Colony-stimulating factors for chemotherapy-induced febrile neutropenia: a meta-analysis of randomized controlled trials.

PURPOSE: Current treatment for febrile neutropenia (FN) includes hospitalization for evaluation, empiric broad-spectrum antibiotics, and other supportive care. Clinical trials have reported conflicting results when studying whether the colony-stimulating factors (CSFs) improve outcomes in patients with FN. This Cochrane Collaboration review was undertaken to further evaluate the safety and efficacy of the CSFs in patients with FN. METHODS: An exhaustive literature search was undertaken including major electronic databases (CANCERLIT, EMBASE, LILACS, MEDLINE, SCI, and the Cochrane Controlled Trials Register). All randomized controlled trials that compare CSFs plus antibiotics versus antibiotics alone for the treatment of established FN in adults and children were sought. A meta-analysis of the selected studies was performed. RESULTS: More than 8,000 references were screened, with 13 studies meeting eligibility criteria for inclusion. The overall mortality was not influenced significantly by the use of CSF (odds ratio [OR] = 0.68; 95% CI, 0.43 to 1.08; P = .1). A marginally significant result was obtained for the use of CSF in reducing infection-related mortality (OR = 0.51; 95% CI, 0.26 to 1.00; P = .05). Patients treated with CSFs had a shorter length of hospitalization (hazard ratio [HR] = 0.63; 95% CI, 0.49 to 0.82; P = .0006) and a shorter time to neutrophil recovery (HR = 0.32; 95% CI, 0.23 to 0.46; P < .00001). CONCLUSION: The use of the CSFs in patients with established FN caused by cancer chemotherapy reduces the amount of time spent in hospital and the neutrophil recovery period. The possible influence of the CSFs on infection-related mortality requires further investigation.     

Anatomical Course of the Superficial Branch of the Radial Nerve and Clinical Significance for Surgical Approaches in the Distal Forearm

Abstract 10 embalmed cadaver forearms and wrists were dissected to determine the anatomical course of the superficial branch of the radial nerve in the distal forearm. The superficial radial nerve bifurcated in two branches at a mean of 54,7 mm proximal to the radial styloid. From the styloid process of the radius, the mean distance to the closest dorsal branch of the superficial radial nerve was 3,5 mm and the mean distance to the closest volar branch was 9,8 mm. The mean distance between the closest branch of the superficial radial nerve and Lister?s tubercle was 16,4 mm. The crossing point between the nerve and the cephalic vein was located at a mean of 54,3 mm proximal to the styloid process. At the level of styloid process the mean distance between the closest dorsal branch of the superficial radial nerve and the first dorsal compartment was 15,2 mm and between the closest volar branch and the first dorsal compartment 4,4 mm. Detailed knowledge of anatomic characteristics of the superficial branch of the radial nerve may help prevent injury during operations and treat traumatic lesions of the nerve. Because of great variations in the course of the superficial radial nerve we could not define an absolute safe zone for surgical procedures on the distal forearm. Iatrogenic lesions of the superficial radial nerve are described complications of percutaneous procedures. Therefore open surgical approaches are recommended. Daniela Klitscher and Lars Peter Müller contributed equally to this work.     

Regulation of Basal and Nursing-Induced Secretion of Growth Hormone in the Neonatal Rat: The Involvement of Serotonergic, Muscarinic Cholinergic, Alpha2-Adrenergic, Somatostatin and Growth Hormone-Releasing Hormone Systems

Various neural factors are involved in the suckling-induced increase in serum growth hormone (GH) levels in neonatal rats, and, in the present study the serotonergic, cholinergic, somatostatin and GH-releasing hormone (GHRH) systems were investigated. The serotonin (5-HT) precursor 5-hydroxy-L-tryptophan (5-HTP) and the 5-HT receptor agonist quipazine maleate stimulated serum GH levels in 2-day-old rat pups separated from their mothers for 6 h. The increase in serum GH during suckling was further elevated by 5-HTP. The 5-HT antagonist cyproheptadine decreased serum GH levels in separated 2-day-old pups, and although it reduced the amplitude of the suckling-induced increase in serum GH concentration, it did not alter the increase in serum GH on a percentage basis. The effect of the cholinergic muscarinic antagonist atropine sulfate (ATR) was similar to that of cyproheptadine. Moreover, in separated pups, ATR prevented the increase in serum GH induced by 5-HTP. In contrast with 2-day-old pups, ATR completely eliminated the suckling-induced release of GH in 10-day-old rats. However, ATR failed to prevent GH release induced by the α₂-adrenergic agonist clonidine HCI in 10-day-old male pups. While thyrotropin-releasing hormone increased serum GH levels, rat GHRH failed to alter serum GH levels either in separated or in suckled 2-day-old rat pups. Immunoneutralization for rat GHRH eliminated the increase in serum GH induced by clonidine HCI in 10-day-old pups, but (on a percentage basis) failed to prevent the GH-increasing effect of suckling in 2-day-old pups. While somatostatin failed to significantly decrease serum GH in separated 2-day-old pups, it effectively decreased serum GH levels in 2-day-old pups which were suckled. Cysteamine, which depletes hypothalamic somatostatin, increased serum GH in separated 2-day-old pups, and further increased the suckling-induced levels of serum GH. Cysteamine partially prevented the GH-decreasing effect of ATR. The present findings suggest that 1) the serotonergic and cholinergic systems are involved in the regulation of GH secretion as early as day 2 postpartum; 2) the serotonergic and cholinergic systems modulate the basal, and do not modulate the suckling-induced levels of serum GH; 3) the serotonergic system may exert its stimulatory influence on GH secretion only in the presence of a functional muscarinic cholinergic system; 4) the cholinergic system, at least in part, stimulates GH secretion via a cysteamine-sensitive system (probably by inhibiting somatostatin); 5) the cholinergic system is not functionally coupled with the α₂-adrenergic system, which stimulates GH secretion via rat GHRH; 6) since in 10-day-old pups clonidine HCI was effective only in males, while suckling was effective in both sexes, the α₂-adrenergic system is not involved in the suckling-induced increase of serum GH; and finally 7) neither somatostatin nor rat GHRH seem to be involved in the suckling-induced changes in serum GH. The findings are consistent with the hypothesis that the high circulating GH levels in the neonatal rat are due to alternative GH-releasing factors, perhaps thyrotropin-releasing hormone or γ-aminobutyric acid. The neurohumoral mediator of the suckling-induced GH release in neonatal rats remains to be identified.     

Implementing nursing practice guidelines: a complex undertaking.

Clinical practice guidelines have been proposed to significantly reduce the gap between available scientific evidence and clinical practice. Evidence-based guidelines are also being produced at an ever-increasing pace. However, guidelines do not implement themselves, and the research to support implementation does not provide straightforward answers. What works in one setting does not necessarily work in another. In short, guideline implementation and change of practice is complex and messy. The purpose of this article is to discuss the implementation of clinical practice guidelines using the Promoting Action on Research Implementation in Health Services framework. More specifically, 3 key components are highlighted: (1) the evidence base for guideline recommendations, (2) the clinical context where guidelines are to be implemented, and (3) the nature of facilitation needed to ensure a successful change process. An overview of the literature in the field is provided, and the authors' experiences are shared, and a few recommendations are tentatively provided.     

Reduction of Immunosuppression for Transplant-Associated Skin Cancer: Rationale and Evidence of Efficacy

BACKGROUND: Solid organ transplant recipients may develop numerous or life-threatening skin cancers. In addition to aggressive standard treatment of skin cancer, reduction of immunosuppression has been considered an adjuvant therapeutic strategy, albeit without direct proof of efficacy. OBJECTIVE: To review the rationale for and evidence supporting the efficacy of reduction of immunosuppression for severe skin cancer in transplant recipients. METHODS: Review of the literature regarding direct and indirect evidence on reduction of immunosuppression for transplant-associated skin cancer. RESULTS: Although there are no randomized controlled trials of reduction of immunosuppression as a therapeutic intervention for transplant patients with skin cancer, multiple lines of evidence suggest that this strategy may be an effective adjuvant therapy. A randomized trial has demonstrated a lower incidence of skin cancer in transplant recipients after reduction of immunosuppression, albeit in a cohort not previously affected by skin cancer. Case series of reduction or cessation of immunosuppression demonstrate a lower incidence of skin cancer or improved outcomes of preexisting skin cancer. Lower overall immunosuppression is associated with a lower incidence of skin cancer. Multiple cancers affecting the skin have been shown to regress with reduction of immunosuppression. CONCLUSIONS: Reduction of immunosuppression may be an effective adjuvant therapeutic strategy when confronting severe transplant-associated skin cancer. The risks of reduction of immunosuppression must be better defined, and randomized trials of this strategy are necessary.     

药物动力学入门(三)

重复给药许多药物不仅投药一次。病人在接受药物治疗时,通常是经多次的药物应用。这样每一剂量给予的次数和多少则称为给药方案。通过给药方案的调整,则可以显著地改变药物治疗的效果。口服给药如果口次剂量每次给药的间隔相当长,则由每一次剂量所给的药物已几乎完全消除,所以这些分次给药的行为相互将无何影响,如图33所示。     

Studies of the human oropharyngeal airspaces using magnetic resonance imaging IV--the oropharyngeal retention effect for four inhalation delivery systems.

Magnetic resonance imaging (MRI) of the oropharyngeal region from 20 adult volunteers using four model inhalation devices (varying mouthpiece diameters, airflow resistances) and tidal breathing was carried out. Statistical analysis (convex hull method) selected 12 scans from 80 data sets representing the extremes of all dimensions in the population. Twelve physical mouth-throat models were made by stereolithography using the exact scan data. The aim was to produce models with varying dimensions to span the adult population, and to investigate if oropharyngeal dimensions affected throat retention for different delivery systems. In an in vitro analysis, the models were used to determine the retention effect of the oropharyngeal airspaces when drug aerosols were administered from four inhalation delivery systems: a pressurised metered dose inhaler (pMDI), two different dry powder inhalers (DPIs A and B), and a nebulizer. The aims of this work were to determine the key parameters governing mouth-throat retention and whether retention was dependent on the delivery system used. Characterizing the throat models by measuring 51 different dimensional variables enabled determination of the most influential variables for dose retention for each inhalation delivery system. Throat model retention was found to be dependent on the delivery system (pMDI approximately DPI(A) > DPI(B) > Neb.). The most influential variable was the total throat model volume. Throat models representing high, median, and low oropharyngeal filtration in healthy adults have been identified.     

Serum fractions and related agonists with calcium-mobilizing activity in the bovine growth plate chondrocyte

Longitudinal growth of bone involves a complex sequence of cellular events in the cartilaginous epiphysis. Whole blood serum has been shown previously to be a potent stimulus to the cells of the growth plate, as demonstrated by its ability to activate the inositol phosphate-calcium second messenger system resulting in a rise in intracellular Ca²⁺. By manipulating the preparation of serum to functionally separate it into its constituent parts, we have shown that the processes of platelet lysis and activation of the clotting cascade are responsible for the generation of factors that stimulate this signaling mechanism in isolated bovine growth plate chondrocytes. Through a subsequent trial of bioactive agents generated in these processes, we identified and partially characterized several novel agonists of growth plate chondrocytes: adenosine triphosphate and adenosine diphosphate, the purine energy substrates, and bradykinin, the bioactive peptide generated in a side reaction of the clotting cascade, each induces a rise in intracellular Ca²⁺ via release from intracellular ion stores. Additionally, the three distinct isoforms of platelet-derived growth factor (AA, AB and BB), also released on platelet lysis, were compared with respect to their ability to stimulate the inositol phosphate-calcium second messenger system in growth plate chondrocytes.