Prothrombin complex concentrate for emergent reversal of warfarin: an international survey of hospital protocols.

For emergent warfarin reversal, four-factor prothrombin complex concentrates (4FPCCs) are recommended by many international guidelines. We surveyed international clinical sites including members of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative. Most sites have emergent warfarin reversal protocols (53% use PCC, 25% use PCC+ plasma and 2% use plasma alone); however, variation between adjusted dosing and fixed dosing was observed.

Is blood donation an opportunity for hypertension awareness?

OBJECTIVES: To assess the blood pressure (BP) of donors, the rate of hypertensive range readings amongst donors not previously identified as hypertensive and determine the value of an informational sheet about hypertension given at the time of donation. AIM: To determine the value of screening for high BP during blood donation as a public health activity. BACKGROUND: Blood donation centres measure donor BPs before accepting donations and thus provide a unique opportunity for hypertension screening and education. MATERIALS/METHODS: An anonymous survey was completed by blood donors over 2 weeks. The survey contained 22 questions regarding demographics, BP knowledge and monitoring. Participants then received a hypertension information sheet and assessed its utility with three additional questions. RESULTS: Out of 839 survey responses received, 688 respondents reported their BP in the following categories, normotensive range: 46·9%, pre-hypertensive range: 41·7% and hypertensive range: 11·3%. Notably, of donors with hypertensive range readings, 45% reported no known history of hypertension. After reading the hypertension pamphlet, 63·9% of donors found it valuable, while 38·9% did not. Furthermore, 67% of donors said they were likely to use the information they learned, while 23% of donors said they were unlikely to do so. CONCLUSIONS: An opportunity exists for increasing hypertension awareness during blood donation. Additionally, our findings indicate that an educational pamphlet at the time of donation is valuable to donors. Overall, these findings suggest that increasing hypertension awareness as part of a blood donation screening is not only needed but also useful as a public health measure.

Counting platelets at transfusion threshold levels: impact on the decision to transfuse. A BEST Collaborative - UK NEQAS(H) International Exercise.

BACKGROUND AND OBJECTIVES: Obtaining accurate and precise platelet enumeration in automatic platelet analysers at low platelet counts is a challenge. To explore the performance of current haematology analysers in counting platelet concentrations usually used as platelet transfusion threshold. MATERIAL AND METHODS: An international exercise where four blood samples with platelet levels near usual platelet transfusion thresholds was prepared and distributed. RESULTS: The samples shipped had a platelet count of 6·3, 13·3, 21·6 and 53·0 × 10(9) /l according to the international reference method. We received 82 sets of results from nine countries. Instruments from six different manufacturers were represented. Although the mean count for each of the four samples was very similar to the values, according to the reference method (9·0, 16·2, 23·0 and 57·6 × 10(9) /l), significant variability in the results was found. Assuming that these were patient samples and the result of the count used to indicate a prophylactic platelet transfusion, undertransfusion would have occurred for 24·5% of the LP1 samples at a transfusion threshold of 10 × 10(9) /l and, at a threshold of 20 × 10(9) /l, undertransfusion would have occurred for 7·2% of the LP1 and 16·2% of the LP2 samples and overtransfusion would have occurred with 23·1% of the LP3 samples. CONCLUSION: The results suggest that significant inaccuracy exists in counting low levels of platelets and that this inaccuracy might have a significant impact in under- and overtransfusion of platelet concentrates to patients.

Role of MEK/ERK pathway in the MAD2-mediated cisplatin sensitivity in testicular germ cell tumour cells.

Testicular germ cell tumour (TGCT) is the most common malignancy in young males. Although most TGCTs are sensitive to cisplatin-based chemotherapy, significant numbers of TGCT patients still relapse and die each year because of the development of resistance to cisplatin. Previously, we first reported that a key regulator of the mitotic checkpoint, mitotic arrest deficient-2 (MAD2), was a mediator of cisplatin sensitivity in human cancer cells. In this study, we investigated whether MAD2 played a role in cellular sensitivity to cisplatin in TGCT cells and the underlying molecular mechanisms responsible. Using 10 TGCT cell lines, we found that increased MAD2 expression was correlated with cellular sensitivity to cisplatin, which was associated with activation of the MEK pathway. Treatment of cells expressing high levels of MAD2 with an MEK inhibitor, U0126, led to cellular protection against cisplatin-induced apoptosis. Inactivation of MAD2 by transfecting a dominant-negative construct in TGCT cells with high levels of MAD2 resulted in the suppression of MEK pathway and resistance to cisplatin-induced cell death. These results support previous suggestion on the involvement of mitotic checkpoint in DNA damage response in human cancer cells and demonstrate a possible molecular mechanism responsible for the MAD2-mediated sensitivity to cisplatin in TGCT cells. Our results also suggest that downregulation of MAD2 may be an indicator for identification of TGCT cancer cells that are potentially resistant to cisplatin-based therapy.

Imaging for primary hyperparathyroidism--what beginners should know.

For patients with primary hyperparathyroidism surgical removal of the hyperfunctioning parathyroid gland is curative. With advances in minimally invasive surgery, accurate pre-operative localization of the hyperfunctioning parathyroid tissue is essential to aid successful surgical treatment. The onus of identifying this hyperfunctioning parathyroid tissue therefore falls on imaging techniques such as high-resolution ultrasound, radionuclide imaging, computed tomography and magnetic resonance imaging. This article is not an exhaustive review, and its main aim is to familiarize the general radiologist, trainee radiologists and clinicians with the basics of various imaging techniques and their roles in practical management of patients with primary hyperparathyroidism.

Case report: exacerbation of hemolytic anemia requiring multiple incompatible RBC transfusions.

RBC transfusions in a patient with a history of autoimmune hemolytic anemia (AIHA) can represent both a laboratory and a clinical challenge. The development of high-titer low-avidity antibodies and antibodies to high-frequency antigens may further impair the ability to identify compatible donor RBCs. Not infrequently, incompatible RBCs must be used and the desire to increase oxygen carrying capacity conflicts with the desire to avoid exacerbating the autoimmune hemolytic process with RBC transfusions. A 66-year-old Caucasian female with coronary artery disease and a history of refractory AIHA had recently developed anemia and required multiple RBC transfusions. The patient had maintained adequate RBC counts with erythropoietin and prednisone therapy for the previous 16 months. With the recent worsening of her hemolytic anemia, she had developed angina that was treated with RBC transfusions in an outpatient setting. However, her angina increased as her RBC counts decreased, leading to hospital admission for further management of her hemolytic anemia and angina. She subsequently required multiple incompatible RBC transfusions despite increased prednisone therapy and did not improve until after coronary artery stent placement and high dose IVIG therapy. This case demonstrates the usefulness of early patient phenotyping in a case of accelerating hemolytic anemia to aid in donor RBC selection, the value of communicating with clinicians and the patient regarding the use of least-incompatible RBCs, and the importance of optimizing the patient's clinical condition to avoid ischemia. In addition, it demonstrates the value of repeated attempts with IVIG treatment despite previous refractoriness to this treatment.

Prophylactic oophorectomy in Ontario.

OBJECTIVE: To determine the indications, patterns of practice, and complication rates for prophylactic oophorectomy in Ontario. METHODS: From hospital discharge abstracts, 82 hospitals were identified where at least one patient had a prophylactic oophorectomy since 1992. Ethics approval for the chart review was obtained from 41 hospitals (50%), was denied at 10 (12%) and is pending at 31 facilities. Using the International Classification of Disease diagnostic code for family history of ovarian cancer (V16.4) and prophylactic oophorectomy (V50.42), the medical records departments were asked to retrieve the charts. One abstractor reviewed the charts using a standard form to collect demographic information, indications for surgery, details of surgery and complications. RESULTS: From 1992-1998, 263 women underwent PO in 41 hospitals. A BRCA1 or BRCA2 mutation was recorded in 16 cases. Thirty-six patients had a past history of breast cancer. In 127 women, a family history was the sole reason for surgery; the remaining 136 women had a coexisting gynecologic complaint. Laparotomy was used exclusively in 155 cases, laparoscopy in 79 and vaginal access in 12 cases. Seventeen women required conversion to laparotomy during the operation. The mean length of hospital stay was 3.7 days (0-14 days). Thirty-six women (14%) had complications. CONCLUSION: We have described the indications for surgery, trends in surgical practice and surgical complications for women receiving prophylactic oophorectomy in Ontario. Prior to prophylactic oophorectomy, the indications and benefits should be clear to both patient and physician. Optimally, all women should receive genetic counseling to help define risk for ovarian and breast cancer, medical and surgical options, impact of oophorectomy on cancer risk, risk of surgical complications, and the consequences and management of surgical menopause.

Detection of recurrent chromosomal gains and losses in primary nasopharyngeal carcinoma by comparative genomic hybridisation.

Nasopharyngeal carcinoma (NPC) is a common cancer in Southern China but rare in Western countries. To search for genetic alterations in NPC, we examined a series of 20 primary tumours with comparative genomic hybridisation. The identified common chromosomal alterations included gain of chromosomes 1q, 8, 12, 19 and 20 as well as loss of chromosomes 1p, 3p, 9p, 9q, 11q, 13q, 14q and 16q. In concordance with our previous loss of heterozygosity studies in primary NPC, a high incidence of loss was detected on chromosomes 3p (75%), 11q (70%) and 14q (65%). Losses of 9q (60%), 13q (50%) and 16q (40%) were also identified. Novel chromosomal gains were observed on chromosome 12, with a high frequency (70%). Current analysis has revealed a comprehensive profile of the chromosomal regions showing losses and gains in primary NPC. Our findings may provide an entry point for conducting further investigations to locate the putative tumour-suppresser genes and oncogenes that may be involved in the tumourigenesis of NPC.

Kes1p shares homology with human oxysterol binding protein and participates in a novel regulatory pathway for yeast Golgi-derived transport vesicle biogenesis.

The yeast phosphatidylinositol transfer protein (Sec14p) is required for biogenesis of Golgi-derived transport vesicles and cell viability, and this essential Sec14p requirement is abrogated by inactivation of the CDP-choline pathway for phosphatidylcholine biosynthesis. These findings indicate that Sec14p functions to alleviate a CDP-choline pathway-mediated toxicity to yeast Golgi secretory function. We now report that this toxicity is manifested through the action of yeast Kes1p, a polypeptide that shares homology with the ligand-binding domain of human oxysterol binding protein (OSBP). Identification of Kes1p as a negative effector for Golgi function provides the first direct insight into the biological role of any member of the OSBP family, and describes a novel pathway for the regulation of Golgi-derived transport vesicle biogenesis.

Mechanistic insights relevant to protein secretion in yeast.

During the past year, a powerful combination of genetic and biochemical approaches has yielded fascinating information with respect to the question of how proteins cross membranes and subsequently traffic between intracellular compartments of the yeast secretory pathway. Fundamental advances have been made in two specific areas. These include experiments that have provided new perspectives with respect to the nature of the soluble machinery involved in facilitating protein traffic from the cytoplasm to the lumen of the endoplasmic reticulum, and work that has provided a biochemical description of what may in effect represent a membranous ligand-gated channel that is required for protein translocation into the endoplasmic reticulum lumen.