Efficacy of ciprofloxacin-releasing bioabsorbable osteoconductive bone defect filler for treatment of experimental osteomyelitis due to Staphylococcus aureus

The concept of local antibiotic delivery via biodegradable bone defect fillers with multifunctional properties for the treatment of bone infections is highly appealing. Fillers can be used to obliterate surgical dead space and to provide targeted local bactericidal concentrations in tissue for extended periods. Eventually, the osteoconductive component of the filler could guide the healing of the bone defect. The present experimental study was carried out to test this concept in a localized Staphylococcus aureus osteomyelitis model in the rabbit (n = 31). A metaphyseal defect of the tibia was filled with a block of bone cement, followed by insertion of a bacterial inoculum. After removal of the bone cement and surgical debridement at 2 weeks, the defect was filled with a ciprofloxacin-containing (7.6% +/- 0.1%, by weight) composite (treated-infection group) or with a composite without antibiotic (sham-treated group). Both a positive control group (untreated-infection group) and a negative control group were also produced. The treatment response, monitored by positron emission tomography (PET) with fluorine-18-labeled fluorodeoxyglucose ([18F]FDG) at 3 and 6 weeks, showed rapidly decreasing amounts of [18F]FDG uptake in the treated-infection group (P = 0.001 compared with the results for the untreated-infection group at 6 weeks). The bacteriological analysis confirmed the eradication of the bone pathogen in the treated-infection group. However, three animals had culture-positive soft tissue infections. All animals in the sham-treated and untreated-infection groups had culture-positive bone infections with typical radiographic changes of osteomyelitis. Histomorphometry, peripheral quantitative computed tomography, and backscattered electron imaging of scanning electron microscopy images verified the osteoconductive properties of the bioactive glass microspheres within the composite. The median bone ciprofloxacin concentrations were 1.2 and 2.1 microg/g at two anatomic locations of the tibia. This is the first report to show the value of [18F]FDG PET for quantitative monitoring of the treatment response in bone infections. The collaborative results of bacteriologic and [18F-FDG] PET studies showed that use of the multifunctional composite was successful for eradication of the S. aureus pathogen from bone.     

Vasodilation of epicardial coronary artery can be measured with transthoracic echocardiography

Transthoracic Doppler echocardiography (TTE) has been introduced as a noninvasive tool to measure coronary flow velocity reserve (CFVR). Velocity measurement, however, fails to take into account epicardial coronary artery vasodilation during hyperemia and this may cause underestimation of CFVR measurements. Therefore, we sought to determine whether the vasodilation of epicardial coronary artery can be measured during cold pressor test (CPT) and adenosine infusion simultaneously with the flow velocity measurement using TTE. We studied 41 healthy nonsmoking men with a linear high-frequency 8.0-MHz transducer. The CPT and adenosine infusion dilated the diameter of the distal left anterior descending coronary artery (LAD) from 1.4 +/- 0.4 mm to 1.5 +/- 0.4 mm (14 +/- 13%, p < 0.01) and from 1.4 +/- 0.4 mm to 1.8 +/- 0.5 mm (31 +/- 19%, p < 0.01), respectively. The CPT increased flow velocity and calculated coronary blood flow rate (velocity time integral x cross-sectional area) from 0.23 +/- 0.05 m/s to 0.36 +/- 0.13 m/s (31 +/- 34%, p < 0.01) and from 8.1 +/- 4.2 mL/min to 11.4 +/- 6.0 mL/min (47 +/- 51%, p < 0.01). CFVR and calculated coronary blood flow rate reserve were 3.9 +/- 1.0 and 6.0 +/- 1.9, respectively. In Bland-Altman analysis, velocity measurements underestimated the vasodilation response of the CPT and adenosine compared with the measurements where epicardial diameter dilation was taken into account. Intra- and interobserver variability of diameter measurements was low (coefficient of variation [CV] 2.6 to 6.5%). Day-to-day, within-day and intersonographer variabilities were of similar magnitude (CV 4.6 to 8.2%), suggesting good reproducibility. This study demonstrates that TTE can be used to assess changes in both epicardial coronary artery diameter and flow velocity simultaneously in the distal LAD artery.     

Effects of common polymorphisms in the alpha1A-, alpha2B-, beta1- and beta2-adrenoreceptors on haemodynamic responses to adrenaline

Common naturally occurring polymorphisms have been identified in the coding regions of the alpha(1A)-, alpha(2B)-, beta(1)- and beta(2)-adrenoceptor (AR) genes [alpha(1A)-AR R492C, alpha(2B)-AR insertion/deletion (I/D), beta(1)-AR R389G, beta(2)-AR G16R and beta(2)-AR Q27E] and are associated with modified in vivo and in vitro functionality. We tested their possible effects on the haemodynamic responses to intravenous adrenaline (20, 40, 80 and 160 ng/kg of body weight per min; 5 min for each infusion rate) before and after beta-blockade (propranolol) in 16 young healthy men. We monitored changes in heart rate, blood pressure (BP), ECG, coronary flow velocity and plasma adrenaline and noradrenaline. The Cys/Cys (CC) genotype of the alpha(1A)-AR R492C polymorphism was associated with a longer ECG PR interval before and during the adrenaline infusions. The deletion/deletion (D/D) genotype of the alpha(2B)-AR I/D polymorphism was associated with blunted coronary blood flow increases during the adrenaline infusion before beta-blockade. The beta(1)-AR R389G polymorphism was not associated with modified responses to infused adrenaline. Subjects carrying the Gly/Gly (GG) genotype of the beta(2)-AR G16R polymorphism demonstrated increases in diastolic BP upon adrenaline infusion, whereas diastolic BP was decreased in the other genotype groups. These results suggest that, upon acute adrenaline infusion, the alpha(2B)-AR D/D genotype confers increased vasoconstriction and that the beta(2)-AR GG genotype confers reduced vasodilatation.     

Radiofrequency induced thermotherapy: an alternative palliative treatment modality in head and neck cancer

Bipolar radiofrequency induced thermotherapy (RFITT) is a minimally invasive electrosurgical technique characterized by a precise controllable effect in the tissue. It has demonstrable efficacy, safety and reproducibility in the management of solid malignancies. Our aim was to assess the morbidity and efficacy of RFITT as a palliative treatment of head and neck cancer. Prospective, non-randomized case series and analysis. After evaluation by the multidisciplinary Head and Neck Tumour Board at Helsinki University Central Hospital, Finland, 12 consecutive patients with a head and neck cancer without curative treatment possibilities were enrolled into the study. Five patients had pharyngeal carcinomas, one had an unknown primary tumour growing through the skin on the neck, two had a recurrent malignant melanoma originating from the maxillary sinuses, one had a carcinoma of the tongue, two had laryngeal carcinomas, and one had a recurrent adenoid cystic carcinoma of the parotid gland. RFITT was performed with a CelonLabPrecision® generator using appropriate electrodes. The treatment was administered under local or general anaesthesia. The subjective morbidity of the treatment was evaluated. The response to the treatment was assessed clinically and with radiological imaging when feasible. All but two of the patients received palliation to their disease. RFITT induced clinically a partial response in ten patients, and there were radiological detectable changes. There were no treatment related complications, and the patients tolerated the treatment well. RFITT in head and neck cancer patients is easy to perform, well tolerated, and induces reduction in the tumour mass. Continuous evaluation of RFITT treatment modality is warranted in selected palliative care patients.     

Deficient language acquisition in children with single suture craniosynostosis and deformational posterior plagiocephaly

Purpose  

This study examined early language acquisition in children with single suture craniosynostosis (SSC) and in children with deformational posterior plagiocephaly. Our purpose was to determine whether infants with SSC have normal language acquisition at the age of 3 years, and whether infants with deformational posterior plagiocephaly demonstrate parallel development when compared with children with SSC.     

Increased circulating concentrations and augmented myocardial extraction of osteoprotegerin in heart failure due to left ventricular pressure overload

BACKGROUND: Osteoprotegerin (OPG) and the receptor activator of nuclear factor-kappaB ligand (RANKL), two cytokines regulating bone remodeling, have recently been raised as potential pathogenetic factors in cardiovascular diseases. We have studied circulating and myocardial OPG and RANKL in patients having severe aortic stenosis (AS) with or without heart failure (HF). METHODS: We studied 131 adults with AS. Blood was sampled from the aortic root, coronary sinus, and femoral vein at cardiac catheterization. LV myocardial biopsies were taken at surgery. Plasma OPG and soluble (s)RANKL were analyzed by ELISA, and myocardial OPG and RANKL by RT-PCR and immunohistochemistry. RESULTS: Circulating OPG was elevated in AS patients with HF, the association being independent of age, sex, and presence of coronary artery disease (beta=0.17, p=0.033). Elevated plasma OPG decreased after valve replacement in patients with preoperative HF (p=0.0005). Relative to its concentration in the aortic root, plasma OPG was reduced in the coronary sinus (p<0.05) and in the femoral vein (p<0.001), these arteriovenous gradients being accentuated in HF (p=0.003). CONCLUSIONS: HF due to LV pressure overload in AS increases circulating OPG and augments OPG extraction by the heart and peripheral tissues. OPG may be involved in the pathogenesis of HF and could serve as a useful biomarker in HF due to LV pressure overload.     

Cephalometric pharyngeal changes after Le Fort I osteotomy in patients with unilateral cleft lip and palate

Pharyngeal changes after Le Fort I osteotomy were evaluated cephalometrically in 37 patients (27 M, 10 F; mean age 23.8 years) with unilateral cleft lip and palate (UCLP). Seven patients had previously undergone velopharyngeal (VPP) flap surgery to improve speech. One year postoperatively the patients without previous VPP showed a significant change (55%-85% of the surgical change) in the upper and lower sagittal depth of the nasopharyngeal airway, but not in the depth of oropharyngeal airway, length of soft palate, or position of hyoid bone. No significant changes were observed between 6 months and 1 year postoperatively. Mean surgical horizontal advancement was 4.7 mm and the mean vertical lengthening 4.7 mm anteriorly and 1 mm posteriorly. There was a correlation between the amount of horizontal advancement and the amount of change in the nasopharyngeal airway. The patients with previous VPP showed significant postoperative change (85% of the surgical change) only in the lower nasopharyngeal airway, although their surgical advancement was similar to that without previous VPP. Patients with previous VPP showed significantly smaller depths of upper nasopharyngeal airway postoperatively than the patients without previous VPP. Five patients (13%) needed VPP after the osteotomy. There was no difference in the nasopharyngeal airway in the patients with VPP after the osteotomy when compared to those without, but they seemed to have shortest maxillary lengths and largest mean surgical changes vertically both anteriorly (5.5 mm) and posteriorly (2.3 mm). Moderate maxillary advancement in UCLP patients results in significant changes in the nasopharyngeal airway.     

The meaning of the working cooperative for persons with long-term mental illness: a phenomenological study.

OBJECTIVE: The objective of this phenomenological study was to understand the meanings of the lived experiences of persons with long-term mental illness at a social working cooperative. METHOD: Eighteen participants were interviewed either two or three times while participating in a working cooperative in a community psychosocial rehabilitation program. Data were analyzed and interpreted using the Empirical, Phenomenological, Psychological (EPP) method (Karlsson, 1993). RESULTS: The findings revealed a meaning-structure consisting of one main constituent that characterized the cooperative as a normalizing life-world. Three phases contributed to the normalization process. In the first phase the participants experienced a shift from an unsatisfying occupational context to an enriching occupational life-world. In the second phase participants had the possibility to satisfy some of their occupational and social needs. During this phase, experiences of being productive and needed, commitment to others, development of their skills, and competence in work tasks and social activities were expressed, all of which contributed to personal growth and a more positive view of self. In the third phase, the meaning of the cooperative changed for some participants, who expressed this through their readiness to leave and take a further step into the life-world outside the cooperative. CONCLUSION: The study emphasizes that the cooperative is an important alternative to employment for participants with severe mental illness who do not have the capacity to be employed in the community or who do not want to leave the life-world of the cooperative that gives them pride, joy, and satisfaction.     

Transcardiac gradients of N-terminal B-type natriuretic peptide in aortic valve stenosis

BACKGROUND: Plasma B-type natriuretic peptide (BNP), as well as the N-terminal part of the prohormone (Nt-BNP), are frequently elevated in aortic valve stenosis (AS). Yet, their release from the heart into the circulation has never been directly studied in AS. AIM: To assess the release of Nt-BNP in AS with focus on the identification of its main determinants. METHODS: We studied 49 adult patients undergoing preoperative cardiac catheterization for isolated AS. Blood was sampled from the aortic root and the coronary sinus for Nt-BNP determination by immunoassay. RESULTS: The mean (+/-S.E.) transcardiac Nt-BNP step-up averaged 79+/-53 pmol/l in 11 control patients free of structural heart disease, 75+/-32 pmol/l in 31 AS patients free of heart failure (HF), 236+/-62 pmol/l in 8 AS patients with diastolic HF (ejection fraction > or = 50%, pulmonary wedge pressure > 14 mm Hg) and 469+/-66 pmol/l in 7 AS patients with systolic HF (ejection fraction < 50%, wedge pressure > 14 mm Hg) (p<0.001). The transcardiac Nt-BNP gradient was independently associated with left ventricular (LV) end-diastolic pressure (beta=0.47, p<0.001) and ejection fraction (beta=-0.29, p<0.019) and with co-existent coronary artery disease (beta=0.23, p=0.050). CONCLUSION: LV diastolic and systolic dysfunction along with coronary artery disease are likely to be the key determinants of cardiac Nt-BNP release in AS. The transcardiac Nt-BNP gradient increases on average three-fold with the development of diastolic HF and six-fold in systolic HF.