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.

The effect of ACTH and cortisol on aldosterone and cortisol clearance and distribution in plasma and whole blood.

The mechanisms of increased aldosterone and cortisol metabolic clearance rates (MCR) following ACTH or cortisol administration were studied in 13 subjects undergoing cardiac catheterization and in 9 healthy controls. In control subjects, the MCR (plasma) of both steroids increased by 29% (aldosterone: from 936 +/- 57 to 1204 +/- 55 l/day/m2, cortisol: from 205 +/- 12 to 264 +/- 17 l/day/m2 +/- SE) after ACTH (12 units/h) for 1 to 4 h, and by 20 and 32%, respectively, after cortisol (12 mg/h) for 1 to 2 h. In contrast, aldosterone MCR (whole blood) did not change with ACTH or cortisol administration (from 1276 +/- 57 to 1330 +/- 59 l/day/m2), indicating that the plasma MCR increase results from a redistribution of aldosterone from plasma to red cells. Aldosterone splanchnic extraction was 92 +/- 1% (n = 12) with normal morning cortisol levels, and extraction was unchanged after ACTH administration. For cortisol, however, the splanchnic extraction increased from 8 +/- 0.8% to 17.8 +/- 5.0%, and the MCR (whole blood) likewise increased by 15 to 31% (from 295 +/- 23 to 357 +/- 30 l/day/m2), after ACTH or cortisol administration. In vivo and in vitro measurements (at 37 C) of tracer aldosterone concentration in plasma and in red cells showed an increase in distribution to red cells with increasing cortisol concentrations. The results suggest that a fraction of aldosterone is bound in plasma and displaced by cortisol into red cells. There is an increased aldosterone plasma MCR, but unaltered whole blood MCR, since the liver extracts aldosterone almost completely from both plasma and red cells. The increase in cortisol MCR (plasma) results from both an increased splanchnic extraction as plasma binding sites approach saturation and a redistribution into red cells.

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.

Percutaneous double balloon valvotomy for severe rheumatic mitral stenosis.

Percutaneous double balloon valvotomy for severe rheumatic mitral stenosis was successfully performed in 281 of 285 consecutive patients. The changes evoked were a decrease of the mean transvalvular gradient from 16 +/- 7 to 5 +/- 3 mm Hg, an increase in cardiac output from 3.8 +/- 1.0 liters/min to 5.4 +/- 1.5 liters/min and an increase in mitral valve area from 0.86 +/- 0.24 cm2 to 2.41 +/- 0.54 cm2. The mean pulmonary artery pressure decreased from 37 +/- 13 mm Hg to 27 +/- 12 mm Hg and the pulmonary vascular resistance decreased from 307 +/- 181 to 238 +/- 122 dynes/s/cm-5. Symptomatic improvement occurred in 272 of the 285 (95%) patients. There were 3 procedure-related deaths (1%). Postdilatation mitral regurgitation was not significant in most patients. Therefore, this procedure can be performed at a low risk with effective results and a fast recovery.

Clinical data versus noninvasive testing as an estimate of coronary status.

The step from coronary angiography to surgery is taken primarily on the basis of the ejection fraction (EF) and number of diseased vessels (NV), taken jointly as coronary status (CS). This study reviewed (1) how well EF, NV and CS are estimated from clinical data, (2) how much improvement is gained by adding noninvasive data, (3) how good this model is when applied to a larger cohort and (4) whether the decision to angiography can be made on the basis of CS estimated from clinical data alone. A quantitative definition of CS was established as a principal component of EF and NV. Estimates of EF, NV and CS were made from clinical data of 60 patients. Correlations with the actual values were EF 87%, NV 93% and CS 93%. When noninvasive data were added to this model, the correlations increased to EF 95%, NV 99% and CS 98%. When the clinical data model was applied to 169 patients, the correlations decreased to EF 77%, NV 71% and CS 74%. CS estimated from clinical data alone was set up as a test for angiography for 169 patients. This test had a sensitivity of 98% and a specificity of 63%, demonstrating the feasibility of using clinical data alone in deciding angiography.

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.

Thromboembolism in mitral porcine valve recipients.

A low incidence rate of thromboembolism has been reported in mitral porcine valve recipients. In contrast, 5 of 22 single mitral porcine valve recipients (23 percent) followed up in our clinic for a mean of 16 months had thromboembolic events. All patients but one were receiving long-term anticoagulant therapy. One thromboembolic event resulted in death, three in permanent neurologic deficits and one in a peripheral arterial occlusion. All five patients with emboli had atrial fibrillation and left atrial enlargement. Three had thromboembolic events before porcine heart valve implantation. In addition, five mitral porcine valve recipients who were not receiving anticoagulant therapy were examined at autopsy. Thrombus was identified in the left atrium in three patients, at the tissue-valve interface (sewing ring) in two, on the porcine valve cusps in one and in the right atrium in one. Factors influencing thrombus formation such as left atrial enlargement, atrial fibrillation and a prosthetic device are present after mitral porcine valve implantation and are indications for long-term anticoagulation therapy.

Clinical experience with the Smeloff-Cutter aortic valve prosthesis: an 8-year follow-up study.

A total of 46 patients who survived aortic valve replacement with the present model Smeloff-Cutter prosthesis between 1968 and 1973 were followed up postoperatively. All patients received oral anticoagulant therapy. The average age at implantation was 44 +/- 13 (mean +/- standard deviation) years; 36 patients were male and 10 were female. The valve damage was caused by rheumatic disease in 19 (41 percent), infective endocarditis in 14 (30 percent), congenital heart disease in 7 (15 percent) and other factors in 6 (13 percent). Late death occurred in eight patients (17 percent). All available patients were followed up until December 1976. During the 8 years of follow-up study, seven patients, including four heroin addicts, had postoperative endocarditis (15 percent); five of the seven had cerebral involvement, possibly from septic emboli. Four patients were reoperated on; three had active endocarditis and one had a high transvalve pressure gradient. The mean follow-up time was 4.9 years per patient. Of the 38 living patients, 33 have functional improvement and are still being followed up. Only one patient had a bland embolism to a systemic artery. No ball variance or other types of material failure have been detected. Although the chronic aspects of valve disease remain after prosthetic valve replacement, the Smeloff-Cutter aortic prosthesis deserves strong consideration when selecting a rigid prosthesis for aortic valve replacement.

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.

Effects of treadmill exercise on total and myocardial creatine phosphokinase.

The percentage of increase in total and MB creatine phosphokinase (CPK) after treadmill exercise was determined in 29 patients--ten patients with ST segment depression greater than 1 mm (group 1) and 19 patients with no ST segment depression (group 2). Values were determined pretest and 6, 12, and 24 hours after exercise. The mean exercise duration was 8 min, 18 sec. Total CPK increased within the normal range 12 hours after exercise in group 1 patients exercising less than 8 min, 18 sec, and in all patients exercising longer. The MB CPK remained unchanged after exercise in all patients. These data suggest that while normal range variation of total CPK occurs after treadmill exercise testing, the myocardium does not release MB CPK, regardless of the level of treadmill exercise our patients performed or the development of presumed ischemic ST segment responses. Abnormal elevation of MB CPK suggests myocardial damage.

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.

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.

Angiographic demonstration of an acquired internal mammary-to-pulmonary artery fistula.

A patient with a continuous murmur due to flow through an internal mammary-to-pulmonary artery fistula is described. Previously reported cases have been thought to be congenital in origin. A history of an anteriorly placed chest tube suggests an acquired etiology for this malformation.

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.

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.