Influence of exercise rehabilitation on myocardial perfusion and sympathetic heart innervation in ischaemic heart disease

Exercise rehabilitation improves the clinical status in ischaemic heart disease. The purpose of this study was to assess the influence of exercise rehabilitation on myocardial perfusion and sympathetic heart innervation. Sixteen patients with ischaemic heart disease and previous myocardial infarction were investigated by means of exercise/rest tetrofosmin and metaiodobenzylguanidine (MIBG) exercise/rest single-photon emission tomography (SPET) studies, before and 6 months after starting an exercise rehabilitation programme. Tomograms were divided into 15 segments, and these were grouped into five myocardial anatomical regions. Regional uptake of both tracerswas quantified and expressed as a percentage of maximumpeak activity. The percentage ≤55% was chosen to evaluate defect size, and the results were expressed as a percentage of left ventricular mass. Areas with perfused and denervated myocardium and areas with ischaemic myocardium were calculated. In addition, regions with <75% of peak activity in the exercise perfusion study at baseline were divided into two groups according to whether there was an increase in peak activity of >10% (representing reversible regional defects) or an increase of <10% (representing fixed regional defects) in the rest study. These percentages were compared with the percentages obtained in the innervation study, and with the percentages obtained in exercise/rest perfusion and innervation studies performed 6 months after starting rehabilitation. Myocardial perfusion defects were significantly smaller than myocardial innervation defects before and 6 months after starting exercise rehabilitation. The area of ischaemia 6 months after starting exercise rehabilitation was significantly smaller than that before rehabilitation (0.31%± 1.4% vs 1.4%±1.6%, P<0.01). The size of innervation defects and the area of perfused and denervated myocardium did not show significant differences between the two studies performed before and 6 months after starting exercise rehabilitation. In reversible regional defects the percentage of peak activity was significantly increased 6 months after starting exercise rehabilitation in exercise and rest studies (P<0.001), while in fixed regional defects it was significantly increased only in exercise studies (P<0.001). There was no significant change in the regional MIBG percentages. We conclude that in ischaemic heart disease, exercise rehabilitation over a period of 6 months improves myocardial perfusion, but does not cause changes in sympathetic myocardial innervation. Received 12 August and in revised form 17 November 1999     

Aortic valve morphology definition with transthoracic combined with transesophageal echocardiography in a population with high prevalence of bicuspid aortic valve

Objective:To assess the utility of transthoracic echocardiography (TTE) with second harmonic combined with transesophageal echocardiography (TEE) in defining aortic valve morphology in a subset of patients with a high prevalence of bicuspid aortic valve. Methods and Materials: Patients (n=174) with dilated aortic root were consecutively evaluated using, initially, TTE. The aortic valve structure was assigned as tricuspid, bicuspid or undefined. In those assigned as bicuspid or undefined, TEE was performed. Other factors that could affect valve morphology assignment were recorded and evaluated in multivariate analysis. Results: TTE was able to characterise 89% of the tricuspid valves and 56% of the bicuspid. Bicuspid structure was the only variable that, in the multivariate analysis, was related to the inability to definitively assign aortic valve morphology (OR=0.13). TEE was performed in 59 patients and the morphology was definitively assigned in 56 of them (95%). TEE diagnosed 15 bicuspid valves in addition to confirming the 17 identified by TTE. Overall, using TTE combined with TEE we were able to correctly assign valvular morphology in 98% of patients. Conclusion: In a subset of patients with a high prevalence of bicuspid aortic valve, combination of TTE and TEE should be considered to define aortic valve morphology. TEE identifies an important number of patients with BAV.     

Rat CCl4‐induced cirrhosis plus total portal vein ligation: a new model for the study of hyperammonaemia and brain oedema

Introduction: Animal models used to study hyperammonaemic disorders related to chronic liver disease are unsatisfactory. These animals only develop hyperammonaemia and brain oedema when fed with diets supplemented with amonium acetate. Aim: To develop a novel experimental model of hyperammonaemia and brain oedema in CCl₄‐induced cirrhosis in rats. Methods: Four groups were studied: rats with sham intervention (S), rats with total portal vein ligation (TPVL), cirrhotic rats (LC), and cirrhotic rats with TPVL (LC+TPVL). When ascites was diagnosed, oral glutamine challenge (OGC) test was performed. Blood, liver, lungs and brain samples were collected to quantify liver function parameters, plasmatic and cerebral ammonia, endotoxaemia, liver and brain histology, brain oedema and portosystemic shunting degree. Results: LC+TPVL rats showed a significant increase in portosystemic shunting when compared with LC group and a significant derangement in liver function when compared with TPVL group. These alterations resulted in a significant increase in plasmatic and brain ammonia concentrations and a higher plasmatic endotoxaemia as compared with others. Similarly, the area under OGC curve was significantly increased in LC+TPVL group as compared with the others, and correlates with portal shunting. Low‐grade brain oedema was only observed in LC+TPVL group. All cirrhotic groups showed liver regeneration nodules and type‐II Alzheimer astrocytes Conclusion: LC+TPVL reproduce the main alterations – portosystemic shunting, plasmatic and cerebral hyperammonaemia and low‐grade brain oedema – observed in cirrhotic patients with hepatic encephalopathy.     

The use of taxanes in the neoadjuvant treatment of breast cancer: a review of randomized phase II/III trials

This review examines all randomized studies that evaluated the role of taxanes in the neoadjuvant treatment of breast cancer and have reported results in terms of efficacy and tolerance. The primary objective of this review was to evaluate whether, at this point in time, there is sufficient evidence to support the routine use of taxanes in the neoadjuvant treatment of breast cancer. Other objectives were to determine the optimal schedule in which to administer taxanes and anthracyclines and whether the addition of other antitumor drugs improves the efficacy of these anthracycline/taxane-based schedules. A literature search revealed 9 major randomized clinical trials published to date. To facilitate analysis, they were classified according to their protocol design. Five trials evaluated the effect of the addition of a taxane to an anthracycline-based schedule, either concomitantly or sequentially. The remaining 4 trials contained taxanes in both treatment arms in an attempt to optimize the administration schedule of anthracyclines and taxanes, or to improve efficacy by adding a further antitumor drug. This type of analysis has provided the opportunity to draw some conclusions regarding the optimal use of taxanes.     

Diagnostic, prognostic and pathogenic value of the direct immunofluorescence test in cutaneous leukocytoclastic vasculitis

BACKGROUND: No precise studies have been performed on cutaneous leukocytoclastic vasculitis (LV) to establish whether it is better to obtain a skin biopsy from lesional or from perilesional skin for direct immunofluorescence (DIF). There is no agreement on the immunoglobulins most frequently detected and the value of DIF for the classification of cutaneous vasculitis. METHODS: A prospective study of DIF in lesional and perilesional skin was performed in 50 leukocytoclastic vasculitis patients and 15 nonvasculitis patients. RESULTS: We detected a higher level of positivity in involved skin than in uninvolved skin for IgG, IgA, IgM, C3 and fibrinogen but not for C1q. In vasculitic patients, IgA was the immunoglobulin most frequently detected in lesional (82%) and perilesional skin (68%), followed by IgM (56 and 34%, respectively) and IgG (20 and 8%, respectively). Only IgA deposits were associated with the diagnosis of vasculitis, with a sensitivity of 82% in lesional and 68% in perilesional skin, and with a specificity of 73 and 66.7%, respectively. The presence of IgA in lesional skin was associated with renal involvement but there was no association with severity. The presence of IgG or IgM, or the absence of IgA in perilesional skin was related to the presence of cryoglobulins. The absence of IgA in lesional and perilesional skin was also related to hepatitis C virus infection. CONCLUSIONS: DIF findings in involved skin are more closely related to the diagnosis of vasculitis and can give more information about overall renal involvement than findings in uninvolved skin. However, findings in uninvolved skin are more closely related to the pathogenic factors that trigger the development of vasculitis.     

Induction of tumor NK-cell immunity by anti-CD69 antibody therapy

The leukocyte activation marker CD69 is a novel regulator of the immune response, modulating the production of cytokines including transforming growth factor-beta (TGF-beta). We have generated an antimurine CD69 monoclonal antibody (mAb), CD69.2.2, which down-regulates CD69 expression in vivo but does not deplete CD69-expressing cells. Therapeutic administration of CD69.2.2 to wild-type mice induces significant natural killer (NK) cell-dependent antitumor responses to major histocompatibility complex (MHC) class I low RMA-S lymphomas and to RM-1 prostatic carcinoma lung metastases. These in vivo antitumor responses are comparable to those seen in CD69(-/-) mice. Enhanced host NK cytotoxic activity correlates with a reduction in NK-cell TGF-beta production and is independent of tumor priming. In vitro studies demonstrate the novel ability of anti-CD69 mAbs to activate resting NK cells in an Fc receptor-independent manner, resulting in a substantial increase in both NK-cell cytolytic activity and interferon gamma (IFNgamma) production. Modulation of the innate immune system with monoclonal antibodies to host CD69 thus provides a novel means to antagonize tumor growth and metastasis.     

Effectiveness of tranexamic acid in revision total knee arthroplasty

The effectiveness of Tranexamic Acid (TXA, antifibrinolytic drug) in reducing allogeneic blood transfusion requirements has not been tested in revision total knee arthroplasty. The aim of this study was to assess the effectiveness of TXA after two intravenous doses of 1 g each. Between April 2006 and February 2010, 68 consecutive patients (19 male, 49 female) of 74 +/- 6 [m +/- SD] years of age were included and divided into three groups: control (28 patients), in which TXA was not administered but was not contraindicated; TXA (19 patients) who received TXA, and NO-TXA (21 patients), who were not administered TXA because of a contraindication. The proportions of patients transfused were 54%, 32% and 62% respectively in the control, TXA and NO-TXA group; the median numbers of RBC units transfused were respectively 2 [range: 1-4], 2 [range: 2-2] and 2.5 [range: 1-5], (p = 0.057). Mean total estimated blood loss was 1693 mL (SD: 689) in the control group, 1196 mL (SD: 665) in the TXA group and 2454 mL (SD: 2166) in the NO-TXA group, (p = 0.015). No adverse events were reported. TXA administration appeared as an effective and safe means of reducing blood transfusion requirements and blood loss in revision total knee arthroplasty.     

Impact of hip anatomical variations on the cartilage stress: A finite element analysis towards the biomechanical exploration of the factors that may explain primary hip arthritis in morphologically normal subjects

Background

Hip arthritis is a pathology linked to hip-cartilage degeneration. Although the etiology of this disease is not well defined, it is known that age is a determinant risk factor. However, hip arthritis in young patients could be largely promoted by biomechanical factors. The objective of this paper is to analyze the impact of some normal anatomical variations on the cartilage stress distributions numerically predicted at the hip joint during walking.

Methods

A three-dimensional finite element model of the femur and the pelvis with the most relevant axial components of muscle forces was used to simulate normal walking activity. The hip anatomical condition was defined by: neck shaft angle, femoral anteversion angle, and acetabular anteversion angle with a range of 110–130°, 0–20°, and 0–20°, respectively. The direct boundary method was used to simulate the hip contact.

Findings

The hydrostatic stress found at the cartilage and labrum showed that a ± 10° variation with respect to the reference brings significant differences between the anatomic models. Acetabular anteversion angle of 0° and femoral anteversion angle of 0° were the most affected anatomical conditions with values of hydrostatic stress in the cartilage near 5 MPa under compression.

Interpretation

Cartilage stresses and contact areas were equivalent to the results found in literature and the most critical anatomical regions in terms of tissue loads were in a good accordance with clinical evidence. Altogether, results showed that decreasing femoral or acetabular anteversion angles isolatedly causes a dramatic increase in cartilage loads.