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Management of fire blight: a case study in microbial ecology.

Suppression of the blossom-blight phase of fire blight is a key point in the management of this destructive and increasingly important disease of apple and pear. For blossom infection to occur, the causal bacterium, Erwinia amylovora, needs to increase its population size through an epiphytic phase that occurs on stigmatic surfaces. Knowledge of the ecology of the pathogen on stigmas has been key to the development of predictive models for infection and optimal timing of antibiotic sprays. Other bacterial epiphytes also colonize stigmas where they can interact with and suppress epiphytic growth of the pathogen. A commercially available bacterial antagonist of E. amylovora (BlightBan, Pseudomonas fluorescens A506) can be included in antibiotic spray programs. Integration of bacterial antagonists with chemical methods suppresses populations of the pathogen and concomitantly, fills the ecological niche provided by the stigma with a nonpathogenic, competing microorganism. Further integration of biologically based methods with conventional management of blossom blight may be achievable by increasing the diversity of applied antagonists, by refining predictive models to incorporate antagonist use, and by gaining an improved understanding of the interactions that occur among indigenous and applied bacterial epiphytes, antibiotics, and the physical environment.

Journal Article↗

Computer-assisted stereotactic biopsy of intracranial lesions in pediatric patients.

A computer-assisted stereotactic biopsy technique has been used in 30 patient (ages 5 months to 16 years) with intracranial lesions (supratentorial in 23 and infratentorial in 7). The computer program integrates stereotactically gathered imaging data and permits preoperative planning of a biopsy trajectory. Diagnostic tissue was obtained in 27 cases. In 2 cases, therapeutic interventions--third ventriculostomy and cyst aspiration--were accomplished at the time of the biopsy. There were no major complications related to the procedure; however, 2 patients had transient neurologic deficits. Computer-assisted stereotactic biopsy is a valuable diagnostic procedure in the pediatric patient with an intracranial lesion.

Adolescent↗

Early signals in cardiac development.

The heart is the first organ to form during embryogenesis and its circulatory function is critical from early on for the viability of the mammalian embryo. Developmental abnormalities of the heart have also been widely recognized as the underlying cause of many congenital heart malformations. Hence, the developmental mechanisms that orchestrate the formation and morphogenesis of this organ have received much attention among classical and molecular embryologists. Due to the evolutionary conservation of many of these processes, major insights have been gained from the studies of a number of vertebrate and invertebrate models, including mouse, chick, amphibians, zebrafish, and Drosophila. In all of these systems, the heart precursors are generated within bilateral fields in the lateral mesoderm and then converge toward the midline to form a beating linear heart tube. The specification of heart precursors is a result of multiple tissue and cell-cell interactions that involve temporally and spatially integrated programs of inductive signaling events. In the present review, we focus on the molecular and developmental functions of signaling processes during early cardiogenesis that have been defined in both vertebrate and invertebrate models. We discuss the current knowledge on the mechanisms through which signals induce the expression of cardiogenic transcription factors and the relationships between signaling pathways and transcriptional regulators that cooperate to control cardiac induction and the formation of a linear heart tube.

Animals↗

Thrombopoietin protects against in vitro and in vivo cardiotoxicity induced by doxorubicin.

BACKGROUND: Doxorubicin (DOX) is an important antineoplastic agent. However, the associated cardiotoxicity, possibly mediated by the production of reactive oxygen species, has remained a significant and dose-limiting clinical problem. Our hypothesis is that the hematopoietic/megakaryocytopoietic growth factor thrombopoietin (TPO) protects against DOX-induced cardiotoxicity and might involve antiapoptotic mechanism exerted on cardiomyocytes. METHODS AND RESULTS: In vitro investigations on H9C2 cell line and spontaneously beating cells of primary, neonatal rat ventricle, as well as an in vivo study in a mouse model of DOX-induced acute cardiomyopathy, were performed. Our results showed that pretreatment with TPO significantly increased viability of DOX-injured H9C2 cells and beating rates of neonatal myocytes, with effects similar to those of dexrazoxane, a clinically approved cardiac protective agent. TPO ameliorated DOX-induced apoptosis of H9C2 cells as demonstrated by assays of annexin V, active caspase-3, and mitochondrial membrane potential. In the mouse model, administration of TPO (12.5 microg/kg IP for 3 alternate days) significantly reduced DOX-induced (20 mg/kg) cardiotoxicity, including low blood cell count, cardiomyocyte lesions (apoptosis, vacuolization, and myofibrillar loss), and animal mortality. Using Doppler echocardiography, we observed increased heart rate, fractional shortening, and cardiac output in animals pretreated with TPO compared with those receiving DOX alone. CONCLUSIONS: These data have provided the first evidence that TPO is a protective agent against DOX-induced cardiac injury. We propose to further explore an integrated program, incorporating TPO with other protocols, for treatment of DOX-induced cardiotoxicity and other forms of cardiomyopathy.

Animals↗

Improving medication compliance of a patient with schizophrenia through collaborative behavioral therapy.

Introduction by the column editors: Numerous factors influence a patient's decision to accept or reject prescribed medications, including the patient's personal values, environmental conditions, and the quality of the patient-physician relationship (1). Guidelines for evaluating and managing noncompliance with medication regimens by patients with schizophrenia take this multidimensional perspective into account, emphasizing functional assessment of nonadherence behaviors and individualized behavior-change strategies to secure and maintain the patient's cooperation (2). Moreover, a collaborative approach to planning pharmacotherapy is required to ensure medication compliance, with a particular emphasis on linking the positive effects of medications with the patient's personal goals and desires for better functioning and quality of life (3). The following case study illustrates the application of principles for enhancing medication compliance in the treatment of a woman diagnosed as having schizophrenia, paranoid type. Strategies presented by Dr. Heinssen include collaborative treatment contracts, analysis of adherence behaviors, and techniques for boosting medication cues and reinforcers in the patient's home. The therapy described was provided in the Life Skills partial hospitalization and psychiatric rehabilitation program, a multidisciplinary, multilevel outpatient service of the now-closed Chestnut Lodge Hospital in Rockville, Maryland. The program integrated medical, social-learning, and cognitive-behavioral interventions for psychosis within a psychiatric rehabilitation framework.

Cognitive Behavioral Therapy↗

Two genealogies of supported housing and their implications for outcome assessment.

Drawing on ongoing fieldwork in New York City, the authors distinguish two "genealogies," or developmental traditions, of supported housing. "Housing as housing" originated in the mental health field to champion normalized, less-structured alternatives to clinically managed residential programs. "Integrated housing development" traces its origins to the movement to combat homelessness by preserving and creating affordable housing. The authors detail the distinctive premises, guiding concerns, and developmental logic of each lineage, contrasting the consumer advocate focus of the first genealogy with the emphasis on housing supply of the second. As housing and service investment strategies, the two approaches run different risks, speak to distinctive constituencies, and play to specific strengths. The authors argue that any attempt to take the measure of their success or to assess their comparative value as social investments must go beyond client outcome and come to terms with discrepant notions of the social good that they represent.

Community Mental Health Services↗

The clinical strategies implementation scale to measure implementation of treatment in mental health services.

OBJECTIVE: The authors describe the development of the Clinical Strategies Implementation Scale (CSI), an instrument designed to help providers measure the extent to which evidence-based strategies have been implemented in the treatment of persons with schizophrenia spectrum disorders. METHODS: Nine ordinal scales were devised to measure key aspects of treatment strategies that have been associated with clinical and social recovery from schizophrenia: goal- and problem-oriented assessment, medication strategies, assertive case management, mental health education, caregiver-based problem solving, living skills training, psychological strategies for residual problems, crisis prevention and intervention, and booster sessions. A study of interrater reliability was conducted with 15 trained raters from participating centers in Athens, Auckland, Bonn, Budapest, Gothenburg, and Tokyo who assessed 54 cases. Each treatment strategy was weighted according to its effect size in clinical trials. Correlation analyses were conducted to explore associations between the total CSI score and ratings of clinical, social, and caregiver outcomes each year over four years of continued treatment of 51 patients. RESULTS: Interrater reliability ranged from .93 to .99. Four annual total CSI ratings were significantly correlated with impairment, disability, functioning, work activity, and an index of recovery. Most correlations were stronger in years 3 and 4 than in years 1 and 2. CONCLUSIONS: Reliable and valid assessment of the implementation of evidence-based strategies in clinical practice is feasible. The quality of integrated program implementation may be associated with improved clinical and social recovery from schizophrenic disorders.

Evidence-Based Medicine↗

Goal structure effects on social interaction: nondisabled and disabled elementary students.

This study compared social interaction behavior between nondisabled and disabled students, as a function of the way tasks were structured during a peer integration program. Of the eight pairs of students, four pairs were assigned to an individualistic goal-structured condition; the other four pairs, to a cooperative condition. For nondisabled students, the cooperative condition was associated with more social interaction during activity and free play sessions. For disabled students, the cooperative condition was associated with more social interaction during activity sessions, but not during free play sessions.

Adolescent↗

Korean American family experiences of caregiving for their mentally ill adult children: an interpretive inquiry.

The purpose of this cross-cultural qualitative study is to describe and interpret the Korean American families' (KAFs') caregiving experiences for their mentally ill grown children. Seven KAF caregivers were purposefully sampled. In-depth audiotaped interviews were conducted in Korean, and Korean metaphors, images, and dreams were translated into English. This allowed for a rich explication of this study's complex caregiving phenomena. Five major themes were identified: (a) realization of children's illness, (b) battling the disease of incompetence, (c) poignant processes of caregiving, (d) suffering as a way of life, and (e) journey toward spirituality. In conclusion, incorporating transcultural nursing into core nursing curricula, recognizing the spiritual dimensions of care in nursing, and establishing culturally congruent community-based day treatment modalities and programs integrating other cultures are recommended.

Adult↗

AIDS and hospice.

Which AIDS patients should be admitted to hospice programs? Many health care professionals feel that any anti-viral drug or treatment directed against the opportunistic infections characteristic of AIDS to be incompatible with hospice philosophy. Others argue that inclusion of AIDS patients blurs the distinction between hospice and community service programs. We argue that achieving consensus on this issue is best served by focusing on the defining characteristic of hospice programs--the care of the dying. Consensus is not served by dwelling on the specific palliative or supportive measures used to achieve the hospice goal. We suggest a framework by which AIDS patients may be accommodated in existing hospice programs while maintaining hospice program integrity. It is further suggested that these may be used for the consideration of any patient for hospice care.

Acquired Immunodeficiency Syndrome↗

Application of cost-benefit and cost-effectiveness analysis to clinical practice.

This article is intended to introduce the reader to the concepts of CEA/CBA for purposes of evaluating innovative pharmacy services. Furthermore, sensitization to the issues surrounding CEA/CBA studies should allow the reader to be more discriminating in reviewing such reports in the literature. Rising costs for health care and the existence of limited resources are forcing policy makers to allocate resources in ways that maximize return-on-investment. It is felt by some that in the 1980s, researchers will be expected to answer the questions, "How much better is the innovation?" and "How do the expected benefits of an innovation compare with the benefits that could be obtained if the resources were used in some alternative way?" Part of the solution will require changes in the training and practice of health professionals. Future physicians, pharmacists, and others will need to acquire skills from the behavioral, social, and decision sciences (e.g., epidemiology, statistics, economics, decision analysis). The notion of cost-effective clinical decision making needs to be taught at all levels. Health practitioners involved with decision making at the level of the patient need to become more knowledgeable of the overall impact (regarding costs and benefits) of their decisions. Finally, evaluation of innovative pharmacy services is but one element of a management program for clinical services. Our attempt is not to deemphasize the need for studies documenting the value of clinical services, but rather to put evaluation in perspective with an equally important need, the need for development of an overall pharmacy program that is not only cost effective but efficient as well. The means to this end is a total management program integrating all pharmacy services.

Cost-Benefit Analysis↗

A computerized intensive care unit order-writing protocol.

OBJECTIVE: To present a computerized intensive care unit order-writing protocol. DESIGN: Descriptive report. SETTING: Eight-bed surgical intensive care unit, Department of Surgery, Department of Veterans Affairs Medical Center, Bronx, NY. METHODS: IBM-based, computer network program that provides user-friendly, logical, and comprehensive organ-system order sequences for patient management. RESULTS: Since July 1988, an order program that stresses (1) improved and more efficient patient care, (2) the use of program-integrated automatic safety features, (3) the substitution of computer entry for handwriting, and (4) the assurance that physicians deliver obligatory care in a logical organ-system-based progression has been implemented. CONCLUSIONS: The order protocol system presented is simple to introduce and operate, has minimal training and technical requirements, and is demonstrably reliable.

Computer Security↗

Pharmacist-led, primary care-based disease management improves hemoglobin A1c in high-risk patients with diabetes.

We developed and evaluated a comprehensive pharmacist-led, primary care-based diabetes disease management program for patients with Type 2 diabetes and poor glucose control at our academic general internal medicine practice. The primary goal of this program was to improve glucose control, as measured by hemoglobin A1c (HbA1c). Clinic-based pharmacists offered support to patients with diabetes through direct teaching about diabetes, frequent phone follow-up, medication algorithms, and use of a database that tracked patient outcomes and actively identified opportunities to improve care. From September 1999, to May 2000, 159 subjects were enrolled, and complete follow-up data were available for 138 (87%) patients. Baseline HbA1c averaged 10.8%, and after an average of 6 months of intervention, the mean reduction in HbA1c was 1.9 percentage points (95% confidence interval, 1.5-2.3). In predictive regression modeling, baseline HbA1c and new onset diabetes were associated with significant improvements in HbA1c. Age, race, gender, educational level, and provider status were not significant predictors of improvement. In conclusion, a pharmacist-based diabetes care program integrated into primary care practice significantly reduced HbA1c among patients with diabetes and poor glucose control.

Academic Medical Centers↗

Intra-operative central vein angioplasty during arteriovenous access creation.

Central vein stenosis or occlusion due to prior use of central vein hemodialysis catheters may lead to disabling extremity edema or cause early failure after arteriovenous access construction. Our integrated program for arteriovenous access management enables us to identify these stenoses pre-operatively. We carried out intra-operative angiography and angioplasty during arteriovenous access creation in 3 patients with good immediate and long-term results. Intra-operative endovascular therapy is a new application of peripheral vascular surgery techniques for patients with significant central vein stenosis undergoing access surgery, which exploits the high postoperative flow state to maintain patency after angioplasty. It may also be applicable in situations such as proximal arterial stenosis with anticipated steal syndrome and other conditions that may compromise access patency.

Journal Article↗

Metastatic breast cancer in a 54-year-old woman: integrative treatment with yttrium-90 radioembolization.

In 1993, a 54-year-old woman was diagnosed with early-stage breast adenocarcinoma and treated with doxorubicin and cyclophosphamide followed by tamoxifen. Nine years later, the patient presented for integrative treatment, with liver metastases. Carcinoembryonic antigen was significantly elevated. The patient was started on a heavily fractionated, multiple-agent chemotherapy regimen; however, she underwent significant adverse effects and the treatment was suspended. She then started on intravenous nutrition along with specific nutritional supplements. Two months later, a similar chemotherapeutic regimen was started in association with her existing nutritional protocol. One month later, the carcinoembryonic antigen began to rise, and a positron emission tomography scan was ordered that revealed the persistence of multiple and extensive liver metastases as well as possible skeletal metastases. The patient was started on an oral bisphosphonate and referred to interventional radiology for consultation on radioembolization with yttrium-90. After being accepted for treatment, the patient under-went a right hepatic lobe angiogram and radioembolization. Within 2 weeks, she realized significant improvements in her clinical and laboratory status; chemotherapy was discontinued. She later underwent radioembolization to her left lobe. Thirteen months after the yttrium-90 treatment, the patient remains on an integrative program with radiographically and clinically stable disease.

Adenocarcinoma↗

cGMP-independent nitric oxide signaling and regulation of the cell cycle.

BACKGROUND: Regulatory functions of nitric oxide (NO*) that bypass the second messenger cGMP are incompletely understood. Here, cGMP-independent effects of NO* on gene expression were globally examined in U937 cells, a human monoblastoid line that constitutively lacks soluble guanylate cyclase. Differentiated U937 cells (>80% in G0/G1) were exposed to S-nitrosoglutathione, a NO* donor, or glutathione alone (control) for 6 h without or with dibutyryl-cAMP (Bt2cAMP), and then harvested to extract total RNA for microarray analysis. Bt2cAMP was used to block signaling attributable to NO*-induced decreases in cAMP. RESULTS: NO* regulated 110 transcripts that annotated disproportionately to the cell cycle and cell proliferation (47/110, 43%) and more frequently than expected contained AU-rich, post-transcriptional regulatory elements (ARE). Bt2cAMP regulated 106 genes; cell cycle gene enrichment did not reach significance. Like NO*, Bt2cAMP was associated with ARE-containing transcripts. A comparison of NO* and Bt2cAMP effects showed that NO* regulation of cell cycle genes was independent of its ability to interfere with cAMP signaling. Cell cycle genes induced by NO* annotated to G1/S (7/8) and included E2F1 and p21/Waf1/Cip1; 6 of these 7 were E2F target genes involved in G1/S transition. Repressed genes were G2/M associated (24/27); 8 of 27 were known targets of p21. E2F1 mRNA and protein were increased by NO*, as was E2F1 binding to E2F promoter elements. NO* activated p38 MAPK, stabilizing p21 mRNA (an ARE-containing transcript) and increasing p21 protein; this increased protein binding to CDE/CHR promoter sites of p21 target genes, repressing key G2/M phase genes, and increasing the proportion of cells in G2/M. CONCLUSION: NO* coordinates a highly integrated program of cell cycle arrest that regulates a large number of genes, but does not require signaling through cGMP. In humans, antiproliferative effects of NO* may rely substantially on cGMP-independent mechanisms. Stress kinase signaling and alterations in mRNA stability appear to be major pathways by which NO* regulates the transcriptome.

Blotting, Western↗

Play, creativity, and adaptive functioning: implications for play interventions.

Discussed the importance of play in creative problem solving and its implications for play interventions. Theory and research in the areas of play and creative cognitive processes and play and creative affective processes are reviewed. Play has been associated with the development of creative problem solving. Creative problem solving is thought to be a resource for everyday coping and adjustment. Play intervention studies that investigate the effects of specific aspects of play on specific criteria would be appropriate for the creative problem-solving and coping area. A systematic program integrating laboratory research on play and creativity, research on play techniques, and play intervention with specific populations is needed.

Adaptation, Psychological↗

Chronic pain: from theory to practical management.

The neurologist is an important part of the pain management team. Factors that can alter presentation and complicate establishing a diagnosis are reviewed. A multidisciplinary approach to evaluation is advocated, particularly the inclusion of independent psychiatric or psychological evaluation. Treatment planning consists of addressing potential sources of failure of pain management, setting appropriate goals, and using the diagnostic assessment to plan pharmacologic and nonpharmacologic interventions based on pain mechanisms. Even if pharmacologic interventions do not alter pain, an education-oriented behavioral pain program integrated with physical therapy can improve function and foster self-reliance in controlling pain.

Animals↗