Drug-related problems on hospital admission: relationship to medication information transfer

BACKGROUND: Patients with end-stage renal disease (ESRD) are at risk for drug-related problems (DRPs), especially on hospital admission. OBJECTIVE: To identify and characterize the DRPs experienced by patients with ESRD on admission and investigate how these DRPs could be related to gaps in medication information transfer. METHODS: Patients with ESRD admitted to the hospital were prospectively identified and clinically assessed by a pharmacist to identify and categorize DRPs on admission. Each DRP was evaluated to determine whether it could have been caused by a gap in medication information transfer. For DRPs caused in this manner, the interface in the information transfer process where the gap may have occurred was determined. RESULTS: A total of 199 DRPs were identified in 47 patients with ESRD over a 12 week period. Ninety-two percent of patients had at least one DRP on admission, with an average of 4.2 +/- 2.2 DRPs per patient. The most common DRP identified was indication for drug therapy--patient requires drug but is not receiving it (51.3%). Of the total DRPs, 130 (65%) were related to gaps in medication information transfer, with 21.5% occurring between the inpatient hospital and the ambulatory clinic pharmacists and 17.7% between the admitting physician and the patient. CONCLUSIONS: Results of this study demonstrate that, in patients with ESRD, DRPs on admission are frequently related to gaps in medication information transfer between healthcare professionals and also between healthcare providers and patients. Improved communication is required at medication information transfer interfaces to prevent these DRPs.     

Ultrastructural features of the lining epithelium of the vas deferens of Agouti paca

The epididymal epithelium of Agouti paca, a wild South American rodent, was basically formed by principal and basal cells. Principal cells were closely related to processes of adsorptive endocytosis, phase-fluid endocytosis and also secretion originating from their cytoplasmic ultrastructural features. Principal cells were also characterized by the presence of vesicles of several shapes, sizes and internalized content occurring in smaller pits, pale small vesicles next to the apical brush border of microvillus, as well as coated vesicles, smooth surface vesicles and great vesicles. Multivesicular bodies, endosomes and lysosomes were mainly observed in supranuclear position. Moreover, presence of an apocrine secretory process was demonstrated by the occurrence of apical cytoplasmic expansions projecting into the vas deferens luminal compartment. Basal flattened cells without luminal surface contact occurred next to the basement membrane of the ductus, and did no exhibit special ultrastructural features.     

DAZ gene copies: evidence of Y chromosome evolution

The DAZ gene, a contributing factor in infertility, lies on the human Y chromosome's AZFc region, whose deletion is a common cause of spermatogenic failure. Y chromosome binary polymorphisms on the non-recombining Y (NRY) region, believed to be a single occurrence on an evolutionary scale, were typed in a sample of fertile and infertile men with known DAZ backgrounds. The Y single-nucleotide polymorphisms (Y-SNPs) with low mutation rates are currently well characterized and permit the construction of a unique phylogeny of haplogroups. DAZ haplotypes were defined using single-nucleotide variant (SNV)/sequence tagged-site (STS) markers to distinguish between the four copies of the gene. The variation of 10 Y chromosome short tandem repeat (STRs) was used to determine the coalescence age of DAZ haplotypes in a comparable time frame similar to that of SNP haplogroups. An association between DAZ haplotypes and Y chromosome haplogroups was found, and our data show that the DAZ gene is not under selective constraints and its evolution depends only on the mutation rate. The same variants were common to fertile and infertile men, although partial DAZ deletions occurred only in infertile men, suggesting that those should only be used as a tool for infertility diagnosis when analysed in combination with haplogroup determinations.     

Synthetic and natural polycations for gene therapy: state of the art and new perspectives

Currently, the major drawback of gene therapy is the gene transfection rate. The two main types of vectors that are used in gene therapy are based on viral or non-viral gene delivery systems. There are several non-viral systems that can be used to transfer foreign genetic material into the human body. In order to do so, the DNA to be transferred must escape the processes that affect the disposition of macromolecules. These processes include the interaction with blood components, vascular endothelial cells and uptake by the reticuloendothelial system. Furthermore, the degradation of therapeutic DNA by serum nucleases is also a potential obstacle for functional delivery to the target cell. Cationic polymers have a great potential for DNA complexation and may be useful as non-viral vectors for gene therapy applications. The objective of this review was to address the state of the art in gene therapy using synthetic and natural polycations and the latest strategies to improve the efficiency of gene transfer into the cell.     

Microleakage in conventional and bonded amalgam restorations: influence of cavity volume

This study verified the relationship between the volume and microleakage of conventional and bonded amalgam restorations. Also, the microleakage influence of intermediate materials, substrates and the direction of sectioning was investigated. Fifty-six bovine incisors were selected. Standard Class V cavities were prepared in buccal and lingual surfaces. For each tooth, two cavity sizes were prepared, corresponding to two cavity volumes: one larger (A) and the other smaller (B). The cervical wall was located in cementum/dentin and the incisal wall in enamel. The teeth were distributed in four groups (n=28) according to the intermediate material employed (glass-ionomer cement, resin cement, adhesive system and copal varnish-control). The materials were applied following manufacturers' directions. After restoration, the teeth were submitted to thermal cycling. They were then immersed in a dye solution and sectioned in two directions inciso-cervical (IC) and mesio-distal (MD) sections to evaluate the microleakage. Data were subjected to non-parametric statistical analysis (Wilcoxon's paired test and Kruskal-Wallis test). No significant difference was found between the two cavity sizes. Leakage in enamel was statistically lower than in the cementum/dentin interface (p < 0.05). In some situations, glass-ionomer or resin cement lined amalgam restorations presented less dye leakage than copal varnish lined restorations (p < 0.05). No significant difference was observed in microleakage between IC or MD sectioning. Within the limitations of this study, it was concluded that cavity size and direction of section were not significant factors for microleakage, while substrate and intermediate materials had a significant effect on the sealing ability in amalgam restorations.     

A molecular study of first and second RB1 mutational hits in retinoblastoma patients

RB1 mutations accountable for biallelic inactivation are crucial events in the development of retinoblastoma because a first mutation (M1) predisposes to retinoblastoma while a second mutation (M2) is required for tumor development. Mutational analyses of this gene showed a wide spectrum of genetic alterations (single base substitutions, insertions, or deletions, as well as small and large deletions). The most frequent second hit in retinoblastoma patients is loss of heterozygosity (LOH) followed by promoter methylation. Molecular analyses of RB1 mutations were conducted in 36 patients (20 unilateral and 16 bilateral) using polymerase chain reaction-mediated single-strand conformation polymorphism (SSCP) analysis, sequencing, and LOH analysis. Sixty-four amplified fragments showing abnormal SSCP patterns were sequenced, and mutations were confirmed in five patients (13.89%). Four mutations were located at coding regions, and a fifth one was found at an exon-intron junction. Two mutations were C-->T transitions, two were small-length deletions, and one was a G-->A transition. A total of 47.05% patients showed LOH. In one patient, the parental origin of the mutated allele was detected: the allele retained in the tumor was the paternal one. This work helps to characterize the spectrum of mutations in the Brazilian population, and to confirm that formaldehyde-fixed paraffin tissue can provide valuable information on the RB1 status in retinoblastoma patients.     

Comparison of the cytotoxic effect of lapachol, α-lapachone and pentacyclic 1,4-naphthoquinones on human leukemic cells

The pentacyclic 1,4-naphthoquinones 1a–d were cytotoxic (IC₅₀ ∼ 2–7 μM) to human leukemic cell lines K562 (oxidative stress-resistant), Lucena-1 (MDR phenotype) and Daudi. Fresh leukemic cells obtained from patients, some with the MDR phenotype, were also sensitive to these compounds. The pentacyclic 1,4-naphthoquinones 1a and 1c induced apoptotic cell death in cells from leukemic patients as determined by flow cytometry. Conversely, the cell lines were highly insensitive to lapachol (2) and α-lapachone (3). Mitomycin-C inhibited cell proliferation at concentrations as low as 0.5 μM. The low toxicity against lymphocytes activated by phytohemagglutinin shows that these compounds are selective for the cancer cells studied. Previous data suggest that these compounds (1a–d) can be bioactivated in situ by reduction followed by rearrangement leading to enones, which are powerful alkylating agents. In contrast, lapachol (2) and β-lapachone (3), which cannot be bioactivated by reduction, showed little activity against the same cell lines.     

Pityriasis lichenoides et varioliformis acuta: a disease spectrum

Pityriasis lichenoides et varioliformis acuta (PLEVA), or Mucha–Habermann disease (MHD), is a cutaneous disorder evident with crops of erythematous macules and papules, usually on the trunk and flexural areas of the extremities. Its etiology remains unknown. PLEVA is speculated to be an inflammatory reaction triggered by certain infectious agents, an inflammatory response secondary to T‐cell dyscrasia, or an immune complex‐mediated hypersensitivity. Histologic examination of a skin biopsy specimen is the standard for the identification of PLEVA, but definitive diagnosis may be difficult. Apart from the febrile ulcerative variant, which may be fatal, PLEVA tends to be self‐limited in its course. Treatment is targeted mainly at the symptomatic relief of pruritus.