Duration of increased bleeding tendency after cessation of aspirin therapy

BACKGROUND: Aspirin has a significant effect on hemostasis, so it is often recommended that patients taking aspirin discontinue treatment before elective surgery. While off aspirin, these patients may be at risk of thrombosis. The optimum period of time that aspirin should be withheld is controversial. The aim of this study was to establish the duration of the antihemostatic effect of prolonged aspirin therapy. STUDY DESIGN: In a prospective study, 51 healthy volunteers were randomly assigned into 3 groups, each receiving an identical tablet for 14 days. One group received a placebo tablet; individuals in the other two groups received either 75 mg or 300 mg of aspirin once a day. Template bleeding times and specific platelet function testing (using the PFA-100; Dade Behring) were carried out on subjects before therapy and again after its completion until they returned to baseline. RESULTS: Thirty-eight volunteers complied sufficiently with the protocol to provide useful results. All bleeding times normalized within 96 hours and all platelet function tests within 144 hours after stopping aspirin. There was no demonstrable hemostatic defect in any volunteer persisting by or beyond the sixth day after treatment cessation. There was no apparent difference in duration of effect between those taking either 75 mg or 300 mg of aspirin. CONCLUSIONS: This study uses sensitive measures of platelet function to demonstrate the duration of increased bleeding tendency after withdrawal of aspirin therapy. It supports discontinuation of aspirin therapy 5 days before elective surgery (with the operation being performed on the sixth day).     

Recent advances in immunotherapy of B-CLL using ex vivo modified dendritic cells

Chronic lymphocytic leukemia (CLL) results from the relentless accumulation of small mature, slowly dividing, monoclonal B-lymphocytes. The clinical course is heterogeneous, some patients with aggressive form of the disease progressing rapidly with early death while others exhibit a more stable, possibly, non-progressing indolent type of the disease lasting many years. Despite progress in modern treatment modalities, relapse invariably occurs and disease still remains incurable. The clinical management of CLL is therefore challenging and considerable effort has been directed towards novel therapeutic strategies aimed at reducing minimal residual disease which can increase remission duration. Recent insight into the role of dendritic cells (DCs) as pivotal antigen presenting cells that initiate immune responses may provide the basis for generating more specific and effective immune responses. Ex-vivo modified and monocyte-derived DCs represents a promising approach within the context of CLL. However, understanding the relationship between DCs and the cellular immune response is crucial in devising strategies for manipulating immune responses. After a brief survey of general properties of DCs, this review focuses on the different approaches exploiting monocyte-derived DCs in CLL, which may help to design novel strategies for phase-I clinical trials.     

Three dimensional reconstruction of a human breast carcinoma using routine laboratory equipment and immunohistochemistry

AIMS: To establish a three dimensional reconstruction of an invasive breast carcinoma using basic laboratory equipment to evaluate and characterise the spatial arrangement of the parenchymal cells of the breast. METHODS: One hundred and twenty eight sequential 4 microm sections (20 microm apart) of the tumour were stained immunohistochemically with an epithelial specific marker (AE1/AE3) or tumour specific marker (c-erbB-2) to reconstruct two different three dimensional images of the normal and malignant parenchymal cells. Sections were digitally imaged using a microscope, scanner, and digital camera linked to a conventional personal computer. Accurate alignment of the digitalised images was carried out using a semiautomatic graphical method of manual interaction, using the cross correlation coefficient as a goodness of fit measure, and an automatic search algorithm using the Fibonacci search algorithm for automatic alignment. The volume was reconstructed using maximum, minimum point projection and "back to front" opacity blending. RESULTS: The quality of the reconstructed images was distinct and perfect, providing a comprehensive and explicit view of the normal and malignant parenchymal tissues of the breast that is not possible by viewing two dimensional histological sections. Specifically, this approach showed the spatial arrangement of the tumour cells and their relation to the surrounding tissues at a high resolution. CONCLUSION: This simple and reproducible approach enables the spread and infiltration of invasive carcinoma to be understood and could also be used to analyse the spatial relation between atypical hyperplastic and malignant in situ lesions of the breast.     

Toxic myopathies

Muscle tissue is highly sensitive to drugs and toxins because ot its high metabolic activity and potential sites for disruption of energy-producing pathways. Early recognition of toxic myopathies is important, as they potentially are reversible on removal of the offending toxin, with greater likelihood of complete resolution the sooner this is achieved. Clinical features range from mild muscle pain and cramps to severe weakness with rhabdomyolysis, renal failure, and even death. The pathogenic bases can be multifactorial. This article reviews drugs responsible for common types of toxic myopathy and their clinical and histopathologic features and illustrates possible underlying cellular mechanisms.     

Molecular diagnosis of inheritable neuromuscular disorders. Part I: Genetic determinants of inherited disease and their laboratory detection

Understanding of the genetic basis of inheritable neuromuscular disorders has grown rapidly over the last decade, resulting in improved classification and understanding of their pathogenesis. A consequence of these advances has been the development of genetic tests of blood specimens for the diagnosis of many of these diseases. For many patients, these blood tests have eliminated the need for other more invasive diagnostic tests such as muscle or nerve biopsy, and for some patients, reduced exposure to immunosuppressive medication and its complications. The first part of this review focuses on the nature of genetic disorders, the laboratory methods used in the performance of genetic tests, and general practical aspects of their use and interpretation. The second part discusses the applicability of these tests to the range of neuromuscular disorders.     

Gadolinium-enhanced computed tomography angiography in multi-detector row computed tomography: initial observations

Rationale and Objectives. The feasibility of using gadolinium contrast medium for computed tomography angiography (CTA) in multi-detector row computed tomography and the effect of contrast medium dilution was investigated.Materials and Methods. Three pigs were each scanned in multiple sessions with injections of non-dilute and dilute contrast medium at a dose of 0.3 mmol/kg body weight. Non-spiral dynamic scanning at a fixed mid-abdominal aortic level and thoracoabdominal CTA were performed.Results. The magnitude of peak aortic enhancement was not significantly different between dilute and non-dilute contrast medium injections (P = .88), but the former showed earlier enhancement (mean of 2.3 seconds sooner, P < .01) than the latter. CT angiography with gadolinium contrast medium showed much lower enhancement than iodine contrast medium, but small vessels were readily identifiable.Conclusion. Gadolinium contrast medium combined with multi-detector row computed tomography may provide clinically useful CTA. Dilution of contrast medium shortens the enhancement time but has little effect on the magnitude.     

Renal artery aneurysms: diagnosis and surveillance with 3D contrast-enhanced magnetic resonance angiography

The use of contrast-enhanced magnetic resonance angiography (CE-MRA) in screening for suspected renovascular disease may result in increased detection of renal artery aneurysms. We report the CE-MRA findings at diagnosis and follow-up in nine hypertensive patients with unsuspected renal artery aneurysms. A search of renal CE-MRAs of suspected renal artery stenosis at two tertiary referral institutions over 5 1/2 years was performed. All patients underwent CE-MRA using a fast spoiled gradient echo technique (TR/TE/flip 5.1–6 ms/1.6 ms/40°), scan matrix 512×196–224, 1 excitation, FOV 400–450 mm×266–360 mm, 32–50 mm×1.5–2 mm interpolated slices. Gadolinium-enhanced 3D images were obtained during breath holding. Images were evaluated and post-processed on a workstation by a single operator. Nine patients with renal artery aneurysms out of a total of 912 cases were found, all involving the main artery or divisions proximal to the renal hilum. Renal arteries distal to the hilum were not consistently visualized. The aneurysm was bilobed in one patient, multilocular in another and unilocular in all others. Severe stenosis of the renal artery proximal to the aneurysm was present in two. Four patients underwent follow-up showing no change in aneurysm size. CE-MRA reliably identifies aneurysms involving the main renal arteries and proximal branches. Once diagnosed, CE-MRA offers a safe, non-invasive modality for surveillance of aneurysm if active intervention is not planned.