Prostate-Specific Antigen (PSA)-Based Population Screening for Prostate Cancer: An Evidence-Based Analysis.

BACKGROUND: Prostate cancer (PC) is the most commonly diagnosed non-cutaneous cancer in men and their second or third leading cause of cancer death. Prostate-specific antigen (PSA) testing for PC has been in common practice for more than 20 years. OBJECTIVES: A systematic review of the scientific literature was conducted to determine the effectiveness of PSA-based population screening programs for PC to inform policy decisions in a publicly funded health care system. DATA SOURCES: A systematic review of bibliographic databases was performed for systematic reviews or randomized controlled trials (RCT) of PSA-based population screening programs for PC. REVIEW METHODS: A broad search strategy was employed to identify studies reporting on key outcomes of PC mortality and all-cause mortality. RESULTS: The search identified 5 systematic reviews and 6 RCTs. None of the systematic reviews found a statistically significant reduction in relative risk (RR) of PC mortality or overall mortality with PSA-based screening. PC mortality reductions were found to vary by country, by screening program, and by age of men at study entry. The European Randomized Study of Screening for Prostate Cancer found a statistically significant reduction in RR in PC mortality at 11-year follow-up (0.79; 95% CI, 0.67-0.92), although the absolute risk reduction was small (1.0/10,000 person-years). However, the primary treatment for PCs differed significantly between countries and between trial arms. The American Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) found a statistically non-significant increase in RR for PC mortality with 13-year follow-up (1.09; 95% CI, 0.87-1.36). The degree of opportunistic screening in the control arm of the PLCO trial, however, was high. None of the RCTs found a reduction in all-cause mortality and all found a statistically significant increase in the detection of mainly low-risk, organ-confined PCs in the screening arm. CONCLUSIONS: There was no evidence of a PC mortality reduction in the American PLCO trial, which investigated a screening program in a setting where opportunistic screening was already common practice. Given that opportunistic PSA screening practices in Canada are similar, it is unlikely that the introduction of a formal PSA screening program would reduce PC mortality.

Magnetic Resonance-Guided High-Intensity Focused Ultrasound (MRgHIFU) Treatment of Symptomatic Uterine Fibroids: An Evidence-Based Analysis.

BACKGROUND: Magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) is a noninvasive uterine-preserving treatment alternative to hysterectomy for women with symptomatic uterine leiomyomas (fibroids). Uterine fibroids commonly occur, have a broad impact on women's health and lifestyle, continue to be the main indication for hysterectomy, and represent a costly public health burden. OBJECTIVES: The objectives of the analysis were to evaluate patients' eligibility for MRgHIFU treatment of symptomatic uterine fibroids and the technical success, safety, effectiveness, and durability of this treatment. The review also compared the safety and effectiveness of MRgHIFU with other minimally invasive uterine-preserving treatments and surgeries for uterine fibroids. METHODS: A literature search was performed on March 27, 2014, using Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid EMBASE, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), and EBM Reviews, for studies published from January 1, 2000, to March 27, 2014. RESULTS: The evidence review identified 2 systematic reviews, 2 RCTs, 45 cohort study reports, and 19 case reports involving HIFU treatment of symptomatic uterine fibroids. Eligibility for MRgHIFU treatment was variable, ranging from 14% to 74%. In clinical cohort studies involving 1,594 patients, 26 major complications (1.6%) were reported. MRgHIFU resulted in statistically and clinically significant reductions in fibroid-related symptoms in studies conducted in 10 countries, although few involved follow-up longer than 1 year. Retreatment rates following MRgHIFU were higher in early clinical studies involving regulated restrictions in the extent of fibroid ablation than in later reports involving near-complete ablation. Emergent interventions, however, were rare. Although a desire for fertility was an exclusion criteria for treatment, spontaneous term pregnancies did occur following HIFU. There were no randomized trials comparing MRgHIFU and other guidance methods, other minimally invasive treatments, or surgeries for symptomatic uterine fibroids. Limitations with MRgHIFU included restricted eligibility, requirement for a dedicated MR device to guide the treatment, lengthy procedure time, and loss of MR opportunity time. CONCLUSIONS: For women failing medical therapy and seeking alternatives to hysterectomy for symptomatic uterine fibroids, MRgHIFU provides a safe and effective, noninvasive, uterine-preserving treatment from which they rapidly recover. The treatment advantages of MRgHIFU are potentially offset by restrictive eligibility, lengthy procedure time, and dependence on availability of an MR device. The lack of comparative evidence between MRgHIFU and other, more established uterine-preserving treatments limits informed decision making among treatment options.

Optical Coherence Tomography Monitoring Strategies for A-VEGF-Treated Age-Related Macular Degeneration: An Evidence-Based Analysis.

BACKGROUND: New anti-angiogenesis pharmacotherapies have dramatically altered treatment of age-related macular degeneration (AMD), the leading cause of blindness in older adults. Monthly intraocular injections however, are extremely burdensome to ophthalmologists, patients, and their families. Repeated injections also increase risks of complications or adverse events. Although the pharmacokinetics of anti-vascular endothelial growth factor (A-VEGF) drugs are fairly well known, an individuals' AMD presentation and their pharmacodynamics or response to the drug has been shown to be extremely variable. Therefore treating everyone on the same fixed or standard regimen has potential for undertreating or overtreating patients, and drug costs are not trivial. OBJECTIVES: To review monitoring strategies and to evaluate the role of optical coherence tomography (OCT) in guiding management of A-VEGF-treated neovascular AMD (n-AMD) patients. DATA SOURCES: Systematic reviews of biographic databases for studies published between 2008 and February 2013 involving A-VEGF-treated n-AMD patients monitored in longitudinal follow-up. REVIEW METHODS: Studies were grouped according to varying treatments, monitoring schedules, and re-treatment protocols reported for n-AMD patients treated with A-VEGF. Several outcomes were evaluated across strategies including visual acuity (VA), retinal anatomy, re-treatment criteria and frequencies of clinical follow-up, OCT imaging investigations, and intravitreal injections. Results were summarized qualitatively, as heterogeneity in study objectives and methods precluded formal meta-analysis. RESULTS: A systematic review identified 18 randomized controlled trials (RCTs) and 20 observational studies involving A-VEGF treatment employing various monitoring and as-needed (PRN) re-treatment protocols. Several maintenance strategies were unsuccessful, resulting in lower VA gains and stabilization than monthly injections in A-VEGF-treated n-AMD. These included fixed quarterly treatment; fixed quarterly monitoring and PRN re-treatment; and monthly monitoring with either VA-guided re-treatment or quantitative-only VA/OCT- (central retinal thickness [CRT] > 100 µm) guided re-treatment. PRN re-treatment strategies with A-VEGF on the basis of monthly follow-up and rigorous reviews of OCT qualitative and quantitative measures of disease activity did decrease injection burden while maintaining visual gains. Gains in VA obtained with PRN re-treatment in usual clinical practice, however, were not as high as gains in clinical trials. CONCLUSIONS: To reduce treatment burden and provide a more individualized treatment strategy for n-AMD patients, OCT/VA-guided PRN treatment strategies have become the preferred and the dominant maintenance strategy. Success of these strategies, however, is dependent on close monitoring and adherence to tightly defined re-treatment criteria.

Collagen cross-linking using riboflavin and ultraviolet-a for corneal thinning disorders: an evidence-based analysis.

OBJECTIVE: The main objectives for this evidence-based analysis were to determine the safety and effectiveness of photochemical corneal collagen cross-linking with riboflavin (vitamin B(2)) and ultraviolet-A radiation, referred to as CXL, for the management of corneal thinning disease conditions. The comparative safety and effectiveness of corneal cross-linking with other minimally invasive treatments such as intrastromal corneal rings was also reviewed. The Medical Advisory Secretariat (MAS) evidence-based analysis was performed to support public financing decisions. SUBJECT OF THE EVIDENCE-BASED ANALYSIS: The primary treatment objective for corneal cross-linking is to increase the strength of the corneal stroma, thereby stabilizing the underlying disease process. At the present time, it is the only procedure that treats the underlying disease condition. The proposed advantages for corneal cross-linking are that the procedure is minimally invasive, safe and effective, and it can potentially delay or defer the need for a corneal transplant. In addition, corneal cross-linking does not adversely affect subsequent surgical approaches, if they are necessary, or interfere with corneal transplants. The evidence for these claims for corneal cross-linking in the management of corneal thinning disorders such as keratoconus will be the focus of this review. The specific research questions for the evidence review were as follows: TECHNICAL: How technically demanding is corneal cross-linking and what are the operative risks? SAFETY: What is known about the broader safety profile of corneal cross-linking?Effectiveness - Corneal Surface Topographic Affects:What are the corneal surface remodeling effects of corneal cross-linking?Do these changes interfere with subsequent interventions, particularly corneal transplant known as penetrating keratoplasty (PKP)?Effectiveness -Visual Acuity:What impacts does the remodeling have on visual acuity?Are these impacts predictable, stable, adjustable and durable?Effectiveness - Refractive Outcomes: What impact does remodeling have on refractive outcomes?Effectiveness - Visual Quality (Symptoms): What impact does corneal cross-linking have on vision quality such as contrast vision, and decreased visual symptoms (halos, fluctuating vision)?Effectiveness - Contact lens tolerance: To what extent does contact lens intolerance improve after corneal cross-linking?Vision-Related QOL: What is the impact of corneal cross-linking on functional visual rehabilitation and quality of life?PATIENT SATISFACTION: Are patients satisfied with their vision following the procedure?Disease Process:What impact does corneal cross-linking have on the underling corneal thinning disease process?Does corneal cross-linking delay or defer the need for a corneal transplant?What is the comparative safety and effectiveness of corneal cross-linking compared with other minimally invasive treatments for corneal ectasia such as intrastromal corneal rings? CLINICAL NEED: TARGET POPULATION AND CONDITION Corneal ectasia (thinning) disorders represent a range of disorders involving either primary disease conditions, such as keratoconus (KC) and pellucid marginal corneal degeneration, or secondary iatrogenic conditions, such as corneal thinning occurring after laser in situ keratomileusis (LASIK) refractive surgery. Corneal thinning is a disease that occurs when the normally round dome-shaped cornea progressively thins causing a cone-like bulge or forward protrusion in response to the normal pressure of the eye. The thinning occurs primarily in the stroma layers and is believed to be a breakdown in the collagen process. This bulging can lead to irregular astigmatism or shape of the cornea. Because the anterior part of the cornea is responsible for most of the focusing of the light on the retina, this can then result in loss of visual acuity. The reduced visual acuity can make even simple daily tasks, such as driving, watching television or reading, difficult to perform. Keratoconus is the most common form of corneal thinning disorder and involves a noninflammatory chronic disease process of progressive corneal thinning. Although the specific cause for the biomechanical alterations in the corneal stroma is unknown, there is a growing body of evidence suggesting that genetic factors may play an important role. Keratoconus is a rare disease (< 0.05% of the population) and is unique among chronic eye diseases because it has an early onset, with a median age of 25 years. Disease management for this condition follows a step-wise approach depending on disease severity. Contact lenses are the primary treatment of choice when there is irregular astigmatism associated with the disease. Patients are referred for corneal transplants as a last option when they can no longer tolerate contact lenses or when lenses no longer provide adequate vision. Keratoconus is one of the leading indications for corneal transplants and has been so for the last 3 decades. Despite the high success rate of corneal transplants (up to 20 years) there are reasons to defer it as long as possible. Patients with keratoconus are generally young and a longer-term graft survival of at least 30 or 40 years may be necessary. The surgery itself involves lengthy time off work and postsurgery, while potential complications include long-term steroid use, secondary cataracts, and glaucoma. After a corneal transplant, keratoconus may recur resulting in a need for subsequent interventions. Residual refractive errors and astigmatism can remain challenges after transplantation, and high refractive surgery and regraft rates in KC patients have been reported. Visual rehabilitation or recovery of visual acuity after transplant may be slow and/or unsatisfactory to patients. DESCRIPTION OF TECHNOLOGY/THERAPY: Corneal cross-linking involves the use of riboflavin (vitamin B(2)) and ultraviolet-A (UVA) radiation. A UVA irradiation device known as the CXL® device (license number 77989) by ACCUTECH Medical Technologies Inc. has been licensed by Health Canada as a Class II device since September 19, 2008. An illumination device that emits homogeneous UVA, in combination with any generic form of riboflavin, is licensed by Health Canada for the indication to slow or stop the progression of corneal thinning caused by progressive keratectasia, iatrogenic keratectasia after laser-assisted in situ keratomileusis (LASIK) and pellucid marginal degeneration. The same device is named the UV-X® device by IROCMedical, with approvals in Argentina, the European Union and Australia. UVA devices all use light emitting diodes to generate UVA at a wavelength of 360-380 microns but vary in the number of diodes (5 to 25), focusing systems, working distance, beam diameter, beam uniformity and extent to which the operator can vary the parameters. In Ontario, CXL is currently offered at over 15 private eye clinics by refractive surgeons and ophthalmologists. The treatment is an outpatient procedure generally performed with topical anesthesia. The treatment consists of several well defined procedures. The epithelial cell layer is first removed, often using a blunt spatula in a 9.0 mm diameter under sterile conditions. This step is followed by the application of topical 0.1% riboflavin (vitamin B(2)) solution every 3 to 5 minutes for 25 minutes to ensure that the corneal stroma is fully penetrated. A solid-state UVA light source with a wavelength of 370 nm (maximum absorption of riboflavin) and an irradiance of 3 mW/cm(2) is used to irradiate the central cornea. Following treatment, a soft bandage lens is applied and prescriptions are given for oral pain medications, preservative-free tears, anti-inflammatory drops (preferably not nonsteroidal anti-inflammatory drugs, or NSAIDs) and antibiotic eye drops. Patients are recalled 1 week following the procedure to evaluate re-epithelialization and they are followed-up subsequently. EVIDENCE-BASED ANALYSIS METHODS: A literature search was conducted on photochemical corneal collagen cross-linking with riboflavin (vitamin B(2)) and ultraviolet-A for the management of corneal thinning disorders using a search strategy with appropriate keywords and subject headings for CXL for literature published up until April 17, 2011. The literature search for this Health Technology Assessment (HTA) review was performed using the Cochrane Library, the Emergency Care Research Institute (ECRI) and the Centre for Reviews and Dissemination. The websites of several other health technology agencies were also reviewed, including the Canadian Agency for Drugs and Technologies in Health (CADTH) and the United Kingdom's National Institute for Clinical Excellence (NICE). The databases searched included OVID MEDLINE, MEDLINE IN-Process and other Non-Indexed Citations such as EMBASE. As the evidence review included an intervention for a rare condition, case series and case reports, particularly for complications and adverse events, were reviewed. A total of 316 citations were identified and all abstracts were reviewed by a single reviewer for eligibility. For those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. (ABSTRACT TRUNCATED)

Therapeutic failure of uterine fibroid embolization caused by underlying leiomyosarcoma.

The authors describe an unusual case in which continued growth of uterine fibroids in a postmenopausal patient after polyvinyl alcohol embolization therapy prompted hysterectomy, which revealed an underlying leiomyosarcoma. The surgery was nearly fatal as a result of venous bleeding, and parasitization of blood from adjacent bowel by the tumor was noted. The difficulty of preoperative diagnosis of leiomyosarcoma and the need for diligent follow-up after uterine fibroid embolization are discussed.

Screening for oropharyngeal dysphagia in stroke: insufficient evidence for guidelines.

There is no evaluation of the evidence for the screening of oropharyngeal dysphagia in stroke. We reviewed the literature on clinical screening for oropharyngeal dysphagia in adults with stroke to determine (a) the accuracy of different screening tests used to detect dysphagia defined by abnormal oropharyngeal physiology on videofluoroscopy and (b) the health outcomes reported and whether screening alters those outcomes. Peer-reviewed English-language and human studies were sought through Medline (from 1966 to July 1997) by using the key words cerebrovascular disorders and deglutition disorders, relevant Internet addresses, and extensive hand searching of bibliographies of identified articles. Of the 154 sources identified, 89 articles were original, peer-reviewed, and focused on oropharyngeal dysphagia in stroke patients. To evaluate the evidence, the next selection identified 10 articles on the comparison of screening and videofluoroscopic findings and three articles on screening and health outcomes. Evidence was rated according to the level of study design by using the values of the Canadian Task Force on Periodic Health Examination. From the identified screening tests, most of the screenings were related to laryngeal signs (63%) and most of the outcomes were related to physiology (74%). Evidence for screening accuracy was limited because of poor study design and the predominant use of aspiration as the diagnostic reference. Only two screening tests were identified as accurate: failure on the 50-ml water test (likelihood ratio = 5.7, 95% confidence interval = 2.5-12.9) and impaired pharyngeal sensation (likelihood ratio = 2.5, 95% confidence interval = 1.7-3.7). Limited evidence for screening benefit suggested a reduction in pneumonia, length of hospital stay, personnel costs, and patient charges. In conclusion, screening accuracy needs to be assessed by using both abnormal physiology and aspiration as diagnostic markers for dysphagia. Large well-designed trials are needed for more conclusive evidence of screening benefit.

Recurrent Crohn's disease in the duodenum and jejunum following extensive small bowel resection and jejunocolonic anastamosis: radiologic findings in twenty-five patients.

BACKGROUND: To evaluate the radiologic features of recurrent Crohn's disease after extensive enteric resection and jejunocolostomy. METHODS: We reviewed the small bowel studies of 25 patients with recurrent enteritis and less than 125 cm of jejunum following enteric resection and jejunocolostomy and the studies of 27 patients with jejunitis in an intact jejunum. RESULTS: Twenty-three patients with recurrences had neoterminal jejunitis, six under 10 cm, 10 over 10 cm and continuous, and seven with skip lesions (six jejunal, one duodenal). Two had isolated jejunitis or duodenitis. Three with continuous disease had lengthy recurrences. Enteritis showed only one or two abnormalities in 12 of 25 patients with recurrences and in two of 27 with disease in the intact jejunum. Recurrent jejunitis and jejunitis in the intact jejunum showed similar frequencies of mucosal thickening, strictures, ulceration and its complications, skip lesions, sacculation, obstructive dilatation, featureless mucosa, and polyps, and significantly different frequencies only of mesenteric masses. Recurrent jejunitis and terminal ileitis showed significantly different frequencies of mucosal thickening, strictures, ulceration and its complications, skip lesions, sacculation, obstructive dilatation, and mesenteric masses, and similar frequencies only of a featureless mucosa. CONCLUSIONS: The neoterminal jejunum is the most common site of recurrence and the only site in almost 25%. Jejunitis remote from the fecal stream is also frequent, but duodenitis is not. Recurrences are seldom extensive and often show only one or two radiographic findings. The frequencies of most lesions in recurrent jejunitis do not differ significantly from those in jejunitis in the intact jejunum but do differ from those in terminal ileitis.

Interventional radiology and the use of metal stents in nonvascular clinical practice: a systematic overview.

PURPOSE: The intent of this systematic overview was to describe the clinical role of metal stents in nonvascular health care interventions and the level of evidence supporting their use. MATERIALS AND METHODS: Structured searches of Medline were conducted and limited to original peer-reviewed articles published in English. RESULTS: Clinical practice involving metal stents was reported in more than 109 clinical series involving 4,753 patients. Stents were placed mainly for palliation of malignant biliary, esophageal, and airway obstruction in patients who were untreatable or had surgically unresectable lesions. Assessment of these interventions has so far centered on safety and technical success. Efficacy, quality of life, and costing factors were not routinely reported. Randomized trial evidence was available but limited; six randomized trials involving metal stents have been reported. Three trials involved biliary malignant obstruction, and all three reported metal stent (132 patients) palliation to be superior to plastic stent palliation (136 patients) based on longer patency and lower reintervention costs. Safety and complication differences between stents, however, were inconsistent across trials. In three trials involving esophageal malignant obstruction, metal stent (82 patients) palliation was reported to be superior to plastic stent (41 patients), based on lower complication and reintervention rates, and superior to laser therapy (18 patients), based on better dysphagia relief. CONCLUSION: Use of metal stents has been reported for obstructed ducts and passageways of most body systems. There is, however, limited controlled trial evidence confirming the advantages of their use over plastic stents or other forms of treatment.

Internalisation of the bleomycin molecules responsible for bleomycin toxicity: a receptor-mediated endocytosis mechanism.

Bleomycin (BLM) does not diffuse through the plasma membrane but nevertheless displays cytotoxic activity due to DNA break generation. The aim of the study was to describe the mechanism of BLM internalisation. We previously provided evidence for the existence of BLM-binding sites at the surface of DC-3F Chinese hamster fibroblasts, as well as of their involvement in BLM cytotoxicity on DC-3F cells and related BLM-resistant sublines. Here we report that A253 human cells and their BLM-resistant subline C-10E also possessed a membrane protein of ca. 250 kDa specifically binding BLM. Part of this C-10E cell resistance could be explained by a decrease in the number of BLM-binding sites exposed at the cell surface with respect to A253 cells. The comparison between A253 and DC-3F cells exposing a similar number of BLM-binding sites revealed that the faster the fluid phase endocytosis, the greater the cell sensitivity to BLM. Moreover, the experimental modification of endocytotic vesicle size showed that BLM cytotoxicity was directly correlated with the flux of plasma membrane area engulfed during endocytosis rather than with the fluid phase volume incorporated. Thus, BLM would be internalised by a receptor-mediated endocytosis mechanism which would first require BLM binding to its membrane receptor and then the transfer of the complex into intracellular endocytotic vesicles, followed by BLM entry into the cytosol, probably from a nonacidic compartment.

Fluoroscopically-guided manipulation of malfunctioning peritoneal dialysis catheters.

OBJECTIVE: To review our experience with fluoroscopic evaluation and manipulation of malpositioned, malfunctioning, peritoneal dialysis (PD) catheters. MATERIALS AND METHODS: Thirty-one patients, over a 5-year period (1 May 1992 to 30 April 1997) with malfunctioning PD catheters, who had fluoroscopically-guided manipulation were reviewed. Catheters were manipulated using a malleable aluminum bar and, if necessary, guide wires or other stiffeners. Technical success was assessed on the basis of adequate, fluoroscopically verified, catheter placement at the time of the procedure and improved flows. A functional PD catheter at 30 days post manipulation was considered to be a clinically successful manipulation. RESULTS: There were 41 manipulations [33 initial (IM) and 8 remanipulations (RM)] for malpositioned or kinked catheters. In 31 (19 male, 12 female) patients ranging in age from 31 to 76 years (mean age 60 years), the initial technical success rate was 85% for IM (n = 28/33) and 63% (n = 5/8) for RM. The overall clinical success rate, or 30-day primary patency, was 55% for IM (n = 18/33) and 63% for RM. Catheter function (combined IM and RM) continued for a median 869 days (95% CI: 118, 1620). No early complications were noted. CONCLUSIONS: Fluoroscopic manipulation, including attempts at remanipulation, of PD catheters is a safe procedure. The technique is a simple, inexpensive, and effective way of prolonging PD catheter life, thereby reducing the number of surgical interventions.

Improved retroperitoneal and gastrointestinal sonography using oral contrast agents in a porcine model.

OBJECTIVE: Abdominal sonography can be compromised by the presence of air within the scanning field. Gas-displacing oral contrast agents have the potential to improve the diagnostic yield of routine abdominal sonography. The purpose of this study was to investigate two oral contrast agents and water and to compare their ability to improve abdominal sonography with an unenhanced baseline study and each other in a porcine model. MATERIALS AND METHODS: The acoustic properties of agent 1 (Oralex; Molecular Biosystems, San Diego, CA), a suspension of polydextrose in purified water; agent 2, a homemade agent (named BMW), a suspension of polysaccharide particles in water; and water were assessed in finger phantoms under laboratory conditions. Each solution was subsequently evaluated in 10 pigs, for a total of 30 animals. The bolus character, gas artifact, abdominal viscera, vessels, and gut wall were graded from 1 (nondiagnostic) to 5 (excellent) in the unenhanced and postcontrast states. Postcontrast grades were compared with unenhanced baseline grades using the Wilcoxon signed-rank correlation. Agents were compared with each other using the Mann-Whitney U test (Wilcoxon rank sum test). RESULTS: All three solutions were hypoechoic, were homogeneous, and showed minimal attenuation and backscatter. Both oral contrast agents had excellent bolus characteristics (agent 1, grade 5.0 +/- 0; agent 2, grade 4.6 +/- 0.5), displaced gas from the scanning field, and significantly improved visibility in all categories, particularly the gut. No difference in performance was found between agents 1 and agent 2. Water had poor bolus characteristics (grade 1.3 +/- 0.48) and did not improve visibility over baseline. CONCLUSION: The acoustic in vitro properties of agent 1 and agent 2 approach that of an ideal sonographic contrast agent. Both agents are superior to water in their improvement of direct visualization of the retroperitoneum and the gut in abdominal sonography in a porcine model.

Image-guided insertion of the Uldall tunneled hemodialysis catheter: technical success and clinical follow-up.

PURPOSE: To evaluate the technical success, complication rates, and survival time of the Uldall double-lumen catheter placed by interventional radiologists in patients presenting to a hemodialysis clinic. MATERIALS AND METHODS: Patients eligible for this study included those with end-stage renal disease (ESRD) who had failed peripheral vascular access or who were awaiting access at a hemodialysis unit between June 1993 and March 1996. All catheters were placed under fluoroscopic and ultrasound guidance in the angiography suite. RESULTS: Attempts were made to insert 130 catheters into jugular veins in a consecutive series of 61 patients with ESRD. The accumulated catheter experience in this cohort was 15,380 days and the median survival time was 141 days (95% confidence interval [CI]; 116 days-166 days). One hundred twenty-one catheters (93%) were successfully inserted, mainly (94%) into the internal jugular vein. Excellent dialysis blood flow rate was obtained-on average 365 mL/min (95% CI; 350-379 mL/min). The overall infection rate, including exit site (n = 13), sepsis (n = 19), and clavicular osteomyelitis (n = 1), was 2.1 episodes per 1,000 catheter days. CONCLUSIONS: This catheter is recommended for acute and longer term hemodialysis for patients without peripheral vascular access. It can be inserted percutaneously, the same internal jugular vein can be used repeatedly with few complications and good blood flow, and the technique can be easily learned by any experienced angiographer.

Case for active physician involvement in US practice.

PURPOSE: To assess the benefit of active physician involvement in ultrasound (US) examinations. MATERIALS AND METHODS: Concordance of findings by technologists and physicians was assessed prospectively for examinations of 1,510 consecutive patients who underwent US during regular working hours. RESULTS: Overall concordance was generally good (74%). However, in cases in which a major or minor new diagnosis was made from the US scan, concordance rates were substantially lower (36% and 32%, respectively). Agreement varied with the type of examination. The discordance rate for obstetric examinations (17%) was only half that for abdominal and pelvic examinations (31%). Concordance improved with increasing years of experience of the technologist. CONCLUSION: An active role of physicians in the overall conduct of US examinations is essential to optimize provision of a complete, accurate report.

Monobloc and facial bipartition osteotomies: quantitative assessment of presenting deformity and surgical results based on computed tomography scans.

PURPOSE: The results of monobloc (MB) or facial bipartition (FB) osteotomies on 23 consecutive patients operated on between 1987 and 1991 were evaluated. PATIENTS AND METHODS: A previously described method of clinically relevant linear measurements taken from preoperative and postoperative computed tomographic scans of these patients was used to document their presenting dysmorphology and the results of surgical correction initially and 1 year after operation. These data were compared with control values, and a percentage of normal for each measurement was derived for each patient. RESULTS: In the patients with craniofacial dysostosis undergoing an MB osteotomy, the initial cranial vault length (87% of normal), medial orbital wall length (87%), zygomatic arch length (84%), and extent of globe protrusion (134%) all indicated horizontal (anterior-posterior) deficiency of the upper and middle face. After surgery, these measurements moved closer to age-matched control values. At the 1-year interval a minor degree of relapse was evident. In the patients with craniofacial dysostosis who were believed to need an FB osteotomy, the globe protrusion (142% of normal), medial orbital wall length (85%), and zygomatic arch lengths (83%) all indicated horizontal (anterior-posterior) deficiency in the upper and middle face. In addition, the anterior interorbital distance (123% of normal), mid-interorbital distance (122%), and intertemporal distance (126%) all indicated upper face hypertelorism. As a result of the FB osteotomy, anterior bony projection was achieved, and the hypertelorism was improved, but fell short of age-matched normal values. In the patients with frontonasal dysplasia, cranio-orbital clefting, and isolated orbital hypertelorism who underwent an FB osteotomy, preoperative measurements showed a distinct widening of the whole upper midface with forward projection of the medial relative to the lateral orbital walls. The orbital measurements revealed a substantially widened anterior interorbital distance (175% of normal), increased mid-interorbital distance (123%), and an increased distance between the lateral orbital walls (106%). After the surgical procedure, these measurements were improved and relatively stable but not completely normalized. CONCLUSION: The use of quantitative measurements in the initial evaluation, intraoperative skeletal reshaping, and assessment of early and late reconstructive results provides useful benchmarks.

Facial sensibility in adolescents with and without clefts 1 year after undergoing Le Fort I osteotomy.

Static two-point discrimination, pressure, and vibratory threshold values were measured at standard coordinates in the area corresponding to the infraorbital nerve distribution in 59 adolescents 1 year after undergoing LeFort I osteotomy. The patients were divided into three groups: those born with unilateral cleft lip and palate (n = 30; mean age, 18 years; SD = 2); those with bilateral cleft lip and palate (n = 12; mean age, 19 years; SD = 3); and those without a cleft (n = 17; mean age, 19 years; SD = 3). One year after the osteotomy, none of the patients complained of altered sensibility in the maxillary vestibular mucosa, gingiva, or upper lip and cheek regions. No significant differences were found between the mean postoperative sensibility values of patients with and without clefts, indicating that the presence of clefting did not affect sensory recovery. Mean postoperative static two-point discrimination values were higher than preoperative values in all areas tested and in all patient groups. These results suggest that the sensory recovery, although incomplete, was strong enough to mask any subjective feelings of changes in sensory function.

Involvement of membrane bleomycin-binding sites in bleomycin cytotoxicity.

The authors have recently shown the existence of bleomycin (BLM)-binding sites at the surface of DC-3F cells. In order to study the involvement of these sites in the sensitivity of the cells to bleomycin several BLM-resistant cell lines from DC-3F cells were analysed. These mutants were obtained by electrotransfection of the Sh ble gene (D/BlmI cells) or the Sh ble-beta Gal fusion gene (D/BlmII cells) and/or by continuous culture in the presence of BLM (D/BlmIR and D/Blm40 cells). The resistance levels of the D/BlmII and D/Blm40 cells were 50- and 22-fold, respectively, determined at the EC50 level. The D/BlmI cells were only 2-fold resistant, whereas D/BlmIR cells were so resistant that almost no cytotoxicity was detected up to 200 microM BLM external concentration. Electropermeabilization was used in an attempt to bypass the plasma membrane of the cells and permit the distinction between internal resistance and membrane resistance. The former was observed when the products of the transfected genes were present. With respect to membrane resistance, differences were detected in the number of BLM-binding sites in several mutant cell lines, which could account for the differences in cell sensitivity to BLM. This suggests that the BLM-binding sites found at the cell surface may play a crucial role in BLM internalization and consequently in its cytotoxicity.

Facial sensibility in adolescents born with cleft lip after undergoing repair in infancy.

Values for facial sensibility measured in 68 adolescents born with cleft lip who had undergone repair in infancy (39 unilateral cleft patients with a mean age of 17 years and 29 bilateral cleft patients with a mean age of 19 years) were compared to values of 22 noncleft controls (mean age 18 years). Static two-point discrimination results and cutaneous pressure thresholds were similar between controls and cleft patients. Vibratory threshold values were lower in cleft patients, with significant differences (p < 0.05) in the nasolabial and upper lip skin areas. These differences might indicate minor sensory abnormalities of the quickly adapting fibers, differences in the ability of the deformed maxillary bone of cleft patients to conduct impulses, or other potential errors in the vibrometer.

Frontonasal and craniofrontonasal dysplasia: preoperative quantitative description of the cranio-orbito-zygomatic region based on computed and conventional tomography.

The unoperated crano-orbito-zygomatic complex of 18 children (mean 4.7 years) with frontonasal dysplasia (FND) and 12 children (mean 1.1 years) with crainofrontonasal dysplasia (CFND) was quantified by 15 standard measurements performed on either computed tomography scans or facial tomograms. The results were compared with age-matched control values. In the FND group, the mean anterior interorbital and mid-interorbital distances were significantly increased at 148% and 118% of normal, and in the CFND patients, at 177% and 140% of normal. Excessive medial orbital wall protrusion (mean, 145% of normal in FND and 177% in CFND), shortened zygomatic arch lengths (mean, 94% of normal in FND and 91% in CFND), and reduced cephalic lengths (mean, 96% of normal in FND and 83% in CFND) were all observed. An expanded interzygomatic buttress distance was documented only in the CFND group, at 11% of normal. The clinical presentation of craniofacial deformities such as FND and CFND can be objectively described by a numerical analysis of the bony pathology.

Electropermeabilization of cells in tissues assessed by the qualitative and quantitative electroloading of bleomycin.

Using cells in suspension, electropermeabilization is a technique extensively used to transfect living cells or to introduce a variety of compounds inside the cells. Here we demonstrate the reality of the tissue electropermeabilization using qualitative and quantitative determinations of the electroloading of bleomycin considered as an nonpermeant molecule that serves as an indicator of the permeabilization. In tissues, cell electropermeabilization is achieved for electric field intensities lower than those necessary to permeabilize the same cells in suspension. We also emphasize the importance of the geometry of the electric field lines defined by the electrodes for permeabilizing a whole tissue, for example a tumor.