[Systematic review of the implementation and evaluation of Pharmaceutical Care in hospitalised patients(Pharmaceutical Care implementation in hospitalised patients. Systematic review)]. / Revision sistemática sobre la implantación y la evaluación del seguimiento farmacoterapéutico en pacientes hospitalizados.

INTRODUCTION: The persistent morbidity and mortality related to pharmaceutical treatment for hospitalised patients mean that it is necessary to identify scientific criteria for implementing and evaluating Pharmaceutical Care (phC) on the hospital setting. OBJECTIVE: The purpose of the study is to perform a systematic literature review in order to locate, select and analyse studies on implementing and evaluating phC in hospitalised patients. MATERIAL AND METHODS: We searched for articles having to do with clinical pharmacy (CP) and phC published between 1990 and 2006, using a restricted search technique combining all descriptors. The databases we searched were Medline, Embase-Drug & Pharmacology and Cochrane Library. We selected original articles and reviews in English or Spanish describing a phC and clinical pharmacy programme having a participating pharmacist and used in hospitalised patients. RESULTS: We located 66 publications, of which 49 (74.2%) were included and 17 (25.8%) were excluded. We selected 15 (22.7%) on integrating CP and phC in the hospital environment, 18 (27.3%) on implementing phC and 16 (24.2%) relating to evaluating phC programmes. CONCLUSIONS: In the listed studies, pharmacists have managed to incorporate phC programmes in pharmacy divisions' treatment activities. Joining efforts in order to unify CP and phC criteria should be a plan for a common future in this profession. Patients under care should obtain concrete health benefits from phC use, and hospitals should recognise that they create beneficial effects at a reasonable cost.

Yeast carboxypeptidase Y vacuolar targeting signal is defined by four propeptide amino acids.

The amino-terminal propeptide of carboxypeptidase Y (CPY) is necessary and sufficient for targeting this glycoprotein to the vacuole of Saccharomyces cerevisiae. A 16 amino acid stretch of the propeptide was subjected to region-directed mutagenesis using randomized oligonucleotides. Mutations altering any of four contiguous amino acids, Gln-Arg-Pro-Leu, resulted in secretion of the encoded CPY precursor (proCPY), demonstrating that these residues form the core of the vacuolar targeting signal. Cells that simultaneously synthesize both wild-type and sorting-defective forms of proCPY efficiently sort and deliver only the wild-type molecule to the vacuole. These results indicate that the PRC1 missorting mutations are cis-dominant, implying that the mutant forms of proCPY are secreted as a consequence of failing to interact with the sorting apparatus, rather than a general poisoning of the vacuolar protein targeting system.

PEP4 gene of Saccharomyces cerevisiae encodes proteinase A, a vacuolar enzyme required for processing of vacuolar precursors.

The proteinase A structural gene of Saccharomyces cerevisiae was cloned by using an immunological screening procedure that allows detection of yeast cells which are aberrantly secreting vacuolar proteins (J. H. Rothman, C. P. Hunter, L. A. Valls, and T. H. Stevens, Proc. Natl. Acad. Sci. USA, 83:3248-3252, 1986). A second cloned gene was obtained on a multicopy plasmid by complementation of a pep4-3 mutation. The nucleotide sequences of these two genes were determined independently and were found to be identical. The predicted amino acid sequence of the cloned gene suggests that proteinase A is synthesized as a 405-amino-acid precursor which is proteolytically converted to the 329-amino-acid mature enzyme. Proteinase A shows substantial homology to mammalian aspartyl proteases, such as pepsin, renin, and cathepsin D. The similarities may reflect not only analogous functions but also similar processing and intracellular targeting mechanisms for the two proteins. The cloned proteinase A structural gene, even when it is carried on a single-copy plasmid, complements the deficiency in several vacuolar hydrolase activities that is observed in a pep4 mutant. A strain carrying a deletion in the genomic copy of the gene fails to complement a pep4 mutant of the opposite mating type. Genetic linkage data demonstrate that integrated copies of the cloned proteinase A structural gene map to the PEP4 locus. Thus, the PEP4 gene encodes a vacuolar aspartyl protease, proteinase A, that is required for the in vivo processing of a number of vacuolar zymogens.

FDG-PET imaging in hematological malignancies.

The majority of aggressive lymphomas is characterized by an up regulated glycolytic activity, which enables the visualization by F-18 FDG-PET/CT. One-stop hybrid FDG-PET/CT combines the functional and morphologic information, outperforming both, CT and FDG-PET as separate imaging modalities. This has resulted in several recommendations using FDG-PET/CT for staging, restaging, monitoring during therapy, and assessment of treatment response as well as identification of malignant transformation. FDG-PET/CT may obviate the need for a bone marrow biopsy in patients with Hodgkin's lymphoma and diffuse large B cell lymphoma. FDG-PET/CT response assessment is recommended for FDG-avid lymphomas, whereas CT-based response evaluation remains important in lymphomas with low or variable FDG avidity. The treatment induced change in metabolic activity allows for assessment of response after completion of therapy as well as prediction of outcome early during therapy. The five-point scale Deauville Criteria allows the assessment of treatment response based on visual FDG-PET analysis. Although the use of FDG-PET/CT for prediction of therapeutic response is promising it should only be conducted in the context of clinical trials. Surveillance FDG-PET/CT after complete remission is discouraged due to the relative high number of false-positive findings, which in turn may result in further unnecessary investigations. Future directions include the use of new PET tracers such as F-18 fluorothymidine (FLT), a surrogate biomarker of cellular proliferation and Ga-68 CXCR4, a chemokine receptor imaging biomarker as well as innovative digital PET/CT and PET/MRI techniques.

[Infected urachal cyst in adults]. / Quiste uracal infectado en adultos.

A case of infected urachal cyst in a 42 years old women is described. Cystography shows the spontaneous drainage to the bladder through the vesical extremity of the urachus. Review of the Literature is included.

[Drug therapy follow-up in patients admitted to a Surgery Department]. / Seguimiento del tratamiento farmacológico en pacientes ingresados en un Servicio de Cirugía.

INTRODUCTION: Patients admitted to surgery departments receive multiple drugs before, during and after surgical procedures. Anti-infectious therapy, anesthetics, anti-embolic agents, and analgesics stand out amongst others. Our objective was to implement pharmacotherapeutic follow-up as a means to detect, prevent, and solve medication-related problems (MRPs) in inpatients, and to establish consensus strategies to solve avoidable MRPs. MATERIAL AND METHODS: An observational prospective study of 22 patients hospitalized in a Surgery Department, Hospital Infanta Margarita, Cabra (Córdoba) was conducted. Dader methodology was adapted for drug therapy follow-up in the hospital setting. RESULTS: In all, 108 MRPs were detected; 22.04% were associated with medication needs (MRP1:13.6% and MRP2: 8.5%), 40.68% with ineffectiveness (MRP3: 22.0% and MRP4: 18.6%), and 37.28% with lack of safety (MRP5: 10.2% and MRP6: 27.1%). Out of 108 MRPs found, 64 (59.3%) were avoidable; 97 pharmaceutical interventions were carried out (89.8% of cases), acting in 63 (58%) MRPs detected in cooperation with physicians, while 46 MRPs were solved (42%). We found 1 MRP in each 2.6 patients -- admission days, and 1 MRP per 4.5 patients -- admission days occurred after pharmaceutical intervention during the study period. CONCLUSIONS: The use of pharmacotherapeutic follow-up in patients admitted to this department has improved the quality of health care.

Protein sorting in yeast: the localization determinant of yeast vacuolar carboxypeptidase Y resides in the propeptide.

We have isolated cis-acting mutations in the gene encoding the yeast vacuolar protein carboxypeptidase Y (CPY) that result in missorting and aberrant secretion of up to 95% of newly synthesized CPY. The CPY polypeptides synthesized by these mutants use the late secretory pathway to exit the cell, since the late-acting sec1 mutation prevents their secretion. The mutant versions of CPY are secreted as the proCPY zymogen and are enzymatically activatable in vivo and in vitro. All the mutations, including small deletions and an amino acid substitution, map to the amino-terminal propeptide region and define a discrete yeast vacuolar localization domain whose integrity is required for efficient sorting of the CPY zymogen. Thus, the N-terminal propeptide of CPY carries out at least three functions: it mediates translocation across the endoplasmic reticulum, renders the enzyme inactive during transit, and targets the molecule to the vacuole.

Overproduction-induced mislocalization of a yeast vacuolar protein allows isolation of its structural gene.

Using an immunological screening procedure that allows the detection of yeast cells aberrantly secreting vacuolar proteins, we have isolated a cloned DNA fragment containing the structural gene for the vacuolar enzyme proteinase A (PrA; EC 3.4.23.6). A large portion of PrA is misdirected to the cell surface in cells harboring the PrA structural gene on a multicopy plasmid. This mislocalized PrA traverses the late stages of the secretory pathway and differs slightly in apparent molecular weight from the vacuolar form. A deletion in the genomic copy of the PrA structural gene eliminates immunoreactive PrA as well as the enzymatic activities of at least three other vacuolar hydrolases. In the case of the vacuolar enzyme carboxypeptidase Y (EC 3.4.16.1), the lack of activity is due to the absence of proteolytic activation of the zymogen. Thus, PrA may be required for in vivo processing of a number of yeast vacuolar hydrolases.