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PubMed2004

Identification of new Th peptides from the cytomegalovirus protein pp65 to design a peptide library for generation of CD4 T cell lines for cellular immunoreconstitution.

CD8 and CD4 lymphocytes control cytomegalovirus (CMV) infection in immunocompetent individuals, while patients with defective cellular immunity are prone to endogenous reactivation of latent CMV or, like seronegative subjects, prone to primary infection. Administration of CMV-specific CD8 lymphocytes was beneficial for immunocompromised hemopoietic stem cell (HSC) graft recipients. Since CD4 cells contribute to expansion of cytotoxic T lymphocytes (CTL), we defined new T(h) peptides on the immunodominant protein pp65 recognized by CD4 cells from HLA-typed subjects, in the perspective of complementing CTL administration with CMV-specific T(h) cells. Screening by ELISPOT on CD4 and CD8 subsets using overlapping peptides identified 10 novel CD4 peptides. To simplify procedures to generate T cell lines, we used a CD4 peptide library for T cell stimulation instead of ill-defined viral lysates, without the requirement of dendritic cells. This library stimulated CMV-specific CD4 cells. In fact, peptide-induced CD4 cells responded to pp65 and to the viral lysate. These cells were also devoid of alloreactivity after one stimulation cycle. Since Good Manufacturing Procedure-grade peptides can be synthesized, culture conditions are simplified and alloreactivity is rapidly lost, these procedures based on peptide stimulation can facilitate implementation of adoptive reconstitution of CD4 responses in immunocompromised patients also in the case when the HSC allodonor is available for generation of the T cell line.

Adolescent↗

PubMed1971

Cost-performance analysis of TWX-mediated interlibrary loans in a medium-sized medical center library.

The need for a cost-performance analysis of TWX-mediated versus mail-mediated ILL requests is presented. Three hypotheses are proposed: (1) Unit cost for TWX-mediated ILL requests is greater then for mail-mediated ILL requests; (2) Completion time is shorter for TWX-mediated ILL requests than for mail-mediated ILL requests; (3) An analytic model can be developed that can be used to generate administrative data concerning a TWX installation. The data presented support all three hypotheses. It is shown, also, that through the use of this model a library can arrive at a cost for service of TWX versus mail-mediated ILL.

Colorado↗

PubMed2002

Early surfactant administration with brief ventilation vs selective surfactant and continued mechanical ventilation for preterm infants with or at risk for RDS.

BACKGROUND: Both early and prophylactic surfactant replacement therapy compared with later selective surfactant administration reduces mortality and pulmonary complications in ventilated infants with respiratory distress syndrome (RDS). Continuous distending pressure (CDP) has also been shown to improve clinical outcomes in preterm infants with RDS. OBJECTIVES: To compare two treatment strategies in preterm infants with, or at risk for, RDS: early surfactant administration with brief mechanical ventilation (less than 1 hour) followed by extubation, vs later, selective surfactant administration, continued mechanical ventilation and extubation from low respiratory support. Two populations of infants receiving early surfactant were considered: spontaneously breathing infants with signs of RDS (surfactant administration during evolution of RDS prior to requiring intubation for respiratory failure) and infants at high risk for RDS (prophylactic surfactant administration within 15 minutes after birth). SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal trials, MEDLINE (1966-December 2001), CINAHL (1982-December 2001), EMBASE (1980-December 2001), Cochrane Controlled Trials Register (The Cochrane Library, Issue 1, 2002), Pediatric Research (1990-2001), abstracts, expert informants and hand searching. No language restrictions were applied. SELECTION CRITERIA: Randomized or quasi-randomized controlled clinical trials comparing early surfactant administration with planned brief mechanical ventilation (less than one hour) followed by extubation, vs selective surfactant administration, continued mechanical ventilation and extubation from low respiratory support. DATA COLLECTION AND ANALYSIS: Data were sought regarding effects on incidence of mechanical ventilation (ventilation continued or initiated beyond one hour after surfactant administration), incidence of bronchopulmonary dysplasia (BPD, need for oxygen at 28 days of age), incidence of chronic lung disease (CLD, need for oxygen at 36 weeks' post-conceptional age), mortality (neonatal mortality < 28 days and mortality prior to hospital discharge), duration of mechanical ventilation, duration of hospitalization, time in oxygen, duration of respiratory support (including CPAP and nasal cannula), number of patients receiving surfactant, number of surfactant doses administered per patient, incidence of air leak syndromes (pulmonary interstitial emphysema, pneumothorax), incidence of pulmonary hemorrhage, and other complications of prematurity. Data analyses were performed in accordance with the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: Only one randomized controlled clinical trial met selection criteria and was included in this review (Verder 1994). In this study of infants with signs of RDS, intubation and early surfactant therapy followed by extubation to nasal CPAP (NCPAP) compared with later, selective surfactant administration was associated with a lower incidence of mechanical ventilation (ventilation continuing for one hour or more after surfactant administration in the early surfactant group or initiated for respiratory insufficiency or apnea in either group [RR 0.51, 95% CI 0.32, 0.76]). A larger proportion of infants in the early surfactant group received surfactant than in the selective surfactant group [RR 1.74, 95% CI 1.30, 2.33]. The number of surfactant doses per patient was significantly greater among patients randomized to the early surfactant group [MD 0.51, 95% CI 0.32, 0.70]. Trends towards a decreased incidence of mortality, and a higher rate of patent ductus arteriosus requiring treatment were seen in the early surfactant group. There was no evidence of effect on median time in oxygen, duration of mechanical ventilation, or incidence of BPD (oxygen at 28 days). REVIEWER'S CONCLUSIONS: Early surfactant replacement therapy with extubation to NCPAP compared with later, selective surfactant replacement and continued mechanical ventilation with extubation from low ventilator support is associated with a reduced need for mechanical ventilation and increased utilization of exogenous surfactant therapy. These conclusions are based on findings from one small randomized clinical trial. Additional randomized trials are needed and are underway.

Combined Modality Therapy↗

PubMed2006

Perioperative glucocorticoid administration for prevention of systemic organ failure in patients undergoing esophageal resection for esophageal carcinoma.

CONTEXT AND OBJECTIVE: Preoperative glucocorticoid administration has been proposed for reducing postoperative morbidity. This is not widely used before esophageal resection because of incomplete knowledge regarding its effectiveness. The aim here was to assess the effects of preoperative glucocorticoid administration in adults undergoing esophageal resection for esophageal carcinoma. SEARCH STRATEGY: Studies were identified by searching the Cochrane Controlled Trials Register, MEDLINE, EMBASE, Cancer Lit, SCIELO and Cochrane Library, and by manual searching from relevant articles. The last search for clinical trials for this systematic review was performed in December 2004. SELECTION CRITERIA: This review included randomized studies of patients with potentially resectable carcinomas of the esophagus that compared preoperative glucocorticoid administration with placebo. DATA COLLECTION AND ANALYSIS: Data were extracted by the same reviewers, and the trial quality was assessed using Jadad scoring. Relative risk and weighted mean difference with 95% confidence limits were used to assess the significance of the difference between the treatment arms. RESULTS: Four randomized trials involving 146 patients were found. There were no differences in postoperative mortality, sepsis, anastomotic leakage, hepatic and renal failure between the glucocorticoid and placebo groups. There were fewer postoperative respiratory complications (p = 0.005) and multiple postoperative complications (p = 0.004) and lower postoperative plasma interleukin-6 levels (p = 0.00001) with preoperative glucocorticoid administration. There was a higher postoperative PaO2/FiO2 ratio (p = 0.0001) with preoperative glucocorticoid administration. CONCLUSION: Prophylactic administration of glucocorticoids is associated with decreased postoperative complications.

Carcinoma↗

PubMed2005

Use of herbal therapies to relieve pain: a review of efficacy and adverse effects.

To find holistic treatment with effective pain relief and few side effects, Americans spend billions of dollars annually on complementary and alternative medicine, including herbal therapies. Despite extensive use, the lack of regulatory scrutiny of these herbal supplements contributes to the paucity of reliable clinical data assessing their efficacy and safety. This review summarizes the existing studies investigating the efficacy of herbal therapies as a treatment for pain. Possible side effects, potential drug-herb interactions, and information about common herbal therapies are also summarized. MEDLINE, AMED, and the Cochrane Library databases were searched for the period from January 1966 to June 2005. Uses, dosages, routes of administration, and side effects were summarized. Strength of empirical evidence also was evaluated. This review found few well-controlled clinical studies. Furthermore, these studies documented limited efficacy of herbal therapies to treat pain. The information presented here may be used to further educate nurses and patients on the use of herbal therapies as well as direct future research efforts.

Clinical Trials as Topic↗

PubMed2004

Evaluation of HIV/AIDS prevention resources in Liberia: strategy and implications.

The purpose of this preliminary study was to assess the HIV/AIDS prevention needs, services, and resources in Liberia, including the readiness of local providers to conduct HIV/AIDS-related prevention programs based on a set of six key dimensions (prevention needs, knowledge, leadership, environment, risky behaviors, and resources). A valid self-administered qualitative-based health survey, based on a community readiness model, was utilized as the primary data collection source. A cross-sectional design that utilized a convenient sample of key informants such as health coordinators, program directors, and health administrator from both public and private HIV/AIDS-based organizations was used. Furthermore, an extensive review of the National Library of Medicine database of published articles from mid-1980 to 2002 was simultaneously conducted to gauge the extent of scientific publications on HIV/AIDS-related prevention services in Liberia. The findings from this study strongly suggest that Liberia is in a stage of vague awareness, as defined by the Tri-Ethnic Center community readiness framework, regarding HIV/AIDS-related activities, including a significant lack of HIV/AIDS-related resources and scientific publications. Accordingly, there is a critical need to acquire adequate resources and build capacity to implement effective HIV/AIDS-related prevention programming services in order to avert the negative public health consequences associated with HIV/AIDS, including the implementation of relevant evaluation and dissemination strategies. Most importantly, this model has the potential to be utilized in other resource-constraint settings, especially in the developing world, to assess prevention-related resources and programmatic readiness. This is the first published study to evaluate Liberia's HIV/AIDS prevention resources and to systematically document the extent and magnitude of the HIV/AIDS crises in the country.

HIV Infections↗

PubMed2001

Are cannabinoids an effective and safe treatment option in the management of pain? A qualitative systematic review.

OBJECTIVE: To establish whether cannabis is an effective and safe treatment option in the management of pain. DESIGN: Systematic review of randomised controlled trials. DATA SOURCES: Electronic databases Medline, Embase, Oxford Pain Database, and Cochrane Library; references from identified papers; hand searches. STUDY SELECTION: Trials of cannabis given by any route of administration (experimental intervention) with any analgesic or placebo (control intervention) in patients with acute, chronic non-malignant, or cancer pain. Outcomes examined were pain intensity scores, pain relief scores, and adverse effects. Validity of trials was assessed independently with the Oxford score. DATA EXTRACTION: Independent data extraction; discrepancies resolved by consensus. DATA SYNTHESIS: 20 randomised controlled trials were identified, 11 of which were excluded. Of the 9 included trials (222 patients), 5 trials related to cancer pain, 2 to chronic non-malignant pain, and 2 to acute postoperative pain. No randomised controlled trials evaluated cannabis; all tested active substances were cannabinoids. Oral delta-9-tetrahydrocannabinol (THC) 5-20 mg, an oral synthetic nitrogen analogue of THC 1 mg, and intramuscular levonantradol 1.5-3 mg were about as effective as codeine 50-120 mg, and oral benzopyranoperidine 2-4 mg was less effective than codeine 60-120 mg and no better than placebo. Adverse effects, most often psychotropic, were common. CONCLUSION: Cannabinoids are no more effective than codeine in controlling pain and have depressant effects on the central nervous system that limit their use. Their widespread introduction into clinical practice for pain management is therefore undesirable. In acute postoperative pain they should not be used. Before cannabinoids can be considered for treating spasticity and neuropathic pain, further valid randomised controlled studies are needed.

Analgesics, Non-Narcotic↗

PubMed2000

Identification of peptide motifs recognized by a human IgG autoanti-IgE antibody using a phage display library.

BACKGROUND: The potential of murine monoclonal anti-IgE antibodies as long-term therapy for atopic diseases will have to rely, for the time being, on passive antibody administration. There is therefore considerable interest in developing a peptide-based vaccine for active immunization to elicit long-term protective anti-IgE antibodies in the patient. It has been shown that some human IgG autoanti-IgE antibodies have the ability to partially block the binding of IgE to Fc receptors such as Fc epsilonRI. Therefore, the epitopes recognized by such antibodies could have vaccine potential. OBJECTIVE: To determine the epitope specificity of one such human IgG anti-IgE antibody. METHODS: A 15-mer phage-peptide library was used to establish the epitope specificity of an IgG anti-IgE antibody isolated from the serum of an asthma patient. RESULTS: The SRPSP sequence, or part of it (i.e. RPS, RPSP, SPS or PSP), was present in all 18 phage-peptides that have been sequenced. This common motif was found to be within the human epsilon chain sequence Ser341-Thr355 near the N-terminus of the C epsilon3 domain. According to the human Fc epsilon model, the most accessible residues in this sequence are Arg342, Ile350, Arg351, Lys352 and Ser353. CONCLUSIONS: The present data should provide the molecular basis for the rational design of a suitable peptide immunogen (vaccine) for boosting the production of protective autoanti-IgE antibodies.

Amino Acid Motifs↗

PubMed2006

Interactive tools for risk reduction and efficiency improvements in medicinal chemistry.

There are many decisions and risks associated with the design and development of new pharmaceutical agents. To help improve decision-making, and reduce the associated risks--prior to synthesis, we have developed interactive web-browser tools for: (i) tracking, searching, clustering and categorizing (by reactive moieties) chemical reactants, (ii) interactively assessing risks, either synthetic--based on prior experience, absorption following oral administration--based on rules of 5, or diversity, and (iii) a complete architecture for enumerating, analyzing, submitting and plating large combinatorial or small biased libraries. We believe the implementation of this highly interactive system has given our scientists a competitive advantage by maintaining their focus on the lowest risk, highest quality molecules throughout the research process.

Administration, Oral↗

PubMedDate not supplied

Medical journals of Nigeria, quo vadis?

The Nigerian health sector is beset with an underdeveloped Continuing Medical Education (CME) programme, a scarcity of reading materials and the lack of a reading culture. Recent issues of available journals were obtained and read to identify data such as: the ownership and base, presence of mission statement, print quality, administrative and editorial matters, abstract format, CME value of articles, advertisements, subscription information and communication channels and practice. The availability of the journals in the libraries of the three 'first generation' teaching hospitals and accessibility through the Medline were ascertained. Twenty-eight current journals were obtained. Lagos has the highest number of editorial bases. Fifteen journals belong to national medical associations, 2 to regions and 11 to institutions. The journal title was considered appropriate in 13, cover design was good in 15, paper quality was good in 20 and legibility was good in 11 journals. Poor editing was manifested by bad grammar, spelling and punctuation. Six journals contained review articles of good CME value. Eight journals had a full compliment of communication facilities. The existence of a functional independent administrative office or staff was indicated in 7 journals. No journal indicated the dates of submission and acceptance of articles. Twenty-one journals were on the shelf of the library of ABUTH, Zaria. Two journals are accessible through the Medline and another is on-line. Adequate funding and improved management will effectively address most of the problems identified.

Humans↗

PubMed1974

The place of the hospital library consortium in the National Biomedical Communications Network.

The National Library of Medicine has issued a policy statement outlining expectations of more self-sufficiency at the Basic Unit level than was required during earlier programs under the Medical Library Assistance Act. A consortium of hospital libraries is presented as one viable alternative for meeting NLM's expectations that hospital libraries serve the primary and most immediate information needs of their own constituencies. The Biomedical Communications Network is reviewed so that hospital administrators and librarians will have a more thorough understanding of the system which they should now enter as contributors rather than as recipients only. A Network configuration illustrating the interaction of Basic Units functioning in consortia relationships is presented, and general areas for sharing are discussed.

Biology↗

PubMed1995

Arizona Health Information Network: the collaborative administration and management of a statewide computing resource for health information.

The need to access current, relevant health care information transcends the boundaries of the library. Many computer-based tools are now available that provide access to this information where and when it is needed. However, the provision of these tools often requires a substantial commitment of resources in the form of staff expertise, computer hardware and software, and user training. The need to access current information is critical for health care providers and students at all points of care regardless of the institution size or location. Unfortunately, the resources necessary to provide access to information may not be equally available at all sites. The Arizona Health Information Network (AZHIN) joins together librarians and information systems specialists from eleven institutions throughout the state in an effort to share computing resources and expertise in order to improve the quality of health care delivery, education and research. This cooperative effort allows each institution to contribute both financially and in the form of staff expertise, based upon its size and available resources. Although the benefits of this type of cooperation seem obvious, in a competitive environment it is necessary for each member to retain independence. To balance cooperation and independence, a framework has been established to enable individual AZHIN member institutions to administer local access to the shared resources.

Academic Medical Centers↗

PubMed2004

Early surfactant administration with brief ventilation vs selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome.

BACKGROUND: Both prophylactic and early surfactant replacement therapy, compared with later selective surfactant administration, reduce mortality and pulmonary complications in ventilated infants with respiratory distress syndrome (RDS). However, continued post-surfactant intubation and ventilation are risk factors for chronic lung disease. Whether prophylactic or early surfactant administration followed by prompt extubation, compared with later, selective use of surfactant followed by continued mechanical ventilation reduces the need for mechanical ventilation and the incidence of chronic lung disease is unknown. OBJECTIVES: To compare two treatment strategies in preterm infants with, or at risk for, RDS: early surfactant administration with brief mechanical ventilation (less than one hour) followed by extubation, vs later, selective surfactant administration, continued mechanical ventilation and extubation from low respiratory support. Two populations of infants receiving early surfactant were considered: spontaneously breathing infants with signs of RDS (surfactant administration during evolution of RDS prior to requiring intubation for respiratory failure) and infants at high risk for RDS (prophylactic surfactant administration within 15 minutes after birth). SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal trials, MEDLINE (1966-December 2003), CINAHL (1982-December 2003), EMBASE (1980-December 2003), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2004), Pediatric Research (1990-2003), abstracts, expert informants and hand searching. No language restrictions were applied. SELECTION CRITERIA: Randomized or quasi-randomized controlled clinical trials comparing early surfactant administration with planned brief mechanical ventilation (less than one hour) followed by extubation, vs selective surfactant administration, continued mechanical ventilation and extubation from low respiratory support. DATA COLLECTION AND ANALYSIS: Data were sought regarding effects on incidence of mechanical ventilation (ventilation continued or initiated beyond one hour after surfactant administration), incidence of bronchopulmonary dysplasia (BPD), chronic lung disease (CLD), mortality, duration of mechanical ventilation, duration of hospitalization, time in oxygen, duration of respiratory support (including CPAP and nasal cannula), number of patients receiving surfactant, number of surfactant doses administered per patient, incidence of air leak syndromes (pulmonary interstitial emphysema, pneumothorax), patent ductus arteriosus requiring treatment, pulmonary hemorrhage, and other complications of prematurity. Treatment effect was expressed as relative risk (RR) and risk difference (RD) for categorical variables, and weighted mean difference (WMD) for continuous variables. MAIN RESULTS: Four randomized controlled clinical trials met selection criteria and were included in this review. In these studies of infants with signs of RDS, intubation and early surfactant therapy followed by extubation to nasal CPAP (NCPAP) compared with later selective surfactant administration was associated with a lower incidence of mechanical ventilation [typical RR 0.70, 95% CI 0.59, 0.84]. None of the trials reported a significant difference in the incidence of BPD or CLD; however, meta-analysis for this outcome cannot yet be performed because the primary data from three of the trials have not yet been published in full. A larger proportion of infants in the early surfactant group received surfactant than in the selective surfactant group [typical RR 1.59, 95% CI 1.35, 1.88]. The number of surfactant doses per patient was significantly greater among patients randomized to the early surfactant group [WMD 0.51 doses per patient, 95% CI 0.36, 0.65]. Trends towards a decreased incidence of air leak syndromes (two studies) and a higher incidence of patent ductus arteriosus requiring treatment (one study) were seen in the early surfactant group. There was no evidence of effect on time in oxygen or duration of mechanical ventilation. REVIEWERS' CONCLUSIONS: Early surfactant replacement therapy with extubation to NCPAP compared with later, selective surfactant replacement and continued mechanical ventilation with extubation from low ventilator support is associated with a reduced need for mechanical ventilation and increased utilization of exogenous surfactant therapy. There is insufficient evidence at present to reliably evaluate effect on BPD or CLD.

Humans↗

PubMed2000

Intravenous immunoglobulin for preventing infection in preterm and/or low-birth-weight infants.

BACKGROUND: Nosocomial infections continue to be a significant cause of morbidity and mortality among preterm and/or low birth weight infants. Maternal transport of immunoglobulins to the fetus mainly occurs after 32 weeks gestation and endogenous synthesis does not begin until several months after birth. Administration of intravenous immunoglobulin provides IgG that can bind to cell surface receptors, provide opsonic activity, activate complement, promote antibody dependent cytotoxicity, and improve neutrophilic chemoluminescence. Intravenous immunoglobulin thus has the potential of preventing or altering the course of nosocomial infections. OBJECTIVES: To assess the effectiveness/safety of intravenous immunoglobulin (IVIG) administration (compared to placebo or no intervention) to preterm (< 37 weeks gestational age at birth) and/or low birth weight (LBW) (< 2500 g BW) infants in preventing nosocomial infections. SEARCH STRATEGY: Medline, Embase, Cochrane Library and Reference Update Databases were searched in November 1997 using keywords: immunoglobulin and infant-newborn and random allocation or controlled trial or randomized controlled trial (RCT). The reference lists of identified RCTs, personal files and Science Citation Index were searched. No language restrictions were applied. SELECTION CRITERIA: The criteria used to select studies for inclusion in this overview were: 1) DESIGN: RCTs in which administration of IVIG was compared to a control group that received a placebo or no intervention. 2) POPULATION: preterm (< 37 weeks gestational age) and/or LBW (<2500 g) infants. 3) INTERVENTION: IVIG for the prevention of bacterial/fungal infection during initial hospital stay (8 days or longer). (Studies that were primarily designed to assess the effect of IVIG on humoral immune markers were excluded as were studies in which the follow-up period was one week or less). 4) At least one of the following outcomes was reported: sepsis, any serious infection, death from all causes, death from infection, length of hospital stay, intraventricular haemorrhage (IVH), necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD). DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted information for each outcome reported in each study, and one researcher (AO) checked for any discrepancies and pooled the results. Relative risk (RR) and Risk Difference (RD) with 95% confidence intervals (CI) using the fixed effects model are reported. When a statistically significant RD was found the number needed to treat (NNT) was also calculated with 95% CIs. The results include all accepted studies in which the outcome of interest was reported. When statistically significant heterogeneity was found for an outcome, secondary (sensitivity) analyses were performed including only studies of the highest quality. MAIN RESULTS: Fifteen studies met inclusion criteria. These included 5,054 preterm and/or LBW infants and reported on at least one of the outcomes of interest for this systematic review. When all studies were combined there was a statistically significant reduction in sepsis, one or more episodes [RR 0.83 (95% CI 0.72, 0.97); RD -0.028 (95% CI -0.006, -0.051); NNT 36 (95% CI 20, 167)]. There was significant between-study heterogeneity. When, in a sensitivity analysis, the high quality studies were combined, the results remained significant [RR 0.78 (95% CI 0.62, 0.98); RD -0.031(95% CI -0.003, -0.059); NNT 32 (95% CI 17, 333]. For this analysis there was no statistically significant between-study heterogeneity. A statistically significant reduction was also found for any serious infection, one or more episodes, when all studies were combined [RR 0.85 (95% CI 0.75, 0. 95); RD -0.032 (95% CI -0.010, -0.054,); NNT 31 (95% CI 19, 100). There was statistically significant between-study heterogeneity. When, in a sensitivity analysis, the high quality studies were combined the results remained statistically significant [RR 0.80 (95% CI

Cross Infection↗

PubMedDate not supplied

Winning the run for the money. Knowing the art of grantsmanship puts administrators on the inside track.

As more administrators turn to foundations and other funding agencies for money to buy needed technologies or services, the competition for those funds is heating up. Success in tapping those resources requires knowing the ins and outs of grantsmanship. In addition to providing a library of materials on major foundations and philanthropists, the grants office should function as a clearinghouse of data relating to what the facility needs and what has the highest priority among administrators, medical staff, and operations directors. This will enable the grants officer to match needs to opportunities. Although the project originator and the grants officer do most of the work in preparing a proposal, the process should be a team effort. In general, grants come in three basic categories: private foundation grants, corporate foundation grants, and government grants. Private foundation grants do not require a lot of preparation: minimal paperwork and little or no red tape. In an area with a lot of corporations, corporate foundation grants are obvious places to start. Government grants are major projects that should be attempted only by those willing to spend a lot of time shuffling paperwork and untangling red tape.

Documentation↗

PubMed2002

Physician staffing patterns and clinical outcomes in critically ill patients: a systematic review.

CONTEXT: Intensive care unit (ICU) physician staffing varies widely, and its association with patient outcomes remains unclear. OBJECTIVE: To evaluate the association between ICU physician staffing and patient outcomes. DATA SOURCES: We searched MEDLINE (January 1, 1965, through September 30, 2001) for the following medical subject heading (MeSH) terms: intensive care units, ICU, health resources/utilization, hospitalization, medical staff, hospital organization and administration, personnel staffing and scheduling, length of stay, and LOS. We also used the following text words: staffing, intensivist, critical, care, and specialist. To identify observational studies, we added the MeSH terms case-control study and retrospective study. Although we searched for non-English-language citations, we reviewed only English-language articles. We also searched EMBASE, HealthStar (Health Services, Technology, Administration, and Research), and HSRPROJ (Health Services Research Projects in Progress) via Internet Grateful Med and The Cochrane Library and hand searched abstract proceedings from intensive care national scientific meetings (January 1, 1994, through December 31, 2001). STUDY SELECTION: We selected randomized and observational controlled trials of critically ill adults or children. Studies examined ICU attending physician staffing strategies and the outcomes of hospital and ICU mortality and length of stay (LOS). Studies were selected and critiqued by 2 reviewers. We reviewed 2590 abstracts and identified 26 relevant observational studies (of which 1 included 2 comparisons), resulting in 27 comparisons of alternative staffing strategies. Twenty studies focused on a single ICU. DATA SYNTHESIS: We grouped ICU physician staffing into low-intensity (no intensivist or elective intensivist consultation) or high-intensity (mandatory intensivist consultation or closed ICU [all care directed by intensivist]) groups. High-intensity staffing was associated with lower hospital mortality in 16 of 17 studies (94%) and with a pooled estimate of the relative risk for hospital mortality of 0.71 (95% confidence interval [CI], 0.62-0.82). High-intensity staffing was associated with a lower ICU mortality in 14 of 15 studies (93%) and with a pooled estimate of the relative risk for ICU mortality of 0.61 (95% CI, 0.50-0.75). High-intensity staffing reduced hospital LOS in 10 of 13 studies and reduced ICU LOS in 14 of 18 studies without case-mix adjustment. High-intensity staffing was associated with reduced hospital LOS in 2 of 4 studies and ICU LOS in both studies that adjusted for case mix. No study found increased LOS with high-intensity staffing after case-mix adjustment. CONCLUSIONS: High-intensity vs low-intensity ICU physician staffing is associated with reduced hospital and ICU mortality and hospital and ICU LOS.

Adult↗

PubMed2003

Recent advances in physiological and pathological significance of tryptophan-NAD+ metabolites: lessons from insulin-producing pancreatic beta-cells.

In the early 1980s we found that streptozotocin and alloxan, typical diabetogenic agents, induce pancreatic beta-cell DNA strand breaks through the formation of free radicals. The breaks induce DNA repair involving the activation of poly(ADP-ribose) polymerase (PARP), which uses NAD+ as a substrate. As a result, the intracellular levels of NAD+ fall dramatically. The fall in NAD+ inhibits cellular functions including insulin synthesis and secretion, and thus the beta-cell ultimately dies. We subsequently proposed that maintenance of the NAD+ level is essential for the synthesis and secretion of insulin, and presented a unifying model for beta-cell damage and its prevention (The Okamoto model), in which PARP activation plays an essential role. Recently, the model was reconfirmed by experiments using PARP knockout mice and has been recognized as providing the basis for necrotic death of various cells and tissues. In 1993, we found that cyclic ADP-ribose (cADPR), a metabolite of NAD+, is a second messenger for intracellular Ca2+ mobilization for insulin secretion by glucose, and proposed a novel mechanism of insulin secretion, the CD38-cADPR signal system. Recently, various physiological phenomena from animal to plant cells become understandable in terms of this signal system. In 1984, we demonstrated that the administration of PARP inhibitors to 90% depancreatized rats induces islet regeneration. From the regenerating islet-derived cDNA library we found a novel beta-cell growth factor gene, Reg (Regenerating Gene), and elucidated the mechanism of Reg gene expression in beta-cells, in which PARP acts as a transcription factor for Reg gene expression. PARP bound to the cis-element of Reg promoter and formed the active transcriptional DNA/protein complex. The complex formation was inhibited depending on the autopoly(ADP-ribosyl)ation of PARP in the complex. Thus, PARP inhibitors enhance and stabilize the complex formation for Reg gene transcription. Reg protein acts as an autocrine/paracrine growth factor to induce beta-cell replication via the Reg receptor and ameliorates experimental diabetes.

ADP-ribosyl Cyclase↗

PubMed2001

Combinatorial lead optimization of a neuropeptide FF antagonist.

The tripeptide Pro-Gln-Arg-NH2, derivatized at the secondary amino group of the proline residue with 5-(dimethylamino)-1-naphthalenesulfonyl (dansyl-PQR-NH2), antagonizes the central anti-opioid action of neuropeptide FF in animals after systemic administration and, therefore, is a therapeutic lead to treat opiate withdrawal. For a combinatorial optimization to improve potency, libraries focused on the possible replacement of the proline and glutamine residues of this lead compound were obtained by a solid-phase split-and-mix method using coded amino acids (excluding cysteine) as building blocks. After screening for competitive binding against a radioiodinated neuropeptide FF analogue, 5-(dimethylamino)-1-naphthalenesulfonyl-Gly-Ser-Arg-NH2 (dansyl-GSR-NH2) has emerged as one of the compounds in the library with high affinity to the NPFF receptor and even with a moderate increase compared to dansyl-PQR-NH2 in its predicted ability to penetrate the central nervous system.

Animals↗