Bone cement with reduced proportion of monomer in total hip arthroplasty: Preclinical evaluation and randomized study of 47 cases with 5 years' follow-up

Bone cement with reduced amount of monomer and low curing temperature may improve implant fixation due to reduced toxicity. We analyzed the mechanical, chemical and thermal properties of such a cement (Cemex Rx) using Palacos R as control. The in vivo performance of the 2 cements was also evaluated in a prospective randomized study of 47 hips, where either of the cement types was used to fixate Lubinus SP2 prostheses with the stem made of titanium alloy. Cemex Rx had a reduced tensile strength, probably because this cement was manually mixed, as recommended by the manufacturer. A standardized laboratory test showed lower curing temperature for Cemex, but measurements at 37° and with prechilled Palacos R and Cemex Rx, as in clinical work, showed no difference. In the clinical study radiostereometric measurements of cup and stem migration showed similar values in the 2 groups up to 5 years after the operation. The cement mantle was stable in both groups, but the stems migrated similarly inside the cement mantle regardless of the type of cement used. Proximal wear was low (0.04-0.05 mm/year) and tended to be lower in the Cemex group (p = 0.02). Aluminum and vanadium levels in serum increased 5 years after the operation, but no difference was noted between the 2 groups. Collagen markers (PICP, ICTP) showed similar increases in bone turnover 6 weeks and 6 months after operation in both groups.     

CCN2 is transiently expressed by keratinocytes during re-epithelialization and regulates keratinocyte migration in vitro by the ras-MEK-ERK signaling pathway

Background

CCN2 (previously known as connective tissue growth factor) is a multifunctional matricellular protein that has numerous effects on cell life and cell interactions with the connective tissue. Although the importance of CCN2 for the fibrotic process in wound healing has been well studied, the involvement of CCN2 in keratinocyte function has not yet been explored. Therefore, the aim of the present study was to investigate the role of CCN2 in the epidermis during wound healing.

Materials and methods

Immunohistochemistry was done on sections from full-thickness porcine wounds. The effect of CCN2 on the migration of cultured human keratinocytes exposed to scratch wounds, the effect on phosphorylation of extracellular signal-related kinases (ERK), and the effect of adding inhibitors to the ERK/mitogen-activated protein kinase pathway to human keratinocytes were studied.

Results

The CCN2 protein was transiently expressed in vivo at the leading keratinocyte edge during re-epithelialization of full-thickness porcine wounds. In vitro, exogenous addition of CCN2 to human keratinocyte cultures regulated keratinocyte migration and resulted in phosphorylation of ERK. The addition of inhibitors of ERK/mitogen-activated protein kinase counteracted the effect of CCN2 on migration.

Conclusions

CCN2 was transiently expressed at the leading keratinocyte edge in vivo. The biologic importance of this was supported in vitro, because CCN2 regulated human keratinocyte migration through activation of the Ras-mitogen-activated protein kinase kinase-ERK signal transduction pathway.     

Renal transplant dysfunction--importance quantified in comparison with traditional risk factors for cardiovascular disease and mortality.

BACKGROUND: Renal transplant recipients (RTR) mainly die of premature cardiovascular disease. Traditional cardiovascular disease risk factors are prevalent in RTR. Additionally, non-traditional risk factors seem to contribute to the high risk. The impact of renal dysfunction was compared with traditional risk factors for cardiovascular morbidity and mortality in 1052 placebo-treated patients of the ALERT trial. METHODS: All patients were on cyclosporine-based immunosuppressive therapy, follow-up was 5-6 years and captured endpoints included cardiac death, non-cardiovascular death, all-cause mortality, major adverse cardiac event (MACE), non-fatal myocardial infarction (MI) and stroke. RESULTS: A calculated 84 micromol/l increase in serum creatinine was needed to double the risk for cardiac death, an increase of 104 micromol/l to double the risk for non-cardiovascular death and an increase of 92 micromol/l to double the risk for all-cause mortality. MACE risk was doubled if serum creatinine was elevated by 141 micromol/l, age was increased by 23 years, or LDL-cholesterol by 2 mmol/l. Diabetes increased the incidences of cardiac death, all-cause mortality, MACE, stroke and non-fatal MI. A serum creatinine increase of approximately 130 micromol/l, or approximately 20 years increase in age was calculated as similar in risk for cardiac death, all-cause mortality and MACE, and comparable to risk of diabetes in RTR. CONCLUSION: An increase in serum creatinine of 80-100 micromol/l doubles the risk for cardiac death, non-cardiovascular death and all-cause mortality in RTR. An increase of 130 micromol/l in serum creatinine or approximately 20 years increase in age is comparable to risk of diabetes.     

Increased incidence of life-threatening ventricular arrhythmias in implantable defibrillator patients after the World Trade Center attack

OBJECTIVES: This study was designed to evaluate whether the destruction of the World Trade Center (WTC) on September 11, 2001 (9/11), led to an increased frequency of ventricular arrhythmias among patients fitted with an implantable cardioverter-defibrillator (ICD). BACKGROUND: The WTC attack induced psychological distress. Because ICDs store all serious arrhythmias for months, the attack provided a unique opportunity to compare pre- and post-9/11 frequencies of potentially lethal arrhythmias among ICD patients. METHODS: Two hundred consecutive ICD patients who presented for regularly scheduled follow-up to six affiliated clinics were recruited into this observational study. The electrograms stored in the ICDs for the three months before 9/11 and 13 months thereafter were scrutinized in a blinded manner (relative to date) for all ventricular tachyarrhythmias (tachycardia or fibrillation) triggering ICD therapy. RESULTS: The frequency of tachyarrhythmias increased significantly for the 30 days post-9/11 (p = 0.004) relative to all other months between May 2001 and October 2002. In the 30 days post-9/11, 16 patients (8%) demonstrated tachyarrhythmias, compared with only seven (3.5%) in the preceding 30 days, representing a 2.3-fold increase in risk (95% confidence interval 1.1 to 4.9; p = 0.03). The first arrhythmic event did not occur for three days following 9/11, with events accumulating in a progressive non-clustered pattern. CONCLUSIONS: Ventricular arrhythmias increased by more than twofold among ICD patients following the WTC attack. The delay in onset and the non-clustered pattern of these events differ sharply from effects following other disasters, suggesting that subacute stress may have served to promote this arrhythmogenesis.     

Physical Functioning,Mental Health,and Quality of Life in Different Congenital Heart Defects: Comparative Analysis in 3538 Patients From 15 Countries

BackgroundWe compared physical functioning, mental health, and quality of life (QoL) of patients with different subtypes of congenital heart disease (CHD) in a large international sample and investigated the role of functional class in explaining the variance in outcomes across heart defects.MethodsIn the cross-sectional Assessment of Patterns of Patient-Reported Outcome in Adults with Congenital Heart Disease-International Study (APPROACH-IS), we enrolled 4028 adult patients with CHD from 15 countries. Diagnostic groups with at least 50 patients were included in these analyses, yielding a sample of 3538 patients (median age: 32 years; 52% women). Physical functioning, mental health, and QoL were measured with the SF-12 health status survey, Hospital Anxiety and Depression Scale (HADS), linear analog scale (LAS) and Satisfaction with Life Scale, respectively. Functional class was assessed using the patient-reported New York Heart Association (NYHA) class. Multivariable general linear mixed models were applied to assess the relationship between the type of CHD and patient-reported outcomes, adjusted for patient characteristics, and with country as random effect.ResultsPatients with coarctation of the aorta and those with isolated aortic valve disease reported the best physical functioning, mental health, and QoL. Patients with cyanotic heart disease or Eisenmenger syndrome had worst outcomes. The differences were statistically significant, above and beyond other patient characteristics. However, the explained variances were small (0.6% to 4.1%) and decreased further when functional status was added to the models (0.4% to 0.9%).ConclusionsSome types of CHD predict worse patient-reported outcomes. However, it appears that it is the functional status associated with the heart defect rather than the heart defect itself that shapes the outcomes.     

Granzyme D Is a Novel Murine Mast Cell Protease That Is Highly Induced by Multiple Pathways of Mast Cell Activation

Granzymes are serine proteases known mostly for their role in the induction of apoptosis. Granzymes A and B have been extensively studied, but relatively little is known about granzymes C to G and K to M. T cells, lymphohematopoietic stromal cells, and granulated metrial gland cells express granzyme D, but the function of granzyme D is unknown. Here we show that granzyme D is expressed by murine mast cells and that its level of expression correlates positively with the extent of mast cell maturation. Coculture of mast cells with live, Gram-positive bacteria caused a profound, Toll-like receptor 2 (TLR2)-dependent induction of granzyme D expression. Granzyme D expression was also induced by isolated bacterial cell wall components, including lipopolysaccharide (LPS) and peptidoglycan, and by stem cell factor, IgE receptor cross-linking, and calcium ionophore stimulation. Granzyme D was released into the medium in response to mast cell activation. Granzyme D induction was dependent on protein kinase C and nuclear factor of activated T cells (NFAT). Together, these findings identify granzyme D as a novel murine mast cell protease and implicate granzyme D in settings where mast cells are activated, such as bacterial infection and allergy.