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PubMed2001

SSM Health Care clinical collaboratives: improving the value of patient care in a health care system.

BACKGROUND: In 1998 SSM Health Care (St Louis) began a series of clinical collaboratives modeled after The Institute of Healthcare Improvement (Boston) Breakthrough Series. There are now four collaboratives, with 46 teams in progress, and four additional collaboratives are scheduled. COLLABORATIVE TOPICS AND STRUCTURE: Each collaborative consists of three phases: the prework, active, and the continuous improvement phases. The structure of the collaboratives is quite similar to that of the Institute for Healthcare Improvement Breakthrough Series. However, the SSMHC collaboratives include a continuous improvement phase, which was designed to help maintain gains from the projects and to involve entities not originally involved in the collaborative. RESULTS OF COLLABORATIVES IN PROGRESS: Entity teams participating in multiple collaboratives seem to ascend a learning curve and become progressively more skilled in subsequent collaborative work. In Collaborative 1--Improving the Secondary Prevention of Ischemic Heart Disease--the participating entities showed significant improvement in cholesterol screening and treatment. In Collaborative 2--Improving Prescribing Practices--the collaborative teams also showed significant improvement, with a combined cost savings of approximately $450,000 per year. Collaboratives 3--Using Patient Information to Improve Care and Assure Success-and-4--Enhancing Patient Safety Through Safe Systems--are under way. SUMMARY: The collaboratives accelerate improvement work through sharing of successes and failures and peer influence within a reinforcing environment. Most of the collaborative teams have reached their project goals, and the pace of clinical improvement work has accelerated since the start of the collaboratives. The collaboratives provide an environment for clinicians to constructively participate in improvement of patient care.

Cooperative Behavior↗
PubMed2002

Enhancing the parenting skills of Head Start families during the transition to kindergarten.

Head Start centers provide an excellent context for the implementation and success of family-based interventions, particularly home visiting. Based on a developmental-ecological model, a universal family-centered intervention was implemented with Head Start families. Outcome data from this parenting and home visiting program is presented (Project STAR: Steps to Achieving Resilience). Results suggest that both parenting groups and home visiting interventions are effective at enhancing parenting skills: however, home visiting programs have a higher participation rate. Additionally, home visiting by familiar staff was particularly successful at improving parenting skills at follow-up. Results suggest that embedding targeted interventions in universal strategies can be an effective means of engaging families in services. The results have implications for service delivery methods in early childhood as a means of enhancing parent participation.

Child↗
PubMedDate not supplied

Clarification of the database concept.

Our concern is that nursing databases be structured to improve the efficiency of decision-making in nursing. The selection of database management systems that are compatible with the computer resources in a majority of settings is important to methodology. To facilitate methodological development, we encourage the inclusion of information in the nursing literature that details the investments in personnel, equipment, and facilities required to develop computerized databases. In the current state of affairs, determining the personnel and budgets for the development, update, and maintenance of computerized databases and related data management systems is somewhat like trying to pin the tail on the donkey while blindfolded. However some of the frustrations encountered at the start of new endeavors can be lessened if we share our experiences in project management as we report findings from our work.

Computers↗
PubMedDate not supplied

Applications of time-varying gradients in existing magnetic resonance imaging systems.

This paper describes several applications of magnetic resonance imaging (MRI) with time-varying gradients within the framework of existing imaging systems. An alternative form of slice selection is shown where a time-varying gradient is used, during the reception interval, to isolate the slice of interest (the reconstruction of the slice itself is treated by the conventional techniques). This system allows for precise control of the slice, thinner slices (less than 1 mm) and the ability to select multiple, closely packed slices using a single imaging sequence. All this is done by postprocessing so the slice(s) of interest can be selected after the measurements have been completed. It is also shown how time-varying gradients can be used to generate the signals required for conventional projection-reconstruction and two-dimensional Fourier transform techniques (yet achieving higher resolution and using a resonant gradient system). In addition to cross-sectional imaging, this same approach provides a simple system for projection imaging of the entire volume. All of these techniques constitute a good starting point for the exploitation of time-varying gradients for fast, high-resolution MRI with existing imaging systems.

Filtration↗
PubMed1976

Effect of polymyxin on the ultrastructure of the outer membrane of wild-type and polymyxin-resistant strain of Salmonella.

The effect of polymyxin on two sets of Salmonella mutants was studied by thin-section and scanning electron microscopy. Polymyxin (in increasing concentrations, starting just below bactericidal effect) caused the appearance of the previously described rodlike projections on the cell surface of wild-type (smooth, polymyxin-sensitive) bacteria. These projections seemed to involve the outer membrane of the cell wall. In rough mutants, which are deficient in lipopolysaccharide, the projections were much smaller and flat. Higher concentrations of polymyxin were required to produce morphological effects in polyxmin-resistant mutants of both smooth and rough forms. Furthermore, in these mutants polymyxin caused vesicle-like bulging of the total outer membrane quite different in appearance from the rodlike projections of the wild type.

Cell Membrane↗
PubMed1999

Escherichia coli mutants lacking all possible combinations of eight penicillin binding proteins: viability, characteristics, and implications for peptidoglycan synthesis.

The penicillin binding proteins (PBPs) synthesize and remodel peptidoglycan, the structural component of the bacterial cell wall. Much is known about the biochemistry of these proteins, but little is known about their biological roles. To better understand the contributions these proteins make to the physiology of Escherichia coli, we constructed 192 mutants from which eight PBP genes were deleted in every possible combination. The genes encoding PBPs 1a, 1b, 4, 5, 6, and 7, AmpC, and AmpH were cloned, and from each gene an internal coding sequence was removed and replaced with a kanamycin resistance cassette flanked by two res sites from plasmid RP4. Deletion of individual genes was accomplished by transferring each interrupted gene onto the chromosome of E. coli via lambda phage transduction and selecting for kanamycin-resistant recombinants. Afterwards, the kanamycin resistance cassette was removed from each mutant strain by supplying ParA resolvase in trans, yielding a strain in which a long segment of the original PBP gene was deleted and replaced by an 8-bp res site. These kanamycin-sensitive mutants were used as recipients in further rounds of replacement mutagenesis, resulting in a set of strains lacking from one to seven PBPs. In addition, the dacD gene was deleted from two septuple mutants, creating strains lacking eight genes. The only deletion combinations not produced were those lacking both PBPs 1a and 1b because such a combination is lethal. Surprisingly, all other deletion mutants were viable even though, at the extreme, 8 of the 12 known PBPs had been eliminated. Furthermore, when both PBPs 2 and 3 were inactivated by the beta-lactams mecillinam and aztreonam, respectively, several mutants did not lyse but continued to grow as enlarged spheres, so that one mutant synthesized osmotically resistant peptidoglycan when only 2 of 12 PBPs (PBPs 1b and 1c) remained active. These results have important implications for current models of peptidoglycan biosynthesis, for understanding the evolution of the bacterial sacculus, and for interpreting results derived by mutating unknown open reading frames in genome projects. In addition, members of the set of PBP mutants will provide excellent starting points for answering fundamental questions about other aspects of cell wall metabolism.

Bacterial Proteins↗
PubMed2002

Apollo: a sequence annotation editor.

The well-established inaccuracy of purely computational methods for annotating genome sequences necessitates an interactive tool to allow biological experts to refine these approximations by viewing and independently evaluating the data supporting each annotation. Apollo was developed to meet this need, enabling curators to inspect genome annotations closely and edit them. FlyBase biologists successfully used Apollo to annotate the Drosophila melanogaster genome and it is increasingly being used as a starting point for the development of customized annotation editing tools for other genome projects.

Animals↗
PubMed1999

Cost-effectiveness of respiratory syncytial virus prophylaxis among preterm infants.

OBJECTIVES: To evaluate the costs and benefits of two new agents, respiratory syncytial virus immune globulin (RSVIG) and palivizumab, to prevent respiratory syncytial virus (RSV) infection among premature infants discharged from the neonatal intensive care unit (NICU) before the start of the RSV season. Method. Decision analysis was used to compare the projected societal cost-effectiveness of three strategies-RSVIG, palivizumab, and no prophylaxis-among a hypothetical cohort of premature infants. Probabilities and costs of hospitalization were derived from a cohort of 1721 premature infants discharged from six Kaiser Permanente-Northern California NICUs. Efficacies of prophylaxis were based on published trials. Costs of prophylaxis were derived from published sources. Mortality among infants hospitalized for RSV was assumed to be 1.2%. Future benefits were discounted at 3%. RESULTS: Palivizumab was both more effective and less costly than RSVIG. Cost-effectiveness varied widely by subgroup. Palivizumab appeared most cost-effective for infants whose gestational age was </=32 weeks, who required >/=28 days of oxygen in the NICU, and who were discharged from the NICU from September through November. In this subgroup, palivizumab was predicted to cost $12,000 per hospitalization averted (after taking into account savings from prevention of RSV admissions) or $33,000 per life-year saved, and the number needed to treat to avoid one hospitalization was estimated at 7.4. However, for all other subgroups, ratios ranged from $39,000 to $420,000 per hospitalization averted or $110,000 to $1,200,000 per life-year saved, and the number needed to treat extended from 15 to 152. The results were sensitive to varying assumptions about the cost and efficacy of prophylaxis, as well as the probability of hospitalization, but were less sensitive to the cost of hospitalization. CONCLUSION: In our model, the cost of prophylaxis against RSV for most subgroups of preterm infants was high relative to the benefits realized. Lower costs might permit the benefits of prophylaxis to be extended to additional groups of preterm infants.

Antibodies, Monoclonal↗
PubMed2001

Development of the lymphatic network in the muscle coat of the rat jejunum as revealed by enzyme-histochemistry.

The process of lymphangiogenesis was studied in the muscle coat of the rat small intestine by light and scanning and transmission electron microscopy; identification of lymphatic vessels was made by 5'-nucleotidase staining. Light and scanning electron microscopy demonstrated that the intramuscular lymphatic network formation, which started only postnatally, was attributable to the vascular sprouting of slender lymphatic endothelial projections and to a splitting of the vessels, causing intervascular meshes of various sizes. The growing lymphatics were consistently closed by the endothelial cells, which were characterized by an abundance of cell organelles and prominent cytoplasmic processes. The cells often revealed close contacts with the processes of developing smooth muscle cells in the jejunal muscle coat, suggesting a possible role for the latter cells in the guidance of the lymphatic extension. The present study is the first to suggest the closed nature of lymphatics persisting throughout their development, even at the initial stage of lymphangiogenesis.

5'-Nucleotidase↗
PubMed2000

[Microbial diversity of deep-sea extremophiles--Piezophiles, Hyperthermophiles, and subsurface microorganisms].

Knowledge of our Planet's biosphere has increased tremendously during the last 10 to 20 years. In the field of Microbiology in particular, scientists have discovered novel "extremophiles", microorganisms capable of living in extreme environments such as highly acidic or alkaline conditions, at high salt concentration, with no oxygen, extreme temperatures (as low as -20 degrees C and as high as 300 degrees C), at high concentrations of heavy metals and in high pressure environments such as the deep-sea. It is apparent that microorganisms can exist in any extreme environment of the Earth, yet already scientists have started to look for life on other planets; the so-called "Exobiology" project. But as yet we have little knowledge of the deep-sea and subsurface biosphere of our own planet. We believe that we should elucidate the Biodiversity of Earth more thoroughly before exploring life on other planets, and these attempts would provide deeper insight into clarifying the existence of extraterrestrial life. We focused on two deep-sea extremophiles in this article; one is "Piezophiles", and another is "Hyperthermophiles". Piezophiles are typical microorganisms adapted to high-pressure and cold temperature environments, and located in deep-sea bottom. Otherwise, hyperthermophiles are living in high temperature environment, and located at around the hydrothermal vent systems in deep-sea. They are not typical deep-sea microorganisms, but they can grow well at high-pressure condition, just like piezophiles. Deming and Baross mentioned that most of the hyperthermophilic archaea isolated from deep-sea hydrothermal vents are able to grow under conditions of high temperature and pressure, and in most cases their optimal pressure for growth was greater than the environmental pressure they were isolated from. It is possible that originally their native environment may have been deeper than the sea floor and that there had to be a deeper biosphere. This implication suggests that the deep-sea hydrothermal vents are the windows to a deep subsurface biosphere. A vast array of chemoautotrophic deep-sea animal communities have been found to exist in cold seep environments, and most of these animals are common with those found in hydrothermal vent environments. Thus, it is possible to consider that the cold seeps are also one of slit windows to a deep subsurface biosphere. We conclude that the deep-sea extremophiles are very closely related into the unseen majority in subsurface biosphere, and the subsurface biosphere probably concerns to consider the "exobiology".

Archaea↗
PubMed2005

Fever and hypothermia in systemic inflammation: recent discoveries and revisions.

Systemic inflammation is accompanied by changes in body temperature, either fever or hypothermia. Over the past decade, the rat and mouse have become the predominant animal models, and new species-specific tools (recombinant antibodies and other proteins) and genetic manipulations have been applied to study fever and hypothermia. Remarkable progress has been achieved. It has been established that the same inflammatory agent can induce either fever or hypothermia, depending on several factors. It has also been established that experimental fevers are generally polyphasic, and that different mechanisms underlie different febrile phases. Signaling mechanisms of the most common pyrogen used, bacterial lipopolysaccharide (LPS), have been found to involve the Toll-like receptor 4. The roles of cytokines (such as interleukins-1beta and 6 and tumor necrosis factor-alpha) have been further detailed, and new early mediators (e.g., complement factor 5a and platelet-activating factor) have been proposed. Our understanding of how peripheral inflammatory messengers cross the blood-brain barrier (BBB) has changed. The view that the organum vasculosum of the lamina terminalis is the major port of entry for pyrogenic cytokines has lost its dominant position. The vagal theory has emerged and then fallen. Consensus has been reached that the BBB is not a divider preventing signal transduction, but rather the transducer itself. In the endothelial and perivascular cells of the BBB, upstream signaling molecules (e.g., pro-inflammatory cytokines) are switched to a downstream mediator, prostaglandin (PG) E2. An indispensable role of PGE2 in the febrile response to LPS has been demonstrated in studies with targeted disruption of genes encoding either PGE2-synthesizing enzymes or PGE2 receptors. The PGE2-synthesizing enzymes include numerous phospholipases (PL) A2, cyclooxygenases (COX)-1 and 2, and several newly discovered terminal PGE synthases (PGES). It has been realized that the "physiological," low-scale production of PGE2 and the accelerated synthesis of PGE2 in inflammation are catalyzed by different sets of these enzymes. The "inflammatory" set includes several isoforms of PLA2 and inducible isoforms of COX (COX-2) and microsomal (m) PGES (mPGES-1). The PGE2 receptors are multiple; one of them, EP3 is likely to be a primary "fever receptor." The effector pathways of fever start from EP3-bearing preoptic neurons. These neurons have been found to project to the raphe pallidus, where premotor sympathetic neurons driving thermogenesis in the brown fat and skin vaso-constriction are located. The rapid progress in our understanding of how thermoeffectors are controlled has revealed the inadequacy of set point-based definitions of thermoregulatory responses. New definitions (offered in this review) are based on the idea of balance of active and passive processes and use the term balance point. Inflammatory signaling and thermoeffector pathways involved in fever and hypothermia are modulated by neuropeptides and peptide hormones. Roles for several "new" peptides (e.g., leptin and orexins) have been proposed. Roles for several "old" peptides (e.g., arginine vasopressin, angiotensin II, and cholecystokinin) have been detailed or revised. New pharmacological tools to treat fevers (i.e., selective inhibitors of COX-2) have been rapidly introduced into clinical practice, but have not become magic bullets and appeared to have severe side effects. Several new targets for antipyretic therapy, including mPGES-1, have been identified.

Animals↗
PubMedDate not supplied

Delegation can make (or break) your career.

Delegation is not a soft skill. Physician executives who do not delegate well and strategically cannot expect to achieve the top jobs now or in the future. It's not enough to have great communications skills to convey your vision. You won't achieve that vision alone; you must have a great team to bring that vision to fruition. However, you can't delegate your first and most important step--self-assessment. To maximize your strengths and minimize your weaknesses, you'll need a clear view of what makes you tick. Then start thinking about your executive role in these terms: Conceptualize work mandates as projects; choose people who are better than you for your team; and try to work yourself out of a job. By learning to delegate, physician executives can make their own careers (as well as those on their team) richer and more fulfilled.

Career Mobility↗
PubMed2001

[Examination, treatment and follow-up of ovarian cancer in Norway].

BACKGROUND: In order to improve our knowledge about the medical examination, treatment and follow of cancer patients, suggestions have been put forward for a system for quality assurance of clinical data on cancer in Norway (Government White Paper 20: 1997). MATERIAL AND METHODS: In spring 2000, a questionnaire was sent to 41 gynaecological departments with focus on ovarian cancer patients. Four of the departments were regional cancer centres. RESULTS: All gynaecological departments answered the questionnaire. Standard gynaecological examination, vaginal ultrasonography and CA-125 determination were included in the diagnostic procedures in all departments. Some differences were detected: Cytological examination of pleural effusions as part of the staging procedure was not performed by all hospitals. In one health region, hospitals used a Risk of Malignancy Index for referring women with suspected malignant pelvic masses to a centralised gynaecologic oncology unit for primary surgery. Sixteen hospitals out of 37 operated on patients with FIGO stage I disease without performing lympadenectomy. When operating on suspected FIGO stage II-IV disease, three out of 22 local hospitals never performed surgery of the intestines in order to achieve optimal tumour reduction. All regional hospitals gave adjuvant chemotherapy to high-risk FIGO stage I patients. Standard treatment in advanced stages was paclitaxel/carboplatinum. Some hospitals participated in randomized trials on chemotherapy. Third-line treatment depended on the patient's condition, earlier toxicity and response. One regional centre preferred not to give any third-line chemotherapy. Only a few hospitals recorded the patient's performance status (WHO or Karnofsky's grading table) during the treatment and follow-up. Most of the gynaecological departments referred the patients to the regional hospital at the time of recurrence. About half of the outpatient departments gave a written report to the regional hospital. INTERPRETATION: There are differences between the hospitals in how they handle ovarian cancer patients. One cannot, however, determine from this inquiry what kind of medical examination, treatment and follow-up is best. An extended registration of ovarian cancer organised by the Cancer Registry of Norway will be started with the aim of providing reliable population-based data (the OVANOR project).

Antineoplastic Agents↗
PubMed1989

Biologicals production by recombinant DNA technology in Cuba.

During 1981 we started an intensive programme for the development of biotechnology in Cuba. The first project was related to the production of leucocyte interferon and the cloning an expression of these genes in prokaryotic and yeast cells. These products are currently obtained in large amounts and their physical and chemical characterization are presented. The use of mammalian cells in culture for the production of recombinant proteins has also been carried out. The results obtained with the expression and amplification of the hepatitis B surface antigen (HBsAg) in CHO cells are discussed and compared with that obtained in yeast. The construction of a recombinant vaccinia virus carrying the HBsAg was also achieved. The specific transcripts were characterized and the Ab levels tested in animals. The results presented here indicate that the host system is a very important aspect to be taken into consideration and in some cases mammalian cells appear to be the best choice.

Animals↗
PubMed1994

[Primary health care and community participation: strategic approaches].

This article gives technical orientation to health institutions for the promotion of community participation and sets forth the challenge of constructing a health system for Chile, according to the needs and problems of the country and based on the principles of solidarity, equity and social participation. It presents the governmental objectives and actions towards the development of social participation as an axis of Primary Care. The adoption of this concept requires a change in health teams internal management and relationship with the local community. The formation of interdisciplinary work groups, the formulation of a community health program, a work based in specific projects and the establishment of an operational sequence are suggested as requirements to start this process.

Chile↗
PubMed1998

[The EUROPOP Project. European Programme of Occupational Risks and Pregnancy Outcomes].

Efforts to obtain an objective view of the working and living conditions of European women and in particular the influence of these conditions on the course of pregnancy were the reason why in 1994 within research activities of the EC a project EUROPOP (European Programme of Occupational Risk and Pregnancy Outcome) was adopted and started. Seventeen countries incl. the Czech Republic were asked to participate. The research proper was conducted in 57 maternity institutions. In the Czech Republic the Olomouc region was selected with the Gynaecological and Obstetric Clinic in Olomouc as the coordinating centre. All 13 gynaecological and obstetric departments of the Olomouc catchment area were included in the trial.

Europe↗
PubMed2000

Science, art and drug discovery: a personal perspective.

The research programme that started in 1985 led to the approval of Sildenafil (Viagra), in 1998, as the first oral treatment for male erectile dysfunction. The initial project objective was the design and synthesis of novel inhibitors of phosphodiesterase that would increase tissue levels of cGMP, and that could be beneficial for the treatment of cardiovascular conditions. Starting from zaprinast, a weak phosphodiesterase inhibitor, computer modelling guided rational medicinal chemistry to achieve significant increases in potency and selectivity for the 5-isoenzyme within a novel series of pyrazolopyrimidinones. Optimization of structure-activity relationships and pharmacokinetic properties led to sildenafil, which proved essentially devoid of cardiovascular activity in clinical trials. However, the emerging role of nitric oxide and cGMP in controlling blood flow in the penis suggested that sildenafil would have a beneficial effect on erectile function. This hypothesis was confirmed by extensive clinical trials in nearly 5000 patients and the Food and Drug Administration approved sildenafil in March 1998 for male erectile dysfunction. Sildenafil is now available in over 100 countries and more than 150 million tablets have been dispensed worldwide. The sildenafil research programme reflects a traditional approach to drug discovery, but pressures to improve productivity have prompted major investments in genome sciences and new technologies. The impact of these initiatives on the drug discovery paradigm will be discussed, particularly with respect to shortening time scales between identifying gene sequences and submitting innovative products for regulatory approval.

Clinical Trials as Topic↗