Joint replacement and human immunodeficiency virus

The incidence of human immunodeficiency virus(HIV)-infected cases that need total joint replacement(TJR) is generally rising. On the other hand, modern management of HIV-infected cases has enabled them to achieve longevity while increasing the need for arthroplasty procedures due to the augmented degenerative joint disease and fragility fractures, and the risk of osteonecrosis. Although initial investigations on joint replacement in HIV-infected cases showed a high risk of complications, the rec...     

Termination of professional responsibility: Exploring the process of discharging patients with heart failure from hospitals

Hekmatpou D, Mohammadi E, Ahmadi F, Arefi SH. International Journal of Nursing Practice 2010; 16 : 389–396
Termination of professional responsibility: Exploring the process of discharging patients with heart failure from hospitals Despite the emphasized importance of the discharge process for patients with heart failure, this process is not taken as seriously as it should be. The objective of this qualitative study is to explore the concept of discharge and its associated factors in 42 experienced patients, family members, nurses and cardiologists at two educational hospitals in Tehran, Iran. The content analysis of the data indicates that the participants consider hospital discharge as the termination of professional responsibility on the part of physicians and nurses as far as health‐care support is involved. Three themes were identified as factors related to the treating team, health‐care system and patients and their families. Adverse outcomes of inappropriate discharge planning which manifested as incompliance with ‘diet and medical regimen’ and lack of lifestyle modification were also noted. It seems proper to try and change the attitude of physicians and nurses towards the concept of discharge, and raise their sensitivity to organizing and executing discharge plans. It is also recommended that postdischarge care should be established.     

Langerhans Cell Histiocytosis of the Lung and Thyroid, Co-Existing with Papillary Thyroid Cancer

A 24-year-old man presented to our center with a huge goiter compressing his airway. He had a previous diagnosis of Langerhans cell histiocytosis (LCH) of the lung. Core needle biopsy was consistent with histiocytosis. Thyroidectomy was performed. A very invasive mass was encountered at the time of surgery. Histopathology result was consistent with an invasive papillary cancer of thyroid co-occurring with LCH. Although association of LCH with different malignancies has been reported, co-existing invasive papillary thyroid cancer and LCH is a rare combination.     

SecA2-dependent secretion of autolytic enzymes promotes Listeria monocytogenes pathogenesis

Pathogenic bacteria secrete proteins that promote invasion of host tissues and resistance to immune responses. However, secretion mechanisms that contribute to the enormous morbidity and mortality of Gram-positive bacteria are largely undefined. An auxiliary protein secretion system (SecA2) has recently emerged in Listeria monocytogenes and eight other Gram-positive pathogens. Here, a proteomics approach identified seventeen SecA2-dependent secreted and surface proteins of L. monocytogenes, the two most abundant of which [the p60 and N-acetylmuramidase (NamA) autolysins] hydrolyze bacterial peptidoglycan (PGN) and contribute to host colonization. SecA2-deficient (DeltaSecA2) bacteria were rapidly cleared after systemic infection of murine hosts, and in cultured cells showed reduced cell-cell spread. p60 or NamA deficiencies (Deltap60 and DeltaNamA) caused intermediate reductions in bacterial virulence in vivo, yet showed no defect for infection of cultured cells. Restoration of virulence in Deltap60 bacteria required full-length p60 with an intact catalytic domain, suggesting that PGN hydrolysis by p60 is crucial for L. monocytogenes virulence. Coordinated PGN hydrolysis by p60 and NamA activities is predicted to generate a muramyl glycopeptide, glucosaminylmuramyl dipeptide (GMDP), which is known to modify host inflammatory responses. Thus, SecA2-dependent secretion may promote release of muramyl peptides that subvert host pattern recognition.     

Intermediate follow-up of a composite stentless porcine valved conduit of bovine pericardium in the pulmonary circulation

BACKGROUND: In the pediatric population, glutaraldehyde-preserved bovine pericardium conduit containing a stentless porcine valve has been proposed as an alternative to homografts for right ventricular outflow tract reconstruction. METHODS: Between June 1996 and March 2000, a total of 55 patients, 20 with truncus arteriosus, 21 with pulmonary atresia with ventricular septal defect, and 14 with miscellaneous defects, received this conduit. Median age at implantation was 3.4 months (range, 3 days to 19 years), and 27 patients (50%) were less than 3 months old. Clinical outcome, echocardiographic data, and pathologic analysis were recorded. End points for conduit failure were conduit replacement or dilation. A mean follow-up of 27 months (range, 2 to 46 months) was available for 47 survivors. RESULTS: Procedure for conduit obstruction was required in 13 patients. The most common procedure was operation, and all but 3 patients had an unsuccessful balloon angioplasty before reoperation. Actuarial freedom from conduit dilation or reoperation was 93.6% (95% confidence limits, 82% to 99%), 81.9% (95% confidence limits, 64% to 91%), 77.8% (95% confidence limits, 39% to 78%), and 64.3% (95% confidence limits, 26% to 73%) at 1, 2, 3, and 4 postoperative years, respectively. Univariate analysis identified small conduit size as a risk factor for conduit obstruction. CONCLUSIONS: Although this new conduit was not free from progressive obstruction, our clinical results (easy to work and good valvular function) and the availability in small sizes encouraged us to use it as an alternative to small-size homografts when those were not available.     

Interaction of high concentrations of riluzole with recombinant skeletal muscle sodium channels and adult-type nicotinic receptor channels

Riluzole is a neuroprotective drug that modulates glutamergic transmission but also blocks the inactivated state of voltage-gated neuronal sodium channels at very low concentrations (about 0.1 microM). After nausea, the most common adverse effect of riluzole is asthenia, which could be due to a block of muscle sodium channels or acetylcholine receptor channels. Using the patch-clamp technique, we applied riluzole on recombinant voltage-gated skeletal muscle sodium and adult nicotinic acetylcholine receptor channels expressed in a mammalian cell line (HEK 293). Riluzole blocked the inactivated state of voltage-gated skeletal muscle sodium channels, shifting the midpoint of the steady-state inactivation curve to more negative potentials, but only in comparatively high concentrations (> or = 0.1 mM). At these concentrations, riluzole also caused an open-channel block at acetylcholine receptor channels. We conclude that riluzole has only a mild blocking effect on the inactivated state of voltage-gated skeletal muscle sodium channels and nicotinic acetylcholine receptor channels. As the plasma concentration of riluzole in amyotrophic lateral sclerosis (ALS) patients approximates 2 microM, it seems unlikely that asthenia is caused by a block of skeletal muscle sodium channels or acetylcholine receptor channels by riluzole.     

SU6668 is a potent antiangiogenic and antitumor agent that induces regression of established tumors

Vascular endothelial growth factor, fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF) and their cognate receptor tyrosine kinases are strongly implicated in angiogenesis associated with solid tumors. Using rational drug design coupled with traditional screening technologies, we have discovered SU6668, a novel inhibitor of these receptors. Biochemical kinetic studies using isolated Flk-1, FGF receptor 1, and PDGF receptor beta kinases revealed that SU6668 has competitive inhibitory properties with respect to ATP. Cocrystallographic studies of SU6668 in the catalytic domain of FGF receptor 1 substantiated the adenine mimetic properties of its oxindole core. Molecular modeling of SU6668 in the ATP binding pockets of the FIk-1/KDR and PDGF receptor kinases provided insight to explain the relative potency and selectivity of SU6668 for these receptors. In cellular systems, SU6668 inhibited receptor tyrosine phosphorylation and mitogenesis after stimulation of cells by appropriate ligands. Oral or i.p. administration of SU6668 in athymic mice resulted in significant growth inhibition of a diverse panel of human tumor xenografts of glioma, melanoma, lung, colon, ovarian, and epidermoid origin. Furthermore, intravital multifluorescence videomicroscopy of C6 glioma xenografts in the dorsal skinfold chamber model revealed that SU6668 treatment suppressed tumor angiogenesis. Finally, SU6668 treatment induced striking regression of large established human tumor xenografts. Investigations of SU6668 activity in cancer patients are ongoing in Phase I clinical trials.     

Intracardiac ultrasound detection of thrombus on transseptal sheath: incidence, treatment, and prevention

BACKGROUND: Transseptal (TS) catheterization is used for left atrial (LA) ablation procedures and a major risk is thromboembolism. The purpose of this study was to assess (1) the value of intracardiac ultrasound (ICUS) monitoring during LA ablation procedures, and (2) a new technique to reduce the risk of thrombus formation. METHODS AND RESULTS: One hundred and eighty consecutive patients underwent TS catheterization under ICUS guidance with two sheaths for atrial fibrillation ablation and one for other LA procedures. Group I included the initial 90 patients in whom TS sheaths were flushed with a standard 2 U/cc concentration of heparin; group II consisted of the next 90 patients in whom sheaths were flushed with 1,000 U/cc concentration. All patients received bolus and infusion of heparin to maintain ACT between 250-300 seconds. ICUS was monitored throughout. In group I, echodense material at the tip of the sheath consistent with thrombus was observed on ICUS in 8 of 90 patients (9%) within 5-15 minutes of entering the LA. In group II, only 1 of 90 patient (1%) demonstrated thrombus (P < 0.001). There were no significant clinical differences in group I patients with and without thrombus. In all nine patients, the clot was removed with vigorous aspiration. No patients suffered a neurological event. CONCLUSION: Thrombus formation on TS sheath, detected by ICUS, may be more common than expected despite adequate anticoagulation. Using a higher concentration of heparin for the TS system before deployment reduced the risk. The thrombus was retrieved with aspiration without the need to abort the procedure.