Intracoronary brachytherapy after stenting de novo lesions in diabetic patients: results of a randomized intravascular ultrasound study

OBJECTIVES: We studied the efficacy of intracoronary brachytherapy (ICB) after successful coronary stenting in diabetic patients with de novo lesions. BACKGROUND: Intracoronary brachytherapy has proven effective in preventing recurrences in patients with in-stent restenosis. However, the role of ICB for the treatment of de novo coronary stenoses remains controversial. METHODS: Ninety-two patients were randomized to either ICB or no radiation after stenting. Primary end points were in-stent mean neointimal area (primary end point of efficacy) and minimal luminal area of the entire vessel segment (primary end point of effectiveness), as assessed by intravascular ultrasound at six-month follow-up. Quantitative coronary angiography analysis was performed at the target, injured, irradiated, and entire vessel segments. RESULTS: At follow-up, the in-stent mean neointimal area was 52% smaller in the ICB group (p < 0.0001). However, there was no difference in the minimal luminal area of the vessel segment (4.5 +/- 2.4 mm2 vs. 4.4 +/- 2.1 mm2). Restenosis rates increased progressively by the analyzed segment in the ICB group: target (7.1% vs. 20.9%, p = 0.07), injured (9.5% vs. 20.9%, p = NS), irradiated (14.3% vs. 20.9%, p = NS), and vessel segment (23.8% vs. 25.6%, p = NS). At one year, 1 cardiac death, 6 myocardial infarctions (MIs) (3 due to late stent thrombosis), and 10 target vessel revascularizations (TVRs) (6 due to the edge effect) occurred in the ICB group, whereas in the nonradiation group, there were 11 TVRs and no deaths or MIs. CONCLUSIONS: Intracoronary brachytherapy significantly inhibited in-stent neointimal hyperplasia after stenting in diabetic patients. However, clinically this was counteracted by the occurrence of the edge effect and late stent thrombosis.     

A collaborative study to establish the 1st International Standard for factor XIII plasma

BACKGROUND: An international collaborative study, involving 23 laboratories, was carried out, under the auspices of the FXIII Standardization Working Party (SWP), to calibrate the 1st International Standard (IS) for factor XIII (FXIII) plasma. METHODS: Potency estimates for the proposed candidate FXIII plasma (preparation Y: NIBSC code 02/206) were calculated relative to locally collected normal plasma pools (pool N), for both FXIII activity and antigen levels. RESULTS: Estimates of FXIII activity potency for preparation Y showed good agreement between laboratories, with an interlaboratory geometric coefficient of variation (GCV) of 11.5% and a mean value of 0.91 U mL(-1). Furthermore, there was a negligible difference in potencies by two commercially available methods, the potencies differing only by approximately 1%. Estimates of FXIII antigen (A(2)B(2) complex) potency for preparation Y showed good agreement between laboratories, with an interlaboratory GCV of 16.3% and a mean value of 0.93 U mL(-1). Accelerated degradation studies showed that the proposed standard is very stable, with a predicted loss of activity (and antigen) per year of< 0.06% at the recommended storage temperature of -20 degrees C. CONCLUSIONS: The suitability and potency of preparation Y were considered by the participants, members of the ISTH/SSC FXIII Subcommittee, the Scientific and Standardization Committee and the SWP. Following their approval, preparation Y was proposed to and accepted by the Expert Committee on Biological Standardization of the World Health Organization to be the 1st IS for FXIII plasma with an activity potency of 0.91 IU per ampoule and an antigen potency of 0.93 IU per ampoule.     

Biodistribution and tumor infectivity of semliki forest virus vectors in mice: effects of re-administration.

Semliki Forest virus (SFV)-based vectors have broad tropism, with the ability to infect cells from various origins, including those from tumors. These vectors express cytokines after intra-tumoral (IT) injection, and have therefore been used for inducing efficient anti-tumoral responses in several tumor models. We were interested in studying whether SFV vectors could escape from tumors after IT injection and whether they could target tumors if administered systemically. We analyzed the biodistribution of an SFV vector expressing luciferase (SFV-Luc) after intravenous (IV), intraperitoneal (IP), and IT administration in immunocompetent mice. SFV-Luc systemic inoculation led to high infectivity in heart and lung, and moderate levels of infectivity in spleen, kidney, and gonads, without gender being a factor in the outcome. Tumor-specific infection, without the vector spreading to other tissues, was achieved only by IT inoculation. We also investigated the effect of SFV pre-inoculation on subsequent vector administrations. Systemic inoculation with one dose of 10(7) vp (viral particles), or two doses of 10(6) vp of SFV-LacZ given with a 20-day interval between the doses, was able to strongly inhibit luciferase expression in animals re-inoculated systemically with SFV-Luc, correlating with high sera neutralizing antibodies titers. However, IT pre-inoculation with 10(8) vp of SFV-LacZ impaired tumor re-infection only moderately, thereby indicating that tumors can be treated with several doses of SFV vectors.     

Team-based approach reduces learning curve in robot-assisted laparoscopic radical prostatectomy

AIM: We assessed the team approach in reducing the learning curve during our 2-year experience transiting from open to robot-assisted laparoscopic radical prostatectomy (rLRP). METHODS: A team of three urologists progressed through assistant phase to console phase to obtain competency in robotic prostatectomy. One hundred patients underwent rLRP by this team using the da Vinci robotic surgical system from 1 February 2003 to 15 May 2005. RESULTS: The immediate perioperative outcome was divided into three corresponding time frames and the results demonstrated gradual improvement in outcome parameters. The mean set-up time and dissection time were 24+/-14 min and 182+/-52 min, respectively. The mean perioperative blood loss was 272+/-240 mL, and 7% of patients (n=7) required blood transfusion. The mean duration of bladder catheterization was 8.4+/-4.1 days, and mean hospital stay was 2.9+/-1.6 days. There was no perioperative mortality or conversion to open radical prostatectomy. Major complications (4%) included urethrovesical leak requiring re-operation, postoperative cerebrovascular accident, and transient ureteric obstruction. Minor complications (7%) included minor urethrovesical leak, bladder neck stenosis, and urinary tract infection. Mean follow up was 6.6+/-5.0 months. Pathological assessment showed pT2 disease in 55% and pT3 in 45% of specimens. CONCLUSIONS: A team-based approach to robot-assisted LRP helped to reduce the learning curve of the procedure for individual surgeons and continued to show significantly lower perioperative blood loss, transfusion requirements and postoperative pain compared to open radical retropubic prostatectomy.     

Use of a straight, side-hole delivery sheath for improved delivery of Amplatzer ASD occluder.

The Amplatzer ASD occluder may be difficult to position in some patients with a large atrial septal defect (ASD) or deficiency of one or more atrial septal rims. We developed a method to modify a Mullins transseptal sheath to enhance delivery. The resulting sheath is straight and has an exit orifice essential in the side of the distal portion of the sheath-a straight, side-hole (SSH) delivery sheath. We have used this modified delivery sheath in 140 successive patients with excellent results. The techniques of sheath modification and delivery of the device using the modified sheath are described.     

Microbiological changes in subgingival flora after treatment with amoxicillin-clavulanic acid

The association amoxicillin-clavulanic acid can be employed as an alternative to the usual antibiotic therapy of periodontitis. The purpose of this study was to determine subgingival microbial changes in 33 patients with periodontitis after using amoxicillin (500 mgrs.-t.i.d.) and clavulanic acid (125 mgrs.-t.i.d.) for 5 days. It resulted clinically in a decrease of both gingival index and plaque index (not significant) and microbiologically in absence of the main bacterial pathogens found pretreatment, such as Bacteroides melaninogenicus, Bacteroides intermedius, Eikenella corrodens and Actinomyces sp., although it was not able to eliminate Actinobacillus asinomycetemcomitans from a juvenile periodontitis and from a prepuberal periodontitis patient. Atibiotic susceptibility testing showed that all bacteria tested were sensitive to this antibiotic. Although this short term study shows good microbial response of main periodontal pathogens, long term studies are necessary to assess the effect of this antibiotic in periodontitis therapy.     

Aortic stenosis with left ventricular systolic dysfunction: a severe disease but with good surgical prognosis

From our series of 72 patients with severe valvular aortic stenosis, we identified 19 showing features of left ventricular systolic disfunction (ventriculographic ejection fraction less than 55% and/or fractional shortening less than 30% at M-mode echocardiography). In these patients, we found a significant inverse correlation between the fractional shortening and the systolic wall stress (r = 0.79, p less than 0.001). Clinically, 18 of the 19 patients were in NYHA class III (n = 11) or IV (n = 5), and two died before they could be operated upon. The remaining 17 had their aortic valve replaced (coronary artery bypass surgery was simultaneously performed in 2 patients). After a mean follow-up of 18 months, all patients are alive and show substantial symptomatic improvement (15 patients in class I and 2 patients in class II). Cardiothoracic index was reduced (61 +/- 5% preoperatively versus 52 +/- 5% postoperatively), and fractional shortening changed from 21 +/- 5% to 30 +/- 5%. The latter remains under normal limits in two thirds of the patients. Our results lend support to the idea that the systolic left ventricular dysfunction in aortic stenosis is due to the increased afterload, rather than to an intrinsic contractility defect. This explains the great functional improvement after the reduction of the systolic wall stress achieved by surgery.     

Congenital intracranial filariasis: A case report

We present the case of a newborn with intracranial extra-axial collections which mere partially calcified. The underlying cause was shown to be filariasis which had been transmitted from the mother.     

Mapping the platelet profile for functional genomic studies and demonstration of the effect size of the GP6 locus

BACKGROUND: Evidence suggests the wide variation in platelet response within the population is genetically controlled. Unraveling the complex relationship between sequence variation and platelet phenotype requires accurate and reproducible measurement of platelet response. OBJECTIVE: To develop a methodology suitable for measuring signaling pathway-specific platelet phenotype, to use this to measure platelet response in a large cohort, and to demonstrate the effect size of sequence variation in a relevant model gene. METHODS: Three established platelet assays were evaluated: mobilization of [Ca(2+)](i), aggregometry and flow cytometry, each in response to adenosine 5'-diphosphate (ADP) or the glycoprotein (GP) VI-specific crosslinked collagen-related peptide (CRP). Flow cytometric measurement of fibrinogen binding and P-selectin expression in response to a single, intermediate dose of each agonist gave the best combination of reproducibility and inter-individual variability and was used to measure the platelet response in 506 healthy volunteers. Pathway specificity was ensured by blocking the main subsidiary signaling pathways. RESULTS: Individuals were identified who were hypo- or hyper-responders for both pathways, or who had differential responses to the two agonists, or between outcomes. 89 individuals, retested three months later using the same methodology, showed high concordance between the two visits in all four assays (r(2) = 0.872, 0.868, 0.766 and 0.549); all subjects retaining their phenotype at recall. The effect of sequence variation at the GP6 locus accounted for approximately 35% of the variation in the CRP-XL response. CONCLUSION: Genotyping-phenotype association studies in a well-characterized, large cohort provides a powerful strategy to measure the effect of sequence variation in genes regulating the platelet response.     

Benign symmetric lipomatosis of the tongue in Madelung''s disease

INTRODUCTION: Madelung's disease is characterized by benign, non-encapsulated accumulations of fat in a symmetrical manner. Although rare, symmetrical lipomatosis involving the tongue exclusively has been previously reported. Here another case is presented of Madelung's disease involving the tongue. CASE REPORT: A 57-year-old woman was referred with the diagnosis of Madelung's disease, with slight difficulty in swallowing, dysarthria and dyspnoea while sleeping due to tongue swelling. Clinical examination revealed multiple, large disfiguring soft masses involving neck, upper arms and hips. There was enlargement of the tongue with bilateral protrusions and buccal displacement of the teeth. The masses were soft and non-tender. Bilateral partial glossectomy was performed under general anaesthesia. Histology revealed adipose tissue, interspersed within the lingual musculature. DISCUSSION: Lipomas in Madelung's disease are characterized by multiplicity, non-encapsulation and invasiveness. Over the years, the fat deposits enlarge significantly, become cosmetically deforming, and cause dyspnoea and dysphagia in advanced cases. The aetiology of benign symmetrical lipomatosis is still unknown. It is often accompanied by liver dysfunction probably due to alcoholism. Treatment is limited to surgical removal of the fatty tissue, in patients with a severe cosmetic deformity causing psychological stress, and in patients with dyspnoea or dysphagia if there is restriction of the aerodigestive tract.