Improving blood transfusion practice: role of a computerized hospital information system

The recent focus on medical risk and financial cost has prompted a need for better guidelines for prescribing the transfusion of blood components. In 1987, to respond to the issues of quality transfusion practice and accurate evaluation, LDS Hospital (Salt Lake City, UT) began using a computerized, knowledge-based blood-ordering system. Each transfusion request was reviewed and flagged by the computer when it did not meet the criteria established by the medical staff. The study reviewed the use of red cells, platelets, and fresh-frozen plasma in 13,082 transfusion orders for 5847 consecutive patients from July 1, 1988, through June 30, 1989. The evaluation assessed, first, the adherence of physicians to computerized criteria and, second, their adherence to the quality of transfusion practice. A high percentage of the blood units ordered met the established criteria: 91.2 percent for the red cell transfusions, 72.9 percent for platelets, and 81.7 percent for fresh-frozen plasma. From the July 1, 1987, implementation date through June 1989, the mean hematocrit of persons being transfused dropped from 28.6 to 27.7 percent (0.29 = 0.28) (p less than 0.005) and the number of orders requiring review by the quality assurance department dropped from 100 to 14 percent; moreover, there was a true-exception rate of only 0.37 percent. The use of the computer system effected the implementation of the following measures: 1) identification of the indications and establishment of clear clinical and biologic parameters for every transfusion, and 2) measurement and improvement of institutional transfusion practice. These results demonstrated the efficacy of a computerized hospital information system in implementing continuous quality improvement for transfusion practice.(ABSTRACT TRUNCATED AT 250 WORDS)     

Expression of NK-lineage markers on peripheral blood lymphocytes with T- helper (Leu3+/T4+) phenotype in B cell chronic lymphocytic leukemia

Heterogeneity within lymphocyte subsets expressing T-helper (T4+/Leu3+) or T-suppressor (T8+/Leu2+) markers was analyzed in 38 patients with B cell chronic lymphocytic leukemia (B-CLL) and in 11 age-matched controls. Co-expression of NK-lineage markers (M1, Leu7) on Leu2+ or Leu3+ cells was investigated by two-color immunofluorescence, and the proportion of granular lymphocytes within each subset was determined by cytochemical staining for acid phosphatase. B-CLL patients and normal controls had similar absolute numbers of cells per microL with T- suppressor phenotype. However, the proportion of Leu2+ cells co- expressing the Leu7 antigen was higher in the B-CLL patients than in the control subjects (54 +/- 3% v 27 +/- 4%, P less than .0001). The absolute number per microL of cells with T-helper phenotype was somewhat decreased in B-CLL patients compared with normal subjects (649 +/- 104 v 799 +/- 33, P less than .02), with a consequent decrease of the helper/suppressor ratio. Furthermore, co-expression of the Leu7 and, more strikingly, of the M1 markers was increased significantly on Leu3+ cells from B-CLL patients compared with normal controls (11 +/- 2% v 2 +/- 0.7%, P less than .002 for Leu7 and 40 +/- 5% v 4 +/- 1%, P less than .00001 for M1). Cytochemical studies showed that a large proportion of Leu3+ cells from B-CLL patients were granular lymphocytes, as suggested by the co-expression of natural killer (NK) cell markers. The emergence of a population of Leu3+ granular lymphocytes with NK markers, which is barely detectable in normal subjects, may provide an explanation for the impairment of T cell functions repeatedly described in B-CLL.     

<Emphasis Type="Italic">TP53</Emphasis> p.R337H prevalence in a series of Brazilian hereditary breast cancer families

Background

Approximately 5-10% of breast cancers are hereditary. Among hereditary syndromes, Hereditary Breast and Ovarian Cancer Syndrome (HBOC) and Li-Fraumeni Syndrome (LFS) have received the most attention. HBOC is due to mutations in the BRCA1 and BRCA2 genes and is characterized by breast adenocarcinoma and/or epithelial ovarian carcinoma. LFS is associated with germline mutations in TP53; the most frequent cancer types associated with this syndrome are sarcoma, breast cancer, leukemia, brain tumors and adrenocortical carcinomas. Other cancers related to LFS are found at lower frequencies. In Brazil, especially in the southern part of the country, a specific mutation in the TP53 gene, TP53 p.R337H, occurs at a high frequency in childhood adrenocortical tumors. It has been proposed that this mutation increases breast cancer risk in southern Brazilian women.

Methods

We carried out a case-control study to determine the prevalence of the TP53 p.R337H mutation in 28 female cancer patients attended at the Cancer Genetic Counseling Service of the General Hospital of the University of São Paulo Medical School of Ribeirão Preto who fulfilled Hereditary Breast and Ovary Cancer Syndrome genetic test criteria compared to healthy woman (controls). TP53 p.R337H mutation status was determined using the High Resolution Melting (HRM) method, followed by DNA sequencing. Fisher’s test was used to compare the prevalence of TP53 p.R337H in the patient and control groups.

Results

Two of the breast cancer cases (7.1%) and none of the controls carried the TP53 p.R337H mutation. At the time of the investigation, both cases fulfilled testing criteria for Hereditary Breast and Ovary Cancer Syndrome but not Li-Fraumeni or Li-Fraumeni-like Syndrome, based on genetic testing criteria of NCCN Clinical Practice Guidelines in Oncology (v.1.2010).

Conclusions

We suggest that genetic screening of Brazilian breast cancer patients who fulfill Hereditary Breast and Ovary Cancer Syndrome criteria and have a family history that includes other tumors of the LFS/LFL spectrum be tested for the TP53 p.R337H mutation.

     

Mechanical properties and thermal behaviour of PEGDMA hydrogels for potential bone regeneration application

Poly(ethylene glycol) hydrogels are currently under investigation as possible scaffold materials for bone regeneration. The main purpose of this research was to analyse the mechanical properties and thermal behaviour of novel photopolymerised poly(ethylene glycol) dimethacrylate (PEGDMA) based hydrogels. The effect of varying macromolecular monomer concentration, molecular weight and water content on the properties of the resultant hydrogel was apparent. For example, rheological findings showed that storage modulus (G′) of the hydrogels could be tailored to a range between approximately 14,000 and 70,000 Pa by manipulating both of the aforementioned criteria. Equally striking variations in mechanical performance were observed using uniaxial tensile testing where reduction in PEGDMA content in the hydrogels resulted in decrease in both tensile strength and Young’s modulus values. Conversely, increases in the elongation at break values were observed as would be expected. Differential scanning calorimetry and dynamic mechanical thermal analysis showed that there was an increase in Tg with an increase in the molecular weight of PEGDMA. The relationship between the initial feed ratio, molecular weight of the macromolecular monomer and the subsequent mechanical properties of the hydrogels are further elucidated throughout this study.