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.     

Psychopathology and psychosocial adjustment in patients with HIV-associated lipodystrophy

ObjectiveTo study whether patients with HIV-1 associated lipodystrophy (LD) on highly active antiretroviral treatment (HAART) have more psychopathology and worse psychosocial adjustment than a similar group without this syndrome.MethodsIn a cross-sectional, observational study we compared 47 HIV-1 infected patients with LD (LD group) with 39 HIV-1 infected patients without LD (non-LD group). All participants were on HAART. The Beck Depression Inventory (BDI), the State and Trait Anxiety Inventory (STAI) and the Goldberg Health Questionnaire (GHQ-60) were administered. Levels of familial, work and social adjustment and adjustment to stressful events were evaluated in a semi-structured interview. Clinical information was extracted from the clinical records.ResultsIn the univariate analysis patients with LD showed higher state anxiety scores (p = 0.009) and worse work adjustment (p = 0.019) than those without LD. A total of 45.3% of LD patients scored above the cut-off point on the trait anxiety scale, and over 33.3% scored above the cut-off point on the BDI, GHQ and state anxiety scales. However, in multivariate analyses LD was not independently associated with psychopathology or with worse adjustment in the studied areas.ConclusionsThe finding that LD was not a predictor of greater psychopathology or worse psychosocial adjustment in HIV-1 infected patients, despite the high scores found, suggests that factors not taken into account in this study, such as LD severity and self-perception should have been included in the analysis. Further studies including a greater number of variables and a larger sample size will advance our understanding of this complex condition.     

Use of somatostatin analogue scintigraphy in the localization of recurrent medullary thyroid carcinoma

Detection of recurrence of medullary thyroid carcinoma (MTC) remains a diagnostic problem. Increased serum tumour marker levels frequently indicate recurrence while conventional imaging techniques (CIT) are non-diagnostic. In this study, we performed indium-111 octreotide scintigraphy and CIT in a series of 20 patients with MTC presenting with elevated serum tumour markers after surgery. ¹¹¹In-octreotide whole-body studies detected 15 pathological uptake foci in 11 of the 20 patients studied and CIT detected 17 lesions in 11 of the 20 patients. Ten patients underwent reoperation, five of them with positive ¹¹¹In-octreotide scintigraphy and CIT and two with positive isotopic exploration and negative CIT. Surgical findings demonstrated that the results of isotopic study and CIT had been false-positive for MTC in one case (sarcoidosis). The six patients with true-positive ¹¹¹In-octreotide studies had significantly higher basal calcitonin (CT) and carcinoembryonic antigen (CEA) levels than the patients with negative isotopic studies. The expression of somatostatin receptor (SSTR) subtypes by PC-PCR could be investigated in four cases with a positive isotopic study. Among the three cases with a true-positive study, SSTR2, the SSTR subtype that preferentially binds to the somatostatin analogue octreotide, was detected in two, SSTR5 was demonstrated in the three, and SSTR3 was detected in one. No subtype of SSTR was detected in the case with a final diagnosis of sarcoidosis. We conclude that ¹¹¹In-octreotide has limited sensitivity in detecting recurrence in patients with MTC, although its sensitivity may improve with high serum CT levels. This radionuclide imaging technique should be employed when conventional imaging techniques are negative or inconclusive or when the presence of somatostatin receptors may provide the basis for treatment with somatostatin analogues. Received 5 April and in revised form 27 July 1998     

Predictors of pleural malignancy in patients with pleural effusion undergoing thoracoscopy

STUDY OBJECTIVES: Thoracoscopic pleural biopsy is highly accurate in the diagnosis of pleural malignancy. However, no scientific evidence is currently available to guide the physician's decision as to when and in which patients with pleural effusion thoracoscopy is indicated. The application of predictive criteria of malignancy might improve the indication of thoracoscopy in patients with undiagnosed pleural effusion. METHODS: Prospective study of 93 patients referred for thoracoscopy at a tertiary hospital. Clinical variables were obtained prior to thoracoscopy by clinical history and review of previous data, patient interview, and physical examination. Radiologic variables were obtained by evaluation of chest radiograph and chest CT images by two independent readers. After thoracoscopy, all patients without a diagnosis were sent for long-term follow-up. RESULTS: Thoracoscopy demonstrated 94% sensitivity and 100% specificity in the diagnosis of pleural malignancy. Variables, which in a multivariate model are associated with pleural malignancy, include a symptomatic period > 1 month, absence of fever, blood-tinged pleural fluid, and chest CT scan findings suggestive of malignancy. Receiver operating characteristic analysis showed that the use of these four criteria offered adequate classification in 95% of patients. Twenty-eight patients had all four criteria, and all had malignancy; 21 patients had at most one criterion, and none had malignancy. CONCLUSION: Clinical and radiologic criteria of patients with pleural effusion permit different risk levels for pleural malignancy to be distinguished. Consequently, application of the four proposed criteria permits better indication of thoracoscopy in patients with undiagnosed pleural effusion.     

Hotspot of Crimean-Congo Hemorrhagic Fever Virus Seropositivity in Wildlife,Northeastern Spain

We conducted a serosurvey for Crimean-Congo hemorrhagic fever virus antibodies in various wildlife species in Catalonia, northeastern Spain. We detected high seroprevalence in southern Catalonia, close to the Ebro Delta wetland, a key stopover for birds migrating from Africa. Our findings could indicate that competent virus vectors are present in the region.