Inactivation of C3H 10T1/2 cells by monoenergetic high LET alpha-particles.

Inactivation of mouse C3H 10T1/2 cells in plateau-phase (7.8 x 10(4) cells/cm2) was studied by using alpha-particles from the irradiation facility installed for radiobiological experiments at the 3 MV Tandem accelerator, University of Naples. Silicon detectors and CR39 plastic track detectors were employed for dosimetric purposes. The cells were exposed to high LET monoenergetic alpha-particles (energy of 1.8 MeV at the centre of the cell nucleus, track-averaged LET of 177 keV/micron and dose-rate of 1.1 Gy/min) and low-LET 80 kVp X-rays. The X-ray survival curve showed a significant shoulder (alpha/beta = 9 Gy) while the survival curve for alpha-particles was close to exponential. The mean lethal dose of alpha-particles was 0.77 +/- 0.02 Gy and the RBE was 5.2 at 80% survival and 3.0 at 5% survival. Survival of exponentially growing cells (2 x 10(4) cells/cm2) following irradiation with the alpha-particle beam is also reported. The nuclear areas of 10T1/2 cells were measured as 299 +/- 9 micron 2 and 250 +/- 8 micron 2 for cells in log phase and plateau phase, respectively. The inactivation cross-section, obtained from the mean lethal dose, was 34 micron 2 and 37 micron 2 for cells in log phase and plateau phase, respectively. These values appear to be the maximum measured values for the inactivation cross-section of 10T1/2 cells as a function of the alpha-particle LET. This saturation cross-section is very similar to the saturation values reported in the literature for other mammalian cell lines.     

Normal splenic function in children with the nephrotic syndrome

Children with the idiopathic nephrotic syndrome (NS) are known to be susceptible to bacterial infections. A recent report suggested that splenic hypofunction may be responsible for this immunological defect. We assessed splenic function by counting the circulating pocked red blood cells (PkRBCs) using interference phase contrast microscopy. PkRBCs are removed by the spleen, so that normal eusplenic individuals have less than 2% PkRBCs while asplenics have 15%–30%. Intermediate values are seen in hyposplenism. Thirty-three measurements of PkRBCs were made in 19 children with NS (mean age 7.5±0.8 years). PkRBCs were normal in all children tested (range 0–0.8%), including two patients with bacterial peritonitis associated with relapse. Thus we were unable to find evidence of hyposplenism in children with NS.     

Isolation of a Trypanosoma cruzi antigen by affinity chromatography with a monoclonal antibody. Preliminary evaluation of its possible applications in serological tests.

By affinity chromatography with a monoclonal antibody (163B6), obtained in our laboratory, we have isolated a T. cruzi antigen which could be useful for differential diagnosis of Chagas' disease from leishmaniasis. This antigen, a 52-kD protein, reacted with all sera from Chagas' disease patients tested but not with sera from patients with leishmania, in ELISA. The 52-kD antigen is widely distributed in the Trypanosoma genus since the 163B6 monoclonal antibody reacts with T. rangeli and 8 strains and a clone of T. cruzi epimastigotes.     

New anatomical reference systems for the bones of the foot and ankle complex: definitions and exploitation on clinical conditions

Medial tibial stress syndrome (MTSS) is one of the most common lower leg injuries in sporting populations. It accounts for between 6 and 16% of all running injuries, and up to 53% of lower leg injuries in military recruits. Various treatment modalities are available with varying degrees of success. In recalcitrant cases, surgery is often the only option. To evaluate whether ultrasound-guided injection of 15% dextrose for treatment of recalcitrant MTSS decreases pain and facilitates a return to desired activity levels for those who may otherwise be considering surgery or giving up the sport. The study design was a prospective consecutive case series involving eighteen patients: fifteen male and three female; (mean age = 31.2 years) with recalcitrant MTSS. They were referred from sports injury clinics across the UK, having failed all available conservative treatment. An ultrasound-guided sub-periosteal injection of 15% dextrose was administered by the same clinician (NP) along the length of the symptomatic area. Typically, 1 mL of solution was injected per cm of the symptomatic area. Pain was assessed using a 10-cm visual analog scale (VAS) at baseline, short-term, medium-term (mean 18 weeks), and long-term (mean 52 weeks) follow-up. Symptom resolution and return to activity were measured using a Likert scale at medium and long-term follow-up. Statistical analyses were performed using SPSS for Mac version 19.0.0 (IBM, New York, NY, US). The Shapiro-Wilk test was used to evaluate the normality of the distribution of data. Friedman’s non-parametric test was used to compare the within-patient treatment response over time. Post-hoc Wilcoxon signed-rank tests with Bonferroni corrections were performed to determine VAS average pain response to treatment over five paired periods. Patients reported a significant (p < 0.01) reduction in median VAS pain score at medium and long-term follow-up compared to baseline. Median improvement per patient was 4.5/10. Patients rated their condition as ‘much improved’ at medium-term follow-up and the median return to sports score was ‘returned to desired but not pre-injury level’ at medium-term and long-term follow-up. No adverse events were reported. Ultrasound-guided 15% dextrose prolotherapy injection has a significant medium-term effect on pain in MTSS. This benefit may be maintained long-term; however, more robust trials are required to validate these findings in the absence of controls. Clinicians should consider the use of ultrasound-guided injection of 15% dextrose as a viable treatment option to reduce pain and aid return to activity for patients with recalcitrant MTSS.     

Macular edema induced by phacoemulsification

Purpose: To characterise the association between lens phacoemulsification and the development of macular edema. Methods: We studied 15 patients who underwent lens phacoemulsification in our clinic between January and April 1998 performed by the same surgeon. Ultrasound power and cumulative time was noted. Follow-up was performed at 1 day, 1 week, 1, 3 and 6 months after operation. On each visit corneal thickness, best corrected visual acuity, biomicroscopy and fluorescein angiography were performed. Patients with systemic diseases and/or retinal diseases were not included. Results: Visual acuity was inversely related to the amount of energy delivered during phacoemulsification. In patients who had received more than 1 Joule of energy, fluorescein angiography revealed a higher incidence of blood retinal barrier breakdown. Corneal thickness was not correlated with the ultrasound energy used. Conclusions: Excessive use of power during phacoemulsification may hamper the postoperative evolution of cataract surgery. This revised version was published online in July 2006 with corrections to the Cover Date.     

Carbon monoxide inhibits apoptosis in vascular smooth muscle cells

OBJECTIVE: Carbon monoxide (CO) is generated from vascular smooth muscle cells via the degradation of heme by the enzyme heme oxygenase-1. Since smooth muscle cell apoptosis is associated with numerous vascular disorders, we investigated whether CO regulates apoptosis in vascular smooth muscle. METHODS AND RESULTS: Treatment of cultured rat aortic smooth muscle cells with a combination of cytokines (interleukin-1beta, 5 ng/ml; tumor necrosis factor-alpha, 20 ng/ml; interferon-gamma, 200 U/ml) for 48 h stimulated apoptosis, as demonstrated by DNA laddering, annexin V binding, and caspase-3 activation. However, the exogenous administration of CO inhibited cytokine-mediated apoptosis. The antiapoptotic action of CO was partially dependent on the activation of soluble guanylate cyclase and was associated with the inhibition of mitochondrial cytochrome c release and with the suppression of p53 expression. Incubation of smooth muscle cells with the cytokines also resulted in a pronounced increase in heme oxygenase-1 protein after 24 h of stimulation. The addition of the heme oxygenase inhibitor, zinc protoporphyrin-IX, or the CO scavenger, hemoglobin, stimulated apoptosis following 24 h of cytokine exposure. CONCLUSIONS: These results demonstrate that CO, either administered exogenously or endogenously derived from heme oxygenase-1 activity, inhibits vascular smooth muscle cell apoptosis. The ability of CO to block smooth muscle cell apoptosis may play an important role in blocking lesion formation at sites of vascular injury.     

Usefulness of the PARIS Score to Evaluate the Ischemic-hemorrhagic Net Benefit With Ticagrelor and Prasugrel After an Acute Coronary Syndrome

Introduction and objectives

The PARIS score allows combined stratification of ischemic and hemorrhagic risk in patients with ischemic heart disease treated with coronary stenting and dual antiplatelet therapy (DAPT). Its usefulness in patients with acute coronary syndrome (ACS) treated with ticagrelor or prasugrel is unknown. We investigated this issue in an international registry.

Baroreflex sensitivity in the elderly with silent myocardial ischemia

In order to assess high-pressure barocepture sensitivity and parasympathetic function in elderly patients with silent myocardial ischemia, we selected 45 inpatients in our geriatric unit for a prospective cohort study of patients with coronary heart disease. All patients were over 65 years of age (37 men and 8 women) and had coronary heart disease, documented by an angiographic study and electrocardiographic evidence of myocardial ischemia during exercise stress testing, performed according to the Bruce protocol. The subjects were divided in three subgroups: group 1 (22 patients) with electrocardiographic and echocardiographic history of myocardial infarction but no angina chest pain during exercise testing; group 2 (13 patients) with no exercise induced chest pain; and group 3 (10 patients) with exercise-induced chest pain. Baroceptor sensitivity was assessed in all subjects, by evaluating heart rate changes expressed in RR interval on the basis of changes in the mean arterial pressure during intravenous infusion of stepwise doses (50-100 and 150 mug) of phenylephrine hydrochloride. Heart rate changes were also evaluated during overshoot of the Valsalva maneuver (Valsalva max.), providing an index of parasympathetic activity. Our results showed that group two patients (only silent ischemia) had significantly (P>0.001) greater baroceptor sensitivity than the other two groups (group 2; 15.2+/-1.9 ms/mmHg; group 1: 10.0+/-1.7 ms/mmHg; and group 3: 9.8+/-1.7 ms/mmHg). Group two also showed a significant positive correlation (r=0.58; P<0.05) between baroceptor sensitivity and end-diastolic pressure and a significant inverse correlation (r=-0.672; P<0.05) between baroceptor sensitivity and the ejection fraction. Group 2 patients had a significantly longer RR interval than group 1 (P<0.05) and group 3 (P<0.05); a significant positive correlation (r=0.620; P<0.05) between Valsalva max. and end-diastolic pressure; and a significant inverse correlation (r=0.694; P<0.05) between Valsalva max. and the ejection fraction. Valsalva max. and baroceptor sensitivity correlated significantly in all three groups (group 1, r=0.707; P<0.001; group 2, r=0.94; P<0.001; and group 3; r=0.833; P<0.05). In conclusion our data suggest that elderly patients with silent ischemia appear to have an increased capacity for evoking parasympathetic reflexes that could inhibit pain perception.