained on 113 ewes. Early weaned ewe lambs were randomly assigned to the following prebreeding treatments: (1) thin (T, moderate gain) and (2) fat (F, accelerated gain). They were bred to lamb at 13 to 15 months of age. After breeding, one half of the ewes on the T and F treatments were switched to the other treatment so that postbreeding treatments were TT, TF, FF and FT. Prebreeding treatment did not affect conception rate (T, 95%; F, 96%), but lambing rates were 43, 28 and 27% higher (P<0.05) for F than T ewes in trials 1, 2 and 3, respectively. Daily milk production was higher in T ewes than F ewes for each trial, but the differences were significant only in trial 3. Estimated daily milk yields over the 60-day period were: T ewes, 1482, 1571, 1614 g; F ewes, 1183, 1373, 1321 g for trials 1, 2 and 3, respectively. Number of alveoli also favored T ewes. Switching ewes to the alternate treatment after breeding did not affect reproduction or milk production. Correlations between weight to height ratio and milk yield were negative in trials 1 and 3 but were positive in trial 2. There was no indication that serum T(4) levels affected milk production or reproduction. The results of this study show that accelerated growth during rearing increased lambing rate but may impair milk production. These effects appeared to be fixed by the time the ewes were bred.

Effects of dietary iron on performance and mineral utilization in lambs fed a forage-based diet.

Twenty-four lambs, averaging 29 kg, were used to determine the effect of supplemental dietary Fe on performance and Cu, P, Zn and Mn utilization. Treatments consisted of supplemental Fe at 0, 300, 600 or 1,200 mg/kg diet as ferrous carbonate. The basal diet contained 154 mg Fe/kg diet and consisted of 90% Coastal bermudagrass pellets, 9.45% group corn, .5% sodium chloride and .05% vitamin mix. Lambs were slaughtered after having ad libitum access to diets for 98 to 121 d. Dietary Fe did not affect lamb gain or feed intake. Supplemental Fe increased Fe concentrations in liver (P less than .01), spleen (P less than .01) and bone (P less than .10), but not in kidney and muscle. Serum Fe concentrations and percentage transferrin saturation in serum were increased (P less than .01) by supplemental Fe at 28 and 84 d, but not at the termination of the study. Plasma Cu was decreased (P less than .01) at 56 d, whereas serum ceruloplasmin activity was reduced (P less than .01) at 28 d in lambs fed 1,200 mg Fe/kg diet compared with lambs fed 600 mg Fe/kg diet. Lower levels of Fe (300 and 600) reduced (P less than .01) ceruloplasmin by 56 d and plasma Cu by 84 d compared with controls. Liver Cu also was decreased (P less than .05) by supplemental Fe. Plasma P was decreased slightly (P less than .10) by 28 d and significantly (P less than .01) at the other sampling dates by supplemental Fe.(ABSTRACT TRUNCATED AT 250 WORDS)

Voluntary intake, gain, digestibility, rate of passage and gastrointestinal tract fill in tropical and temperate breeds of sheep.

In trial 1, Coastal bermudagrass pellets were fed for 63 d to 21 growing rams of Barbados Blackbelly (B), Dorset (D) and Blackbelly X Dorset (B X D) breeding to determine the effect of breed on voluntary intake (VI) and total gain. Initially, each breed group consisted of seven rams with mean weights of 18.6, 31.0 and 26.4 kg, respectively. At the end of the intake and growth phase, digestibility, rate of passage and gastrointestinal tract (GIT) fill were determined. Chromium-mordanted fiber was used as a particle phase marker. Intakes during the digestibility-marker phase averaged 75% of the VI determined in the intake and growth phase. Breeds did not differ in VI, total gain or digestibilities of dry matter (DM) and neutral detergent fiber (NDF). Apparent crude protein (CP) digestibility was approximately 3 percentage units higher (P less than .10) for B X D than for B or D rams. Rate of passage was faster (P less than .05) for B X D rams than for the other breed groups, while D rams were intermediate. Total mean retention time (MRT) was shorter (P less than .05) for B X D rams compared with the other breed groups. Ruminal retention time (RRT) was shorter (P less than .05) and GIT fill was less (P less than .10) for D and B X D than for B rams. In trial 2, chopped orchardgrass-alfalfa hay was fed for 26 d to 19 of the same rams used in trial 1. Breed, number of rams and initial weights (kg) were: B, 5, 25.6; D, 7, 39.4; B X D, 7, 35.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Haemonchus contortus resistance in straightbred and crossbred Barbados Blackbelly sheep.

Resistance to Haemonchus contortus infection was studied in two experiments conducted with 52 lambs of widely different genetic background. Breed groups compared were: Dorset (D), Barbados Blackbelly (B), Dorset x Blackbelly (D x B), Suffolk x Blackbelly (S x B), Suffolk x Dorset x Blackbelly (S x D x B,[1/4 B]) and nonBlackbelly (NB, D and S). In each experiment, lambs were raised on concrete from birth and were essentially parasite free until infective larvae were administered. In Exp. 1, D x B, S x D x B and D wether lambs approximately 3 months old were infected with a standard dose of invective larvae estimated to be 98% H. contortus. D x B lambs had a longer (P < .05) prepatency period and, at necropsy 17-day postinfection, had a higher (P < .05) percentage of female parasites classified as immature than did the other breed groups. These data showed that the development of H. contortus larvae was inhibited in D x B host animals. In Exp. 2, B, D x B, S x B and NB ewe and wether lambs approximately 4 months old were treated with three sensitizing doses of H. contortus larvae. These were followed by a challenge infection. On the basis of fecal egg counts (eggs per gram feces, EPG), there was no evidence that the challenge infection induced a self-cure reaction in any breed group. All lambs with B breeding had significantly higher Hb levels at the end of the experiment than did NB lambs. b and S x B lambs had higher (P < .05) Hb levels than the D x B lambs, and B lambs had the highest (P < .05) mean corpuscular hemoglobin concentrations. Five days after the challenge infection, B, D x B and S x B lambs also had significantly higher white blood cell levels than did NB lambs. Significant sex differences were also observed in Exp. 2. Ewe lambs had lower final EPG levels, higher preinfection and postinfection Hb levels and higher maximum postinfection cosinophil levels. Breed x sex interactions for these parameters were not significant.

Relationship between rat heat stress mortality and alterations in reticuloendothelial carbon clearance function.

It has recently been reported that, although bacterial endotoxins of intestinal origin are not associated with death after experimental rat heat stress, a state of endotoxin tolerance significantly decreases the heat stress mortality rate. To determine if this phenomenon were associated with the ability of endotoxins to stimulate clearance by the reticuloendothelial system (RES), the relationship between rat heat stress mortality and carbon clearance by the RES was examined. RES carbon clearance was stimulated by prior treatment with endotoxin, zymosan, or sublethal heat stress, as indicated by the significantly reduced (p less than 0.05) blood carbon concentrations 15 min after carbon injections. Prior treatment with injections of gelatin blocked RES carbon clearance. Rats subjected to endotoxin or sublethal heat treatment were significantly (p less than 0.05) resistant to the experimental heat stress, whereas zymosan treatment had no effect. Blockade of the RES with gelatin significantly (p less than 0.05) increased the heat stress mortality rate. These data compare favorably with previously reported studies evaluating RES function and mortality after experimental injury and shock and indicate that the RES may play a fundamental role in the pathogenesis of, and tolerance to, experimental heat stress.

Development of a new technique for explantation of chronic transvenous pacemaker leads: five initial case studies.

Transvenous removal of chronic pacing leads was attempted using a special locking stylet and dilator sheaths. In five initial cases, three of seven leads were infected; six of seven leads were removed. The stylet was inserted into the conductor lumen and locked into the tip to reinforce and control the lead, permitting retraction without stretching the conductor. Sheaths were advanced over the lead to detach and dilate fibrous encapsulation. In one case, force applied exceeded the locking mechanism's strength; no patient complication resulted. It is concluded that transvenous lead removal is facilitated by a locking stylet and dilation of fibrous tissue with sheaths.