Deficiency of P-selectin in a patient with grey platelet syndrome

Abstract: Patient B.G. is a 29-yr-old female with a lifelong bleeding disorder characterized clinically by a highly increased bleeding time, menorrhagias, long-lasting bleeding after cuts and tooth extractions and large post-traumatic haematomas. Her coagulation tests were within normal range, platelet count was 140,000–160,000 per μl, but platelet function was impaired as demonstrated by the absence of collagen-induced aggregation, although no abnormalities were detected in aggregation response to ADP and ristocetin. Morphologically her platelets were characterized by gigantic size – average profile area was about 2.5 times higher than that of control donors, and severe deficiency of α-granules – only 16% of their number in control donors. These features taken together indicated the diagnosis of grey platelet syndrome. As has been shown by quantitative immunoblotting, patient's platelets contained small amounts of α-granule membrane protein P-selectin – about 15% of that in control donors. The content of plasma membrane glycoproteins IIb–IIIa and Ib was not reduced, suggesting the specific deficiency of α-granule membrane protein. Thus, B.G. is the second patient described in the literature (see also Lages et al, J Clin Invest 1991: 87: 919–929) with combined deficiency of α-granules and P-selectin.     

Surgical Myocardial Revascularization versus Percutaneous Coronary Intervention with Drug-Eluting Stents in Octogenarian Patients

Objective: Our goal was to compare the clinical outcomes of octogenarian (or older) patients who are referred for either surgical or percutaneous coronary revascularization.Methods: We retrospectively evaluated the outcomes of all patients 80 years of age who had undergone coronary artery bypass grafting (CABG) with an internal mammary artery or had undergone a percutaneous coronary intervention (PCI) with a sirolimus-eluting stent to the left anterior descending artery in our center between May 2002 and December 2006.Results: Of the 301 patients, 120 underwent a PCI, and 181 underwent CABG. Surgical patients had higher rates of left main disease, triple-vessel disease, peripheral vascular disease, emergent procedures, and previous myocardial infarctions (39.7% versus 3.3% [P = .001], 76.1% versus 28.3% [P = .0001], 19.6% versus 7.5% [P = .004], 15.8% versus 2.5% [P = .0001], and 35.9% versus 25% [P = .04], respectively). CABG patients had a higher early mortality rate (9.9% versus 2.5%, P = .01). There were no differences in 1- and 4-year actuarial survival rates, with rates of 90% and 68%, respectively, for the PCI group and 85% and 71% for the CABG group (P = .85). The rates of actuarial freedom from major adverse cardiac events (MACEs) at 1 and 4 years were 83% and 75%, respectively, for the PCI group, and 86% and 78% for the CABG group (P = .33). The respective rates of freedom from reintervention were 87% and 83% for the PCI group, versus 99% and 97% for the CABG group (P < .001). The 4-year rate of freedom from recurring angina was 58% for the PCI group, versus 88% for CABG patients (P < .001). Revascularization strategy was not a predictor of adverse outcome in a multivariable analysis.Conclusion: Octogenarian CABG patients were sicker and experienced a higher rate of early mortality. The 2 strategies had similar rates of late mortality and MACEs, with fewer reinterventions and recurring angina occurring following surgery.     

A Mouse Mammary Gland Involution mRNA Signature Identifies Biological Pathways Potentially Associated with Breast Cancer Metastasis

Mouse mammary gland involution resembles a wound healing response with suppressed inflammation. Wound healing and inflammation are also associated with tumour development, and a ‘wound-healing’ gene expression signature can predict metastasis formation and survival. Recent studies have shown that an involuting mammary gland stroma can promote metastasis. It could therefore be hypothesised that gene expression signatures from an involuting mouse mammary gland may provide new insights into the physiological pathways that promote breast cancer progression. Indeed, using the HOPACH clustering method, the human orthologues of genes that were differentially regulated at day 3 of mammary gland involution and showed prolonged expression throughout the first 4 days of involution distinguished breast cancers in the NKI 295 breast cancer dataset with low and high metastatic activity. Most strikingly, genes associated with copper ion homeostasis and with HIF-1 promoter binding sites were the most over-represented, linking this signature to hypoxia. Further, six out of the ten mRNAs with strongest up-regulation in cancers with poor survival code for secreted factors, identifying potential candidates that may be involved in stromal/matrix-enhanced metastasis formation/breast cancer development. This method therefore identified biological processes that occur during mammary gland involution, which may be critical in promoting breast cancer metastasis that could form a basis for future investigation, and supports a role for copper in breast cancer development. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. An erratum to this article can be found at     

Effect of age on outcome of bilateral skeletonized internal thoracic artery grafting

BACKGROUND: Elderly patients are considered to be at higher risk for coronary artery bypass grafting. Surgical techniques of arterial myocardial revascularization without vein grafts were primarily reserved for the young. This report evaluates the impact of age on the outcome of 634 consecutive patients who underwent double skeletonized internal thoracic artery grafting between April 1996 and December 1997. METHODS: Patients were stratified into five age groups: One hundred ninety-six were less than 60 years of age, 98 between 60 and 65 years, 132 between 65 and 70 years, 116 between 70 and 75 years, and 92 were older than 75 years. The groups did not differ with regard to preoperative risk factors. RESULTS: Hospital mortality was 2.5% (n = 16). Mortality of urgent and elective operations was 1.6%, and that of emergency operations was 9.7% (p < 0.001). There were 7 (1.1%) myocardial infarctions, 9 strokes (1.4%), and 10 deep sternal wound infections (1.6%). Using the Mantel-Haenszel test, there was no relation between age and hospital mortality, myocardial infarctions, strokes, or sternal infections. A correlation was found between advanced age and early unfavorable events (6.7%, 7.2%, 12.9%, 15.5%, and 15.2% in corresponding age groups, p < 0.003), and late mortality (0.6%, 1%, 1.5%, 4.3%, and 9.8%, respectively, p < 0.01). However, early return of angina was lower (2.6%, 1%, 0.8%, 0.9%, and 0%, p < 0.06). CONCLUSIONS: This retrospective, nonrandomized study suggests that older age is not a risk factor for operative mortality in patients undergoing coronary artery bypass grafting with double skeletonized internal thoracic arteries. Apart from avoiding morbidity associated with leg incisions, older patients showed an interesting trend toward lower rates of angina return. Older patients, however, sustained increased perioperative morbidity and late mortality rates.     

Pylephlebitis due to perforated appendicitis in a teenager

Pylephlebitis, a septic thrombophlebitis of the portal vein, is a life-threatening complication of intraabdominal infections, commonly associated with acute appendicitis in children, and diverticulitis in adults. A 13-year-old boy was admitted for high fever and jaundice. On the fifth day of hospitalization, ultrasound Doppler flow and Computer Tomography scan studies showed thrombosis of the portal vein and acute appendicitis. The patient was treated with antibiotics, anticoagulation and laparotomy with appendectomy. No thrombophilic risk factors were diagnosed. Our aim is to improve physicians’ awareness of this complication and emphasize the importance of early diagnosis and appropriate therapy in children in order to reduce serious complications and long-term sequels.