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PubMed2002

The contributions of library and information services to hospitals and academic health sciences centers: a preliminary taxonomy.

OBJECTIVES: This article presents a taxonomy of the contributions of library and information services (LIS) in hospitals and academic health sciences centers. The taxonomy emerges from a study with three objectives: to articulate the value of LIS for hospitals and academic health sciences centers in terms of contributions to organizational missions and goals, to identify measures and measurable surrogates associated with each LIS contribution, and to document best practices for communicating the value of LIS to institutional administrators. METHODS: The preliminary taxonomy of LIS contributions in hospitals and academic health sciences centers is based on a review of the literature, twelve semi-structured interviews with LIS directors and institutional administrators, and a focus group of administrators from five academic, teaching, and nonteaching hospitals. RESULTS: Derived from the balanced scorecard approach, the taxonomy of LIS contributions is organized on the basis of five mission-level concepts and fifteen organizational goals. LIS contributions are included only if they have measurable surrogates. CONCLUSIONS: The taxonomy of LIS contributions offers a framework for the collection of both quantitative and qualitative data in support of communicating the value of LIS in hospitals and academic health sciences centers.

Academic Medical Centers↗
PubMed2000

Single dose oxycodone and oxycodone plus paracetamol (acetominophen) for acute postoperative pain.

BACKGROUND: Oxycodone is a strong opioid agonist which is useful for the management of severe pain. It is becoming increasingly important to assess the relative efficacy and harm caused by different treatments. This can be determined when an analgesic is compared with control under similar clinical circumstances. OBJECTIVES: To quantitatively assess the analgesic efficacy and adverse effects of single-dose oxycodone and oxycodone plus paracetamol in randomised trials in acute postoperative pain. SEARCH STRATEGY: Published reports were identified from Medline, Biological Abstracts, Embase, the Cochrane Library and the Oxford Pain Relief Database. Additional studies were identified from the reference lists of retrieved reports. SELECTION CRITERIA: The inclusion criteria were: full journal publication, clinical trial, random allocation of adult patients to treatment groups, double blind design, moderate to severe baseline pain, postoperative administration of study drugs, treatment arms which included oxycodone or oxycodone plus paracetamol and placebo (or active control for which comparable efficacy data exist), and oral, intramuscular or intravenous administration of study drugs. DATA COLLECTION AND ANALYSIS: Summed pain intensity and pain relief data over 4-6 hours were extracted and converted into dichotomous information yielding the number of patients obtaining at least 50% pain relief. Estimates of relative benefit and number-needed-to-treat were calculated. Single-dose adverse effect data were collected. MAIN RESULTS: Seventy-seven reports were identified. Seven reports met the inclusion criteria; all assessed oral oxycodone. For efficacy, a significant benefit of active drug over placebo was shown for all doses of oxycodone and oxycodone plus paracetamol, except oxycodone 5 mg. For adverse effects, the number of patients reporting adverse effects was extracted for each dose of active drug versus placebo. When these data were pooled for the individual doses significantly more adverse effects with active drug than with placebo were shown for all doses, except oxycodone 5 mg and its combination with paracetamol 325 mg. This was also shown for drowsiness/somnolence. Significantly more nausea, vomiting and dizziness/lightheadedness were reported with oxycodone 10 mg plus paracetamol (650 mg and 1000 mg) than with placebo. REVIEWER'S CONCLUSIONS: Single-dose oral oxycodone, with or without paracetamol, appears to be of comparable efficacy to intramuscular morphine and non-steroidal anti-inflammatory drugs. Central nervous system adverse effects were common.

Acetaminophen↗
PubMed1997

Recombinant advanced glycation end product receptor pharmacokinetics in normal and diabetic rats.

Vascular dysfunction in patients with diabetes mellitus is related to advanced glycation end product (AGE) formation. We previously showed that AGEs produce an increase in vascular permeability and generated an oxidant stress after binding to the receptor (RAGE) present on endothelium. RAGE, a 35-kDa protein that belongs to the immunoglobulin superfamily, has been cloned from a rat lung cDNA library, and recombinant rat soluble RAGE (rR-RAGE) has been produced in insect cells. The sequence of RAGE is highly conserved between human and rat. We studied the biological effect of rR-RAGE and pharmacokinetics of 125I-rR-RAGE after intravenous or intraperitoneal administration in normal and streptozotocin-induced diabetic rats. rR-RAGE prevented albumin or inulin transfer through a bovine aortic endothelial cell monolayer, restored the hyperpermeability observed in diabetic rats or induced in normal rats by diabetic rat red blood cells, and corrected the reactive oxygen intermediate production after intravenous or intraperitoneal administration. After intravenous injection of 125I-rR-RAGE, the distribution half-life was longer (p < or = 0.01) in diabetic (0.15 and 4.01 hr) than in normal (0.02 and 0.21 hr) rats, as was the case for the elimination half-lives (diabetic, 57.17 hr; normal, 26.02 hr; p < or = 0.01). Distribution volume was higher in diabetic than in normal rats (6.94 and 3.24 liter/kg, respectively; p = 0.049). Our study showed that rR-RAGE was biologically active in vivo and slowly cleared, which suggests it could be considered as a potential therapy.

Amino Acid Sequence↗
PubMed2004

Efficacy and tolerability of the new antiepileptic drugs I: treatment of new onset epilepsy [RETIRED]: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

OBJECTIVE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide-reviewed in the order in which these agents received approval by the US Food and Drug Administration) in the treatment of children and adults with newly diagnosed partial and generalized epilepsies. METHODS: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until September 2002, with selected manual searches up until 2003. RESULTS: There is evidence either from comparative or dose-controlled trials that gabapentin, lamotrigine, topiramate, and oxcarbazepine have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. There is also evidence that lamotrigine is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking. CONCLUSIONS: The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes where more evidence is necessary.

Acetates↗
PubMed2001

A Brugia malayi homolog of macrophage migration inhibitory factor reveals an important link between macrophages and eosinophil recruitment during nematode infection.

Infections with the helminth parasite Brugia malayi share many key features with Th2-mediated allergic diseases, including recruitment of eosinophils. We have investigated the dynamics of inflammatory cell recruitment under type 2 cytokine conditions in mice infected with B. malayi. Among the cells recruited to the site of infection is a novel population of "alternatively activated" macrophages that ablate cell proliferation and enhance Th2 differentiation. By profiling gene expression in this macrophage population, we found a dramatic up-regulation of a recently described eosinophil chemotactic factor, eosinophil chemotactic factor-L/Ym1, representing over 9% of clones randomly selected from a cDNA library. Because B. malayi is known to secrete homologs (Bm macrophage migration inhibitory factor (MIF)-1 and -2) of the human cytokine MIF, we chose to investigate the role this cytokine mimic may play in the development of the novel macrophage phenotype observed during infection. Strikingly, administration of soluble recombinant Bm-MIF-1 was able to reproduce the effects of live parasites, leading both to the up-regulation of Ym1 by macrophages and a marked recruitment of eosinophils in vivo. Because activity of Bm-MIF-1 is dependent upon an amino-terminal proline, this residue was mutated to glycine; the resultant recombinant (Bm-MIF-1G) was unable to induce Ym1 transcription in macrophages or to mediate the recruitment of eosinophils. These data suggest that macrophages may provide a crucial link between helminth parasites, their active cytokine mimics, and the recruitment of eosinophils in infection.

Animals↗
PubMed1999

Aloe vera: a systematic review of its clinical effectiveness.

BACKGROUND: The use of aloe vera is being promoted for a large variety of conditions. Often general practitioners seem to know less than their patients about its alleged benefits. AIM: To define the clinical effectiveness of aloe vera, a popular herbal remedy in the United Kingdom. METHOD: Four independent literature searches were conducted in MEDLINE, EMBASE, Biosis, and the Cochrane Library. Only controlled clinical trials (on any indication) were included. There were no restrictions on the language of publication. All trials were read by both authors and data were extracted in a standardized, pre-defined manner. RESULTS: Ten studies were located. They suggest that oral administration of aloe vera might be a useful adjunct for lowering blood glucose in diabetic patients as well as for reducing blood lipid levels in patients with hyperlipidaemia. Topical application of aloe vera is not an effective preventative for radiation-induced injuries. It might be effective for genital herpes and psoriasis. Whether it promotes wound healing is unclear. There are major caveats associated with all of these statements. CONCLUSION: Even though there are some promising results, clinical effectiveness of oral or topical aloe vera is not sufficiently defined at present.

Administration, Oral↗
PubMed1999

The Reg gene family and Reg proteins: with special attention to the regeneration of pancreatic beta-cells.

Pancreatic beta-cells of the islets of Langerhans are the only cells that produce insulin in humans, as well as in most animals, but they have been thought to have a limited capacity for regeneration, which is a predisposing factor for the development of diabetes mellitus. Strategies for influencing the replication and growth of the beta-cell mass are therefore important for the prevention and/or treatment of diabetes. We have established a model for islet regeneration in 90% depancreatized rats by the administration of poly(ADP-ribose) synthetase inhibitors such as nicotinamide. The regenerating islets in the remaining pancreas of poly(ADP-ribose) synthetase inhibitor-treated rats were markedly enlarged and consisted largely of insulin-producing beta-cells, preventing the development of diabetes mellitus that would otherwise be caused by the 90% pancreatectomy. In screening the regenerating islet-derived cDNA library, we found a novel gene and named it Reg (i.e., regenerating gene). The rate Reg cDNA had a single open reading frame that encoded a 165-amino acid protein with a 21-amino acid signal peptide. We also isolated the human REG cDNA which encoded a 166-amino acid protein with a 22-amino acid signal peptide. The amino acid sequence of human REG protein has 68% homology to that of rat Reg protein. Recombinant rat Reg protein without the signal peptide, produced in yeast, stimulated beta-cell replication and increased the beta-cell mass in the residual pancreas of 90% depancreatized rats, ameliorating the surgical diabetes. Recombinant human REG protein also induced an expansion of the beta-cell mass in non-obese diabetic (NOD) mice, resulting in the amelioration of diabetes. These results, as well as several other lines of evidence, indicate that Reg protein is a growth factor for pancreatic beta-cells and also suggest that the administration of Reg protein and/or activation of the Reg gene can be used as a potential therapeutic approach for diabetes mellitus. We have further isolated several Reg and Reg-related genes from human, rat and mouse, and revealed that they constitute a multigene family, the Reg gene family. Based on the primary structures of proteins encoded by the Reg gene family, we have grouped the members of the family into three subclasses, type I, II, and III. Type I Reg (Reg I) encodes a beta-cell growth factor, Reg I protein, as mentioned above. Some of the type III Reg (Reg III) have recently been suggested to play roles in the regeneration of cells other than pancreatic beta-cells, such as neuronal cells and epithelial cells in the alimentary tract.

Amino Acid Sequence↗
PubMed2001

Antibiotics versus placebo for prevention of postoperative infection after appendicectomy.

BACKGROUND: Appendicitis is the most common cause of acute abdominal pain requiring surgical intervention. The cause of appendicitis is unclear and the mechanism of pathogenesis continues to be debated. Despite improved asepsis and surgical techniques, postoperative complications, such as wound infection and intraabdominal abscess, still account for a significant morbidity. Several studies implicate that postoperative infections are reduced by administration of antimicrobial regimes. OBJECTIVES: The objective of this review is to compare the use of antibiotics with placebo or no treatment in patients undergoing appendectomy. Will these patients benefit from antimicrobial prophylaxis? The outcomes are described according to the nature of the appendix, as either simple appendicitis (including the non-infectious stage) and complicated appendicitis. This review do not attempt to compare the effect of different regimens, a clinical question that is addressed in another review undertaken by this Group (CCCG). SEARCH STRATEGY: We searched The Cochrane Controlled Trials Register (Cochrane Library 2000 issue 4), Medline (January 1966 to September 2000), Embase and the Cochrane Colorectal Cancer Group specialised register (September 2000). In addition we manually searched the reference lists of the primary identified trials. SELECTION CRITERIA: Randomised Controlled Trials (RCT) and Controlled Clinical Trials (CCT) in which any antibiotic regime were compared to placebo in patients suspected of having appendicitis undergoing appendectomy were evaluated. Both studies on children and adults were reviewed. The outcome measures of the studies were either wound infection, intraabdominal abscess, length of stay in hospital or mortality. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed, recorded and cross-checked by to reviewers. MAIN RESULTS: Forty-four studies including 9298 patients were included in this review. The overall result is that use of antibiotics is superior to placebo for the outcome wound infection and intraabdominal abscess, with no apparent difference in the nature of the removed appendix. Studies exclusively on children and studies examining topical application reported results in favour to the above although the results were not significant. REVIEWER'S CONCLUSIONS: Antibiotic prophylaxis is effective in the prevention of postoperative complications in appendectomised patients, whether the administration are given pre-, per- and post-operatively and could be considered for routine in emergency appendectomies.

Abdominal Abscess↗
PubMed2005

Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency.

BACKGROUND: Vitamin B12 deficiency is common and rises with age. Most people with vitamin B12 deficiency are treated in primary care with intramuscular vitamin B12 which is a considerable source of work for health care professionals. Several case control and case series studies have reported equal efficacy of oral administration of vitamin B12 but it is rarely prescribed in this form, other than in Sweden and Canada. Doctors may not be prescribing oral formulations because they are unaware of this option or have concerns regarding effectiveness. OBJECTIVES: To assess the effectiveness of oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. SEARCH STRATEGY: Searches were undertaken of The Cochrane Library, MEDLINE, EMBASE and Lilacs in early 2005. The bibliographies of all relevant papers identified using this strategy were searched. In addition we contacted authors of relevant identified studies and Vitamin B12 research and pharmaceutical companies to enquire about other published or unpublished studies and ongoing trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) examining the use of oral or intramuscular vitamin B12 to treat vitamin B12 deficiency. DATA COLLECTION AND ANALYSIS: All abstracts or titles identified by the electronic searches were independently scrutinised by two reviewers. When a difference between reviewers arose, we obtained and reviewed a hard copy of the papers and made decisions by consensus. We obtained a copy of all pre-selected papers and two researchers independently extracted the data from these studies using piloted data extraction forms. The whole group checked whether inclusion and exclusion criteria were met, and disagreement was decided by consensus. The methodological quality of the included studies was independently assessed by two researchers and disagreements were brought back to the whole group and resolved by consensus. MAIN RESULTS: Two RCT's comparing oral with intramuscular administration of vitamin B12 met our inclusion criteria. The trials recruited a total of 108 participants and followed up 93 of these from 90 days to four months. High oral doses of B12 (1000 mcg and 2000 mcg) were as effective as intramuscular administration in achieving haematological and neurological responses. AUTHORS' CONCLUSIONS: The evidence derived from these limited studies suggests that 2000 mcg doses of oral vitamin B12 daily and 1000 mcg doses initially daily and thereafter weekly and then monthly may be as effective as intramuscular administration in obtaining short term haematological and neurological responses in vitamin B12 deficient patients.

Administration, Oral↗
PubMed2004

Prophylactic oral antifungal agents to prevent systemic candida infection in preterm infants.

BACKGROUND: Systemic fungal infection has increased in prevalence in neonatal intensive care units (NICU) caring for very low birth weight infants. It is associated with a prolonged stay and an increase in morbidity and mortality. An assessment of the use of oral prophylactic antifungals to prevent systemic infection is needed. OBJECTIVES: To assess whether the prophylactic administration of oral antifungal agents to very preterm infants reduces the occurrence of systemic fungal infection. SEARCH STRATEGY: The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. Searches were carried out up to July 2003 on the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 2, 2003), MEDLINE from 1966, EMBASE from 1980, CINAHL from 1992. Abstracts from SPR (1993 - 2003) and ESPR (1995 to 2002) were hand searched. SELECTION CRITERIA: Randomized and quasi randomized controlled trials in very low birth weight or very preterm infants in which an oral antifungal agent was compared with placebo or no treatment or another oral antifungal agent DATA COLLECTION AND ANALYSIS: Data were extracted using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of the trial quality and data extraction undertaken by each author. Results were reported using relative risk (RR) and risk difference (RD) and weighted mean difference (WMD). 95% confidence intervals were reported. MAIN RESULTS: We identified three eligible trials, one comparing nystatin with no treatment (67 infants), one comparing miconazole with placebo (600 infants), and one comparing nystatin with fluconazole (21 infants). As the two trials comparing nystatin or miconazole with placebo or no treatment were clinically quite different, meta-analysis was not performed. In the trial of nystatin versus no treatment, systemic fungal infection was significantly reduced [RR 0.19 (0.04,0.78)] in the group treated with nystatin. In the study comparing miconazole with placebo there was no significant effect on systemic fungal infection [RR 1.32 (0.46,3.75)]. Neither study found a significant effect on mortality, and there was no significant difference in the mean number of days infants received ventilation or stayed in the neonatal intensive care unit. In the small trial comparing oral fluconazole with nystatin, no significant difference in systemic fungal infection [RR 0.17 (0.01, 2.84)] or mortality [RR 0.17 (0.01, 2.84)] was reported. Adverse drug reactions were not reported in any study. REVIEWER'S CONCLUSIONS: There is insufficient evidence to support the use of prophylactic oral antifungal agents in very low birth weight infants in the neonatal intensive care unit. Randomised controlled trials in current neonatal practice settings are needed, comparing oral antifungal agents with placebo and with each other and including an assessment of side effects, in order to determine whether oral antifungal agents have a role in preventing systemic fungal infections in preterm infants.

Administration, Oral↗
PubMed2006

Opioid antagonists under heavy sedation or anaesthesia for opioid withdrawal.

BACKGROUND: Withdrawal (detoxification) is necessary prior to drug-free treatment. It may also represent the end point of long-term opioid replacement treatment such as methadone maintenance. The availability of managed withdrawal is essential to an effective treatment system. OBJECTIVES: To assess the effectiveness of interventions involving the administration of opioid antagonists to induce opioid withdrawal with concomitant heavy sedation or anaesthesia, in terms of withdrawal signs and symptoms, completion of treatment and adverse effects. SEARCH STRATEGY: We searched the Drugs and Alcohol Group register (October 2003), Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2004), Medline (January 1966 to January 2005), Embase (January 1985 to January 2005), PsycINFO (1967 to January 2005), and Cinahl (1982 to December 2004) and reference lists of studies. SELECTION CRITERIA: Controlled trials comparing antagonist-induced withdrawal under heavy sedation or anaesthesia with another form of treatment, or a different regime of anaesthesia-based antagonist-induced withdrawal. DATA COLLECTION AND ANALYSIS: One reviewer assessed studies for inclusion and undertook data extraction and assessed quality. Inclusion decisions and the overall process were confirmed by consultation between all three reviewers. MAIN RESULTS: Six studies (five randomised controlled trials) involving 834 participants met the inclusion criteria for the review.Antagonist-induced withdrawal is more intense but less prolonged than withdrawal managed with reducing doses of methadone, and doses of naltrexone sufficient for blockade of opioid effects can be established significantly more quickly with antagonist-induced withdrawal than withdrawal managed with clonidine and symptomatic medications. The level of sedation does not affect the intensity and duration of withdrawal, although the duration of anaesthesia may influence withdrawal severity. There is a significantly greater risk of adverse events with heavy, compared to light, sedation (RR 3.21, 95% CI 1.13 to 9.12, P = 0.03) and probably also other forms of detoxification. AUTHORS' CONCLUSIONS: Heavy sedation compared to light sedation does not confer additional benefits in terms of less severe withdrawal or increased rates of commencement on naltrexone maintenance treatment. Given that the adverse events are potentially life-threatening, the value of antagonist-induced withdrawal under heavy sedation or anaesthesia is not supported. The high cost of anaesthesia-based approaches, both in monetary terms and use of scarce intensive care resources, suggest that this form of treatment should not be pursued.

Anesthetics↗
PubMed2003

Erythromycin for the prevention of chronic lung disease in intubated preterm infants at risk for, or colonized or infected with Ureaplasma urealyticum.

BACKGROUND: Controversy exists over whether or not Ureaplasma urealyticum colonization or infection of the respiratory tract contributes to the severity of chronic lung disease (CLD), a major cause of morbidity and mortality in preterm infants. OBJECTIVES: To evaluate the efficacy and safety of prophylactic or therapeutic erythromycin in preventing chronic lung disease in intubated preterm infants with unknown U. urealyticum status or proven positivity. SEARCH STRATEGY: Searches were done of MEDLINE (1966-June 9, 2003), EMBASE (1980-May 5, 2003), The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2002), previous reviews including cross-references, and abstracts of conference proceedings (Pediatric Academic Societies 2000-2003, American Thoracic Society 2001-2003). There were no language restrictions. Expert informants were contacted. SELECTION CRITERIA: Randomized or quasi-randomized studies comparing either prophylactic or therapeutic administration of oral or intravenous erythromycin (regardless of dose and duration) versus no treatment or placebo among intubated preterm infants <37 weeks and <2500 grams with either unknown U. urealyticum status or proven positivity by culture or polymerase chain reaction. DATA COLLECTION AND ANALYSIS: Data were extracted by all of the authors independently and differences were resolved by consensus. Treatment effects for categorical outcomes were expressed as relative risk, with 95% confidence intervals. MAIN RESULTS: Two small controlled studies, both involving intubated babies <30 weeks gestation, were eligible for inclusion. Lyon 1998 tested prophylactic erythromycin in babies whose U. urealyticum status was unknown at the time of initiation of treatment. Jonsson 1998 tested erythromycin in babies known to be culture positive for U. urealyticum. Neither trial showed a statistically significant effect of erythromycin on CLD, death or the combined outcome CLD or death. Because the two studies differed importantly in their design, the results were not combined in meta-analyses. No adverse effects of a 7-10 day course of erythromycin were reported in either study. REVIEWER'S CONCLUSIONS: Current evidence does not demonstrate a reduction in CLD/death when intubated preterm infants are treated with erythromycin prophylactically before U. urealyticum culture/PCR results are known or when Ureaplasma colonized, intubated preterm infants are treated with erythromycin. However, a true benefit could easily have been missed with the small sample sizes in the two eligible studies. The studies were greatly underpowered to detect uncommon adverse effects such as pyloric stenosis. Additional controlled trials are required to determine whether antibiotic therapy of Ureaplasma reduces CLD and/or death in intubated preterm infants.

Anti-Bacterial Agents↗
PubMed1994

Pancreatic beta-cell replication and amelioration of surgical diabetes by Reg protein.

We previously isolated from a rat regenerating islet cDNA library a gene named Reg, which is expressed in regenerating islets but is not expressed in normal islets. Here we examined the effect of rat Reg protein on pancreatic beta-cell replication using both 90% depancreatized rats and isolated islets. The depancreatized rats that received i.p. administration of recombinant rat Reg protein (1 mg/kg per day) for 2 months showed amelioration of the surgical diabetes, as evidenced by a significant decrease in blood glucose with an increased beta-cell mass in the residual pancreas. In isolated rat islets, Reg protein (18-180 nM: 0.3-3 micrograms/ml) significantly increased [3H]thymidine incorporation into the nuclei of beta cells. These results indicate that Reg protein is a growth factor for pancreatic beta cells and also suggest that the administration of Reg protein could be used as another therapeutic approach for diabetes mellitus.

Animals↗
PubMed2005

Novel SRESPHP peptide mediates specific binding to primary medullary thyroid carcinoma after systemic injection.

The efficient and specific introduction of genes into cancer cells in vivo remains a major challenge for current gene therapy modalities. Peptides possess appropriate properties to serve as tumor-targeting agents. Thus, finding new cancer-selective peptides directing gene transfer to neoplastic cells by reducing transduction of normal cells is a central goal for molecular targeting. We have previously reported identification of a peptide (HTFEPGV) that selectively binds to human medullary thyroid carcinoma (MTC)-derived TT cells in vitro and transplanted tumor xenografts in vivo, using phage display. In the present study, we have performed this approach in primary orthotopically growing murine MTCs of RET-C634R transgenic mice as a clinically relevant model for thyroid cancer by intravenous injection of a complex peptide library. Two rounds of screening on primary tumors yielded multiple copies of a phage that displays a cyclic 7-amino acid peptide, SRESPHP, with a 3000-fold increase in titer between rounds 1 and 2. The selected phage showed highly specific binding to the tumor after systemic administration, whereas binding to other organs such as lung, liver, kidney, and heart was reduced up to 90%. After tail vein injection, homing to the tumor was substantially reduced in the presence of synthetic SRESPHP peptide, indicating that tumor phage interaction strictly depends on the displayed peptide. Immunohistochemical analysis of paraffin sections from mouse tissues revealed direct binding of the SRESPHP peptide to MTC tissue. Moreover, this peptide also mediates binding to human MTC cells in vitro and in vivo, suggesting abundant expression of its cognate receptor in murine and human medullary thyroid carcinoma. Because the SRESPHP peptide is also efficiently internalized into MTC cells, it likely provides the basis for a new selective therapy of medullary thyroid carcinoma.

Amino Acid Sequence↗
PubMed1998

DNA vaccines.

DNA vaccination against infectious diseases has created a new field of applied molecular immunology. cDNAs for 'protective' protein epitopes can be inserted into vectors containing strong mammalian promoters for high expression. Here we discuss the mechanisms of DNA vaccination and the successful and sometimes unsuccessful applications of DNA vaccination to protect animals against many different viral, bacterial mycoplasmal, protozoal, and worm infections or infestations. DNA immunization has been used to prevent or inhibit tumor development and to inhibit IgE responses by diverting the immune response from Th2 to Th1 helper cell dominance. Advantages and disadvantages of a variety of routes of administration and methods of immunization discussed include the use of the 'gene gun', the delivery of genes by aerosols, and deliberate induction of injury to muscles prior to injection of DNA to enhance gene expression. Vaccination performed using DNA without knowing beforehand the protective epitopes, using 'expression library immunization', is discussed. While this field is bound to expand rapidly for future clinical applications, we try to point out potential pitfalls as well as advantages of this relatively new technology.

Animals↗
PubMed2000

Intravenous immunoglobulin for suspected or subsequently proven infection in neonates.

BACKGROUND: Congenital and nosocomial infections are important causes of neonatal morbidity and mortality. 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. Theoretically infectious morbidity and morbidity could be reduced by the administration of intravenous immunoglobulin. OBJECTIVES: To assess the effectiveness of intravenous immunoglobulin (IVIG) to reduce mortality/morbidity caused by suspected infection in newborn infants. In secondary analyses to assess the effectiveness of IVIG to reduce mortality/morbidity in those neonates who entered into the studies with suspected infection and who later were confirmed as being infected. SEARCH STRATEGY: Medline, Embase, and Reference Update Databases were searched in November 1997, and the Cochrane Library in July 1998 using the following keywords: immunoglobulin and infant-newborn, and random allocation, or controlled trial, or randomized controlled trial (RCT). The reference lists of identified RCTs and meta-analyses, personal files and Science Citation Index were also searched. No language restrictions were applied. Unpublished data were requested from authors and information has been obtained from one author to date. SELECTION CRITERIA: The criteria used to select studies for inclusion were: 1) DESIGN: RCT (including quasi-randomized trials) 2) Newborn infants (< 28 days old) 3) INTERVENTION: IVIG for treatment of suspected (and in some infants subsequently proved) bacterial/fungal infection compared to placebo or no intervention. Suspected infection was defined as clinical symptoms and signs consistent with infection without isolation of causative organism. Proved infection was defined as: clinical symptoms and signs consistent with infection in association with isolation of causative organism from either blood culture, cerebrospinal fluid culture, urine culture (urine obtained by suprapubic tap) or a normally sterile site (e.g., liver, spleen, meninges, lung) at autopsy. 4) At least one of the following outcomes was reported: mortality during initial hospital stay; length of hospital stay; side effects; psychomotor development/growth at follow up. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted information for the outcomes of interest 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 for dichotomous outcomes and weighted mean difference (WMD) for continuous data. NNT was calculated for outcomes that showed a statistically significant reduction in RD. Data from quasi-randomized trials were excluded in sensitivity analyses. MAIN RESULTS: Study quality was generally poor. Four of 7 identified studies (n = 208), reported on the outcomes of all randomized patients with clinically suspected infection. Mortality was reduced [RR 0.52 (95% CI; 0.28, 0.98), RD -0.102 (95% CI; -0.005, -0.199, NNT 10 (95% CI; 5, 200]. When, in a sensitivity analysis (n = 126), the results from a quasi-randomized trial (n = 82) were excluded, RR and RD remained similar, [RR 0.53 (95% CI; 0.25, 1.15), RD -0.106 (-0.232, 0.021)] but statistical significance was lost. Treatment with IVIG (six trials, n = 234) in cases of subsequently proved infection did not result in a statistically significant reduction in mortality [RR 0.62 (95% CI; 0.34, 1.12, RD -0.074 (95% CI; -0.163, 0. 014)]. Excluding in a sensitivity analysis (n = 199) a quasi-randomized trial (n = 35) changed the results slightly [RR 0. 68 (95% CI; 0.36, 1.29), RD -0.059 (-0.152, 0.035)]. There was no statistically significant between-study

Humans↗
PubMed1996

The Missouri planning grant for the education and training of health sciences librarians.

The planning grant at the School of Library and Informational Science (SLIS) at the University of Missouri has two aims: (a) developing a model curriculum for health sciences librarianship at the master's level and (b) developing materials that can be delivered by alternative instructional methods. To accomplish the first aim, the faculty will investigate the possibility of offering courses in other disciplines, such as health care administration, educational technology, adult education, and medical sociology. In addition, the SLIS faculty will investigate the development of new kinds of placement for the students' practicum experience. To reach the second aim, the SLIS faculty will investigate alternative means of delivering both graduate and continuing education. Three instructional modalities will be evaluated. Some material will be delivered via satellite broadcast, some material will be made available via the World Wide Web and some will be presented in an intensive seminar. The outcome of the planning grant will be two distinct plans. The first will be a plan for the curriculum in health sciences librarianship at the master's level. The second will be a plan for offering instruction through alternative methods, both for graduate education and for continuing education.

Computer Communication Networks↗
PubMed1998

The search for orally active medications through combinatorial chemistry.

The literature of combinatorial chemistry is reviewed with particular attention paid to considerations of absorption, distribution, metabolism and excretion in the design and evaluation of libraries containing drug-like molecules. Published libraries are evaluated in particular for the likelihood that the products would possess oral bioavailability.

Administration, Oral↗