Antiangiogenic activity of 2-formyl-8-hydroxy-quinolinium chloride.

Tumour growth is closely related to the development of new blood vessels to supply oxygen and nutrients to cancer cells. Without the neovascular formation, tumour volumes cannot increase and undergo metastasis. Antiangiogenesis is one of the most promising approaches for antitumour therapy. The exploration of new antiangiogenic agents would be helpful in antitumour therapy. Quinoline is an aromatic nitrogen compound characterized by a double-ring structure which exhibits a benzene ring fused to pyridine at two adjacent carbon atoms. The high stability of quinoline makes it preferable in a variety of therapeutic and pharmaceutical applications, including antitumour treatment. This work is to examine the potential antiangiogenic activity of the synthetic compound 2-Formyl-8-hydroxy-quinolinium chloride. We found that 2-Formyl-8-hydroxy-quinolinium chloride could inhibit the growth of human umbilical vein endothelial cells in vitro. Using the diethylnitrosamine-induced hepatocarcinogenesis model, 2-Formyl-8-hydroxy-quinolinium chloride showed strong antiangiogenic activity. Furthermore, 2-Formyl-8-hydroxy-quinolinium chloride could inhibit the growth of large Hep3B xenografted tumour from the nude mice. We assume that 2-Formyl-8-hydroxy-quinolinium chloride could be a potential antiangiogenic and antitumour agent and it is worthwhile to further study its underlying working mechanism.

Perceptions of urgency: defining the gap between what physicians and nurses perceive to be an urgent issue.

INTRODUCTION: Through our research into the design and evaluation of technology systems to improve the quality and safety of clinical communication, we have discovered that physicians and nurses differ in perspective regarding clinical prioritization and desirable response times. This has a number of important consequences including unnecessary interruptions, escalating conflict and deterioration in interprofessional relationships. Understanding the differing perspectives on clinical prioritization, or the gap in perceived urgency, may improve interprofessional relationships. METHODS: We conducted a mixed-methods study utilizing both qualitative (semi-structured interviews) and quantitative (surveys) methods to determine the gap between perceived urgency among physicians and nurses. The survey comprised of real messages extracted from the clinical communication system that was implemented. Physicians and nurses reviewed the messages and assigned an urgency level to each. The semi-structured interviews used open-ended questions to act as a guide to highlight key themes of interest. Thematic analysis, frequency tabulation, and triangulation were used to analyze the data. RESULTS: Although the surveys demonstrated concordance between physicians and nurses when independently ranking the urgency of clinical messages (kappa=0.66 SE 0.15), agreement was only fair in comparison to the urgency identified by the original nurse who sent the message (kappa=0.22 SE 0.18). We hypothesize that clinical context has a major role in defining urgency and may explain this finding. The survey data was triangulated with the semi-structured interview data and it was determined that the desired response time significantly impacted the sender's message prioritization. For example, shift changes and anxious family members were associated with discordant prioritizations. DISCUSSION: This study demonstrated that the perceived communication urgency gap between sending nurses and receiving physicians was primarily related to timeframe and context, not clinical condition. Most disagreement occurred when nurses used urgent messaging for time sensitive but not clinically urgent issues in an effort to expedite the resolution of their issue by the physicians. These results indicate the need for clinical communication systems to incorporate decision support around both clinical prioritization and expected response time in their design. Effective interprofessional communication is essential to the provision of safe, quality-based healthcare; these results highlight some of the sociotechnical aspects of health information technology implementation that must be considered.

5-(Dimethylamino)-N-(4-ethynylphenyl)-1-naphthalenesulfonamide as a novel bifunctional antitumor agent and two-photon induced bio-imaging probe.

A novel compound, (5-(dimethylamino)-N-(4-ethynylphenyl)-1-naphthalenesulfonamide), was prepared and characterized; it shows dual functional roles as an effective antitumor and a two-photon induced bio-imaging agent.

Antiproliferative activity of the extract of Gleditsia sinensis fruit on human solid tumour cell lines.

BACKGROUND: The fruit extract of Gleditsia sinensis Lam. (GSE) is a traditional herbal medicine that is saponin-rich. However, its activity on solid tumour cell lines has never been demonstrated. METHODS: The activity of GSE was demonstrated in four cancer cell lines (breast cancer MCF-7, MDA-MB231, hepatoblastoma HepG2 and oesophageal squamous carcinoma cell line SLMT-1) using MTT assay, anchorage-independent clonogenicity assay, DNA laddering and in situ cell death detection. RESULTS: The mean MTT(50) (the mean concentration of GSE to reduce MTT activity by 50%) ranged from 16 to 20 microg/ml of GSE. An anchorage-independent clonogenicity assay showed that all of the four solid tumour cell lines gradually lost their regeneration potential after treatment with GSE, DNA fragmentation and TUNEL analysis demonstrated that the action of GSE is both dose- and time course-dependent. CONCLUSIONS: Our results suggest that GSE has a cytotoxic activity and can induce apoptosis in human solid tumour cell lines.

Vitamin B12 deficiency--need for a new guideline.

OBJECTIVES: Many patients with vitamin B12 deficiency do not have anemia or macrocytosis, but the prevalence of B12 deficiency in patients without macrocytosis is not known. METHODS: We investigated the prevalence of B12 deficiency among patients with normocytosis and microcytosis and recommended a screening strategy. All patients (n = 3714) with serum B12 measured at the Prince of Wales Hospital in 1996 were reviewed. The prevalence of serum B12 less than 140 pmol/L was determined for the following patient subgroups: younger than 70 y, older than 70 y, anemic, non-anemic, macrocytic, normocytic, microcytic, documented iron deficiency, and documented thalassemia. RESULTS: The prevalence of B12 deficiency (<140 pmol/L) ranged from 4.8% to 9.8% among the different subgroups. CONCLUSIONS: Whatever screening criteria were used, a significant number of B12-deficient patients will be missed. Therefore, there may be a case for universal vitamin B12 screening.

To err is human nature. Can transfusion errors due to human factors ever be eliminated?

BACKGROUND: Fatal hemolytic transfusion reaction due to ABO incompatibility occurs mainly as a result of clerical errors. Blood sample drawn from the wrong patient and labeled as another patient's specimen will not be detected by the blood bank unless there is a previous ABO grouping result. METHODS: In Hong Kong, we had designed a transfusion wristband system--portable barcode scanner system to detect such clerical errors. The system was well accepted by the house staff and had prevented two BO mismatched transfusion. Other current system of patient's identification may have similar results, but the wristband system has the advantages of being simple, inexpensive and easy to implement. The Hong Kong Government is planning to replace the personal identity card for all citizens with an electronic smart card by 2003. If the new card contains the person's detailed red cell phenotypes in digital code, then the phenotypes of all blood donors and admitted patients will be readily available. It is feasible to issue phenotype-matched blood to patients without any need of pre-transfusion testing, therefore eliminating mismatched transfusions for most patients. RESULTS: Our pilot study of 474 patients showed that the system was safe and up to 98% of admitted patients could be transfused without delays. CONCLUSIONS: Patients with rare phenotypes, visitors or illegal immigrants may still need pre-transfusion antibody screen, but if most patients can be issued blood units without testings, the potential savings in health care amount to US$14 million/year.

Provision of phenotype-matched blood units: no need for pre-transfusion antibody screening.

BACKGROUND AND OBJECTIVES: The Hong Kong government is planning to introduce an electronic smart identity card for all seven million citizens in 2003. If the smart card contains the full red cell phenotype/genotype of the individual, it may be possible to transfuse phenotype-matched blood units without pre-transfusion antibody screening. We conducted a feasibility study. DESIGN AND METHODS: Red cell phenotype was determined for 407 donor blood units and 493 patients for whom an antibody screen had been ordered. The computer program selected phenotype-matched blood from the donor stock for the patients according to actual transfusion request. For patients with a positive antibody screen, full crossmatching was carried out with the computer-selected phenotype units. The frequencies of the various red cell phenotypes in the population were calculated from Red Cross data of antigen frequencies. The probabilities of finding at least one unit of phenotype-matched blood from a 300-unit hospital stock and a 4,000-unit Red Cross stock were determined for each phenotype. Cost analysis was performed. RESULTS: Ninety-two out of 493 patients received a total of 395 blood units. The required number of phenotype-matched blood units could be found for 92 patients using a 300-unit pool and for all patients using a 4,000-unit pool. We calculated that phenotype-matched blood could be provided for more than 98% of patients without antibody screening. The total cost of the project is US$ 98 million with potential savings of US$ 14 million per year. INTERPRETATION AND CONCLUSIONS: It is feasible and cost-effective to transfuse patients with phenotype-matched blood without antibody screening using a smart card system.

Successful engraftment in two adult patients with severe aplastic anemia using nonmyeloablative conditioning followed by unrelated HLA-mismatched cord blood transplantation.

Umbilical cord blood as an alternative source of hematopoietic stem cells and nonmyeloablative conditioning are very exciting new developments in transplantation. We report here mixed chimerism in two adult patients with severe aplastic anaemia using nonmyeloablative conditioning and two-antigen mismatched cord blood transplantation resulting in satisfactory clinical response. Our results suggest that such transplant is possible with minimal toxicity.

Transfusion of peripheral blood stem cells from donor homozygous for a shared HLA-haplotype: avoiding fatal transfusion-associated graft-versus-host disease while preserving anti-leukemic effect.

BACKGROUND: Fatal transfusion-associated graft-versus-host disease was observed in immunocompetent patients transfused with blood from donors homozygous for a shared haplotype with the recipient (the P-F1 barrier). We tested whether it was possible to carry out successful transplantation in a patient with relapsed acute myeloid leukemia, using peripheral blood stem cells from his HLA-homozygous brother (HLA A2, B46, DRB1 901) who shared a haplotype with the patient (HLA A2, B46,75, DRB1 901,12). METHODS: A CD34 positively selected cell fraction (5.46x 10(6) CD34 cells/kg) was infused first, followed by subsequent infusion of graded doses of donor T cells (total 7.25x10(7) T cells/kg). Nonmyeloablative chemotherapy with idarubicin and cytarabine was given during the transplantation to reduce the leukemic burden and facilitate engraftment. Polymerase chain reaction with the VNTR primers, D1S80, was used to detect engraftment. RESULTS: Complete remission (>300days) and successful donor engraftment (90%) were achieved. CONCLUSIONS: Peripheral blood stem cells transplantation from a donor with a homozygous shared haplotype is possible with a minimal preparative regimen.

Improvement in transfusion safety using a specially designed transfusion wristband.

Fatal haemolytic transfusion reaction due to ABO incompatibility occurs mainly as a result of clerical error. A blood sample drawn from the wrong patient and labelled as another patient's will not be detected by the blood bank unless there is a previous ABO grouping result. We report here the detection of such clerical error by the use of a specially designed transfusion wristband. The wristband has the following special features: (i) once attached, it cannot be removed except by cutting; (ii) it has a pocket containing a transfusion label; (iii) a unique transfusion barcode is printed on each transfusion label and the corresponding wristband simultaneously by computer technology; (iv) a transfusion label removed from the wristband after attachment to the patient has a characteristic tear-mark distinguishing it from one removed prior to attachment. The blood bank only accepted those specimens bearing the tear-marked transfusion labels. All blood units for this patient were labelled with this unique transfusion code together with the patient's details. The nurses counter-checked the transfusion code on the blood units against the transfusion code on the patient's transfusion wristband prior to transfusion. If the blood sample for compatibility testing was drawn from the 'wrong' patient, the intended patient either did not carry a wristband or the transfusion codes did not match at all. Pretransfusion compatibility tests were performed on 2189 patient samples using this procedure. It was well accepted by both ward and blood bank staff. Two potential mismatched transfusions were avoided. These two clerical errors would not have been detected because neither patient had previous ABO grouping results.

Yuehchukene, a bis-indole alkaloid, and cyclophosphamide are active in breast cancer in vitro.

Yuehchukene (YCK) is a novel bis-indole alkaloid with weak estrogenic activity. Biochemical studies showed that YCK could attenuate estrogenic action. In this study, the response of MCF-7, an estrogen-receptor-positive breast cancer cell line, under different combinations of estradiol, cyclophosphamide and YCK, was tested. From the dose-response curve, we discovered that 10(-2) M cyclophosphamide, even in its so-called 'bio-inert' form, could inhibit MCF-7 cell growth. However, the cytotoxic effect of cyclophosphamide was lost by reducing its concentration to approximately 1 x 10(-3) M. On the other hand, a low concentration ( approximately 10(-8)-10(-9) M) of YCK was found to potentiate the cytotoxic effect of cyclophosphamide on the MCF-7 cell line. Such an effect was absent in the estrogen-receptor-negative cell line MDA-MB-231. These findings, together with the dual role of a mixed estrogen and anti-estrogen effect, suggested that YCK and cyclophosphamide can be a potential combination in chemo-hormonal therapy for breast cancer.

Comparison of late results of balloon valvotomy in mitral stenosis with versus without mitral regurgitation.

Balloon mitral valvotomy (BMV) is safe and effective in patients with mitral stenosis (MS) and coexisting mild mitral regurgitation (MR). Influence of preexisting MR on late outcome of BMV is under evaluation. We included 77 patients without MR and 72 with MR in this study, and compared their immediate and late results in a mean follow-up of 33 +/- 24 months after BMV. Patients with coexisting MR were older and more frequently had significant valvular calcium and atrial fibrillation than patients without MR. After BMV, mitral valve gradient decreased, and cardiac output and mitral valve area by planimetry increased significantly (all p = 0.0001) in both groups. There was no difference in values of mitral valve gradient and cardiac output after BMV between the groups. Mitral valve area was significantly smaller in patients with preexisting MR. During follow-up, there were 11 patients (14%) in the group without MR and 24 (33%) in the group with MR developed cardiac events (p = 0.006). Cumulative event-free survival was 90% at the second year, 87% at the fourth year, and 69% at the sixth year, respectively, in the group without MR versus 78%, 62%, and 37%, respectively, in the group with MR (p = 0.0014). Cox regression showed that preexisting MR was a significant predictor for late cardiac events with a threefold increased hazard risk (p = 0.0025), but age, valvular calcium, echocardiographic score, and cardiac rhythm also played a culpable role. We conclude that preexisting MR is an important risk factor for poor, late outcome of BMV.

Lack of structural rearrangement in c-kit and stem cell factor genes in Hong Kong Chinese patients with myelodysplastic syndromes or acute myeloid leukaemia.

Stem cell factor is a haemopoietic growth factor that interacts with the c-kit-encoded transmembrane tyrosine kinase receptor during signal transduction in haemopoietic progenitor stem cells. We have screened 127 Chinese patients with myelodysplastic syndromes or acute myeloid leukaemia for structural rearrangements in the stem cell factor and c-kit genes using Southern blot analysis. No structural rearrangements were detected in any of the bone marrow samples that were tested. It seems that structural rearrangements in the stem cell factor and c-kit genes are rare in Hong Kong patients who have a haematological malignancy.

A novel prognostic scoring system to predict late outcome after percutaneous balloon valvotomy in patients with severe mitral stenosis.

We developed a prognostic scoring system to predict the outcome of follow-up after balloon mitral valvotomy. The system incorporates seven variables before valvotomy: age, New York Heart Association class, fluoroscopic calcification, echocardiographic score, cardiac rhythm, mitral regurgitation, and mitral valve area. Each variable was coded with either 0 or 1 and a total score was between 0 and 7. The study included 150 patients with a mean follow-up of 33 +/- 24 months. In patients with scores of 0-1, 2-3, 4-5, and 6-7, the estimated cardiac event-free survival rate was 97%, 94%, 86%, and 68%, respectively, at 1 year; 95%, 88%, 74%, and 47%, respectively, at 3 years; and 92%, 82%, 61%, and 30%, respectively, 5 years after valvotomy (p = 0.0001). The hazard risk ratio for cardiac events was 1.7 times greater for every step up of the score (p = 0.0001). Our scoring system provides a simple but effective method to predict late outcome of balloon mitral valvotomy.

Low frequency of c-kit expression and detection of an aberrant Kit message among Hong Kong Chinese myelogenous leukaemia patients.

The c-kit proto-oncogene encodes a transmembrane tyrosine kinase receptor. It is expressed by the primitive CD34 positive haemopoietic stem cells and interacts with the Kit ligand for signal transduction. It was reported to be expressed in over 80% of acute myelogenous leukaemia (AML) patients in North America and Japan. We analyzed 20 AML patients for c-kit expression using either Northern blot analysis or flow cytometry with the YB5.B8 anti-c-kit antibodies. Only 6 out of 20 AML patients expressed the c-kit mRNA or protein product. However, a previously unreported abnormal sized 1.7-1.9 kb transcript was detected in the blast cells of 1 AML patient, 1 acute mixed lineage leukaemia patient and 1 chronic myelogenous leukaemia (CML) patient in myeloblastic transformation. Our data suggested that in most Hong Kong Chinese AML patients, leukaemia transformation may have occurred at a c-kit negative stage. Alternatively, the abnormal sized c-kit transcript that was detected in some Chinese myeloid leukaemia patients may represent an aberrant c-kit receptor that plays an important role in leukaemogenesis.

Expression of an abnormal sized c-kit transcript in Hong Kong Chinese acute lymphoblastic leukaemia patients.

Blast cells from a majority of acute myelogenous leukaemia (AML) patients express c-kit mRNA. However, c-kit expression has not been observed in patients with acute lymphoblastic leukaemia (ALL) and lymphoproliferative disease. We report here the detection of an abnormal sized c-kit mRNA in two Hong Kong Chinese patients with pre-B ALL and common ALL.