Chronic hepatitis C infection: influence of the viral load, genotypes, and GBV-C/HGV coinfection on the severity of the disease in a Brazilian population

The distributions of the different genotypes of the hepatitis C virus (HCV) and GBV-C virus (GBV-C/HGV) vary geographically and information worldwide is still incomplete. In particular, there are few data on the distribution of genotypes (and their relationship to the severity of liver disease) in South America. Findings are described in 114 consecutive patients from Northeast Brazil (median age 52 years, range 18-72 years) who had abnormal levels of serum aminotransferases and seropositivity for HCV RNA. The patients were recruited from an outpatient clinic between November 1997 and April 1998. Quantitative HCV RNA and GBV-C/HGV RNA estimations were carried out by double-nested polymerase chain reaction (PCR) using primers from the 5'-untranslated regions (UTRs) of the genomes. HCV genotypes were determined by restriction fragment length polymorphism (RFLP) analysis with 5'-UTR primers and by PCR with type-specific 5'-UTR primers. GBV-C/HGV-RNA genotypes were determined by RFLP with specific 5'-UTR primers and phylogenetic trees were constructed using the Neighbour-Joining and Drawtree programs. Histological features were graded and staged according to international criteria. Of the 114 patients, 35 (30.7%) patients had cirrhosis and 22 (27.8%) had mild, 51 (64.6%) had moderate, and 6 (7.6%) had severe chronic hepatitis. Median HCV viral load was 10(6) genome equivalents per millilitre (range 10(4)-10(9)/ml). Frequencies of genotypes were 5.3% type 1a, 44.7% type 1b, 3.5% type 2, 41.2% type 3, and 5.3% mixed types. GBV-C/HGV-RNA was detected in the sera of 12 (10.5%) patients and was distributed among three phylogenetic groups. There were no significant differences between patients with the predominant HCV genotypes (1b and 3) with respect to gender, age group, viral load, severity of liver disease, or coinfection with GBV-C/HGV.     

Association between p.Leu54Met polymorphism at the paraoxonase-1 gene and plantar fascia thickness in young subjects with type 1 diabetes

OBJECTIVE— In type 1 diabetes, plantar fascia, a collagen-rich tissue, is susceptible to glycation and oxidation. Paraoxonase-1 (PON1) is an HDL-bound antioxidant enzyme. PON1 polymorphisms have been associated with susceptibility to macro- and microvascular complications. We investigated the relationship between plantar fascia thickness (PFT) and PON1 gene variants, p.Leu54Met, p.Gln192Arg, and c.-107C>T, in type 1 diabetes.RESEARCH DESIGN AND METHODS—This was a cross-sectional study of 331 adolescents with type 1 diabetes (162 male and 169 female). PFT was assessed by ultrasound, PON1 was assessed by genotyping with PCR and restriction fragment–length polymorphism, and serum PON1 activity was assessed by rates of hydrolysis of paraoxon and phenylacetate.RESULTS—Median (interquartile range) age was 15.4 (13.5–17.3) years, and diabetes duration was 7.6 (4.9–10.6) years. The distribution of p.Leu54Met genotypes was LL 135 (40.8%), ML 149 (45%), and MM 47 (14.2%). PFT was abnormal (>1.7 mm) in 159 adolescents (48%). In multivariate analysis, predictors of abnormal PFT were ML/LL versus MM p.Leu54Met polymorphism (odds ratio 3.84 [95% CI 1.49–9.82], P = 0.005); BMI (percentile) (1.02 [1.01–1.03], P = 0.007); systolic blood pressure (percentile) (1.01 [1.00–1.02], P = 0.03); and male sex (3.29 [1.98–5.46], P < 0.001).CONCLUSIONS—Thickening of the plantar aponeurosis occurs predominantly in overweight and male adolescents with type 1 diabetes. The MM genotype at PON1 p.Leu54Met is associated with a reduced risk of abnormal PFT.Paraoxonase-1 (PON1) is a calcium-dependent HDL-associated enzyme that protects LDLs from oxidation. In type 1 diabetic patients, the serum paraoxonase concentration is lower and HDL is a less efficient antioxidant than in healthy individuals (1). Oxidized LDL is implicated in the pathogenesis of atherosclerosis, diabetic retinopathy, and nephropathy (2). Variations in lipoprotein-related enzymes and genotypes may also promote diabetic microvascular damage (3).Soft-tissue thickening is associated with chronic hyperglycemia and is hypothesized to be due to collagen glycation (4). With use of ultrasound techniques to measure plantar aponeurosis, a collagen-rich tissue, researchers demonstrated previously that people with diabetes have increased plantar fascia thickness (PFT) (5). Recently, this group reported that increased PFT predicted the development of microvascular complications in adolescents with type 1 diabetes and proposed abnormal PFT as a putative marker of soft-tissue glycation (6).The PON gene cluster maps to chromosome 7q21-22 and influences gene expression and serum activity. There is an established link between PON1 and macrovascular disease (7) and emerging evidence linking PON1 to microvascular complications (8,9). In this study we investigated whether the variants c.-107C>T at the promoter region and p.Leu54Met and p.Gln192Arg at the coding regions of PON1 are associated with PFT in type 1 diabetes.     

Converting an IVF cycle to IUI in low responders with at least 2 follicles

OBJECTIVE: To assess the utility of transforming an in vitro fertilization (IVF) cycle with low ovarian response to an intrauterine insemination (IUI) cycle. STUDY DESIGN: The inclusion criteria were women undergoing IVF because of idiopathic infertility, a mild to moderate male factor or IUI failure, with at least 1 normal, patent tube. When ovarian stimulation produced 2-4 follicles > or = 18 mm, the IVF cycle was converted to an IUI cycle. In cases with 4 follicles, estradiol had to be < 800 pg/mL. A total of 57 cycles were analyzed. RESULTS: The clinical pregnancy rate (PR) was 14.0% (8/57) in IVF cycles converted to IUI vs. 17.3% in our general IUI population (240/1,389). Converted cycles were associated with longer ovarian stimulation and with lower estradiol levels and less mature follicles than was IUI in the general population. There was a trend toward higher PR in women starting ovarian stimulation with 225 IU of gonadotropins (18.2%) than in those starting with higher doses (8.6%) (P > .05). CONCLUSION: In IVF low responders with at least 1 normal, patent tube when 2-4 follicles are observed, converting the IVF cycle to an IUI cycle yields a PR of 14.0%. This option should be considered in the management of low responders, especially those not stimulated with high doses of gonadotropins.     

Surface Treated Catheters with Ion Beam Based Process for Blood Access

Abstract: Infection, thrombosis, and stenosis are among the most frequent complications associated with blood contacting catheters. Because these problems are usually related to surface properties of the base catheter material, surface treatment processes such as ion implantation and ion beam assisted deposition (IBAD) (silver based coatings) can be used to mitigate such complications. Because these ion beam based processes affect only the near‐surface region (approximately the outer 1 μm), there is little effect on bulk material properties. This study evaluated silver coated large bore catheters used for extracorporeal detoxification. In a 135 patient prospective study, 170 large bore catheters were inserted into the internal jugular or subclavian veins. Seventy‐eight surface treated catheters (Spi‐Argent, Spire Corporation, Bedford, MA, U.S.A.; n = 32 acute catheters, n = 46 long‐term catheters) were inserted in 55 patients. Ninety‐two untreated catheters placed in 80 patients served as controls (n = 40 acute catheters, n = 52 long‐term catheters). After removal, the catheters were cultured for bacterial colonization using standard microbiologic assays. They also were examined using a scanning electron microscope (SEM). Bacterial colonization was observed in 7% of the treated catheters compared with 35.3% of untreated catheters. The SEM investigations showed all treated catheters to possess low thrombogenicity. Results of the study indicate that ion beam based processes can be used to improve thrombus and infection resistance of blood contacting catheters.     

Benefits of minocycline and rifampin-impregnated central venous catheters

Objective To determine the efficacy of minocycline and rifampin-impregnated catheters compared to non-impregnated catheters in critically ill patients.Design Prospective, randomized, double-blind, controlled, multicenter trial.Setting Intensive care units of seven acute-care teaching hospitals in Spain.Patients Intensive care unit patients requiring triple-lumen central venous catheter for more than 3 days.Interventions At catheter insertion, 228 patients were randomized to minocycline and rifampin-impregnated catheters and 237 to non-impregnated catheters. Skin, catheter tip, subcutaneous segment, hub cultures, peripheral blood and infusate cultures were performed at catheter withdrawal. The rate of colonization, catheter-related bloodstream infection (CRBSI) and catheter-related clinical infectious complications (purulence at the insertion site or CRBSI) were assessed.Measurements and main results In the intention-to-treat analysis (primary analysis), the episodes per 1000 catheter days of clinical infectious complications decreased from 8.6 to 5.7 (RR =0.67, 95% CI 0.31–1.44), CRBSI from 5.9 to 3.1 (RR =0.53, 95% CI 0.2–1.44) and tip colonization from 24 to 10.4 (RR =0.43, 95% CI 0.26–0.73). Antimicrobial-impregnated catheters were associated with a significant decrease of coagulase-negative staphylococci colonization (RR =0.24, 95% CI 0.13–0.45) and a significant increase of Candida spp. colonization (RR =5.84, 95% CI 1.31–26.1).Conclusions The use of antimicrobial-impregnated catheters was associated with a significantly lower rate of coagulase-negative staphylococci colonization and a significant increase in Candida spp. colonization, although a decrease in CRBSI, increase in 30-day survival or reduced length of stay was not observed.Electronic Supplementary Material Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00134-004-2378-2This study was supported by a grant from Cook Europe.     

Intrapericardial Treatment of Neoplastic Pericardial Effusions

Pericardial effusion and cardiac tamponade are known complications of many advanced malignancies as lung cancer, breast cancer, lymphomas and leukemias. Initial relief can be easily obtained with percutaneous echo-guided pericardiocentesis, without significant mortality and morbidity and well-tolerated even in critically ill patients. Effusion recurrences can be observed, however, in up to 40% of cases if only simple pericardial drainage is performed. Effective management can be obtained by instillation in the pericardial sac of different agents, with sclerosing or cytostatic activity, like tetracyclines, bleomycin, thiotepa or radionuclides. Intrapericardial sclerotherapy is associated to good results in terms of recurrence prevention and survival improvement. Absence of pericardial effusion at 30 days after drainage can be observed in 70 to 90% of all treated patients, without significant variations among different treatments. No significant side effects are observed, with the exclusion of chest pain during tetracyclines instillation. In our opinion pericardiocentesis associated to intrapericardial sclerotherapy with thiotepa is the best compromise in terms of recurrence prevention, tolerability and costs. Real randomized, case-control studies are moreover required to assess the gold standard of malignant pericardial effusions treatment. Zusammenfassung Perikarderguss und Herzbeuteltamponade finden sich nicht selten als Folge fortgeschrittener maligner Erkrankungen, wie zum Beispiel bei Bronchial- und Mammakarzinomen sowie bei Lymphomen und Leukämien. Eine vorübergehende Entlastund kann durch die perkutane ultraschall- oder durchleuchtungskontrollierte Perikardpunktion erreicht werden. Dieses Vorgehen wird auch von schwer kranken Patienten gut toleriert und ist mit keiner nennenswerten Morbidität oder Mortalität verbunden. Allerdings werden Rezidive in bis zu 40% der Fälle beobachtet. Deshalb wurden bislang drei wesentliche alternative Vorgehensweisen entwickelt: 1. eine Perikardpunktion mit intraperikardialer Sklerotherapie, 2. eine perkutane Ballonperikardiotomie und 3. die operative Perikardfensterung entweder als subxyphoidale oder transthorakale Perikardiotomie oder als thorakoskopische Perikardfensterung. Zwar wird das chirurgische Vorgehen in der chirurgischen Literatur favorisiert, dagegen empfehlen kardiologische Zentren vor allem bei kritisch kranken Patienten ein kardiologisches Vorgehen mit Perikardpunktion und Sklerotherapie. Offensichtlich ist eine intraperikardiale Skerotherapie wesentlich schonender als das chirurgische Vorgehen. Außerdem wird hierdurch auch die Verschleppung von Tumorzellen in Pleura und Peritoneum vermieden. Unter intraperikardialer Sklerotherapie versteht man die Instillation von Substanzen, die sklerosierende und zytostatische Aktivität besitzen, wie zum Beispiel Tetracycline, Bleomycin, Thiotepa, Cisplatin oder Radionuklide. Tetracycline: Maher et al. konnten in einer größeren retrospektiven Studie zeigen, dass von 85 mittels Sklerotherapie behandelten Patienten 79% in den ersten 30 Tagen ohne Rezidiv blieben. Die Therapie mit Tetracyclinen ist allerdings mit einer hohen Nebenwirkungsrate verbunden: Fieber und Vorhofarrhythmien werden in 10%, retrosternale Schmerzen in 20% der Fälle beobachtet. Deshalb wird zur pH-Neutralisierung die Beimengung von Blut in das intraperikardiale Instillat empfohlen. Bleomycin: Liu et al. untersuchten 29 Patienten retrospektiv, die mit Bleomycin oder Doxycyclin behandelt wurden. Die Wirksamkeit beider Substanzen war ähnlich, Bleomycin wurde aber besser toleriert. Größere prospektive Studien fehlen. Thiotepa (Triethylenphosphoramid): Thiotepa ist eine alkylierende Substanz, die über lange Zeit in der Therapie von soliden Tumoren und Pleuraergüssen eingesetzt wurde, da sie sowohl sklerosierende als auch zytostatische Eigenschaften besitzt. Girardi et al. und Colleoni et al. behandelten insgesamt 60 Patienten mit verschiedenen Therapieregimen. Wesentliche Komplikationen oder Nebenwirkungen wurden nicht berichtet. Die Rezidivrate 30 Tage nach der Behandlung betrug 83%. Cisplatin: Zahlreiche Studien zeigen einen Therapieerfolg bei malignen intraperitonealen Ergüssen. Mehrere Studien wurden auch zur Behandlung von Perikardergüssen publiziert. Die Wirksamkeit mit rezidivfreien Intervallen von zwei bis 24 Monaten (Median zwei bis drei Monate) ist gut, die Nebenwirkungsrate sehr niedrig. Andere Medikamente: Weitere Therapievorschläge umfassen die Immunmodulatoren (IFN, Il-2, OK 432) oder anderen zytostatischen Substanzen (5-FU oder Aclarubicine). Radiotherapie: Insbesondere für die Therapie radiosensitiver Tumoren wurde eine externe Radiotherapie vorgeschlagen. Auch die intraperikardiale Applikation von ³²P-Kolloid ist mit sehr guten Ansprechraten (komplette Remission in 95% im Mittel für acht Monate) ohne signifikante Nebenwirkungen vergesellschaftet. Aufgrund der Datenlage kann eine allgemeine Empfehlung zur Therapie maligner Perikardergüsse gegenwärtig noch nicht gegeben werden. Dazu fehlen randomisierte, kontrollierte Multicenterstudien mit ausreichend großen Fallzahlen. Unserer Auffassung nach ist aber die Perikardpunktion in Kombination mit einer intraperikardialen Sklerotherapie, zum Beispiel mit Thiotepa oder Cisplatin, den chirurgischen Verfahren vorzuziehen, da Rezidiv- und Komplikationsraten sowie die Kosten gering sind.     

Clinical Evidence on a Novel Macrohybrid Design Dental Implant with 12° Angled Platform: A Systematic Review

Background: Immediate implant placement with immediate esthetics has become a more common procedure over time, though ensuring good emergence of the axis of the implant has been a challenge. A novel macroimplant design with an angled platform (Co-Axis^®) has been developed to ensure exit of the head of the implant in the correct prosthetic position. A systematic literature review was carried to determine the survival rate and marginal bone loss associated with these implants. Material and Methods: An electronic and manual literature search was made in accordance with the PRISMA statement. The search strategy was limited to human studies, retrospective and prospective clinical trials, cross-sectional studies, and cohort studies reporting outcomes of a novel macrohybrid implant with a 12° angled implant connection. Results: Three articles met the inclusion criteria and were reviewed in the analysis. The estimated success rate was 95.9%. The global marginal bone loss was estimated to be −0.17 ± 0.58 mm in an environment characterized by great heterogeneity (I² = 99%). The estimated mean implant stability was 69.6 ± 0.92 (ISQ). As only two studies provided the required information, it was not possible to determine publication bias. Lastly, mean recession was estimated to be practically zero (0.06 ± 0.23 mm), with great heterogeneity. Conclusions: Within the limitations of this systematic review, it can be affirmed that immediate implant treatment with Co-Axis^® implants shows a survival rate of 95.9% at one year of follow-up, with low marginal bone loss values, near-zero soft tissue recession, and favorable papilla index values. Nevertheless, the great heterogeneity of the data requires the findings to be interpreted with caution.     

Human Sleep Apneas and Animal Diving Reflexes: The Comparative Link

Adaptations to survive periods of limited access to oxygen should have been favored along the evolution of vertebrates. Paradigmatic examples of this adaptation are the diving animals, which can sustain prolonged and repetitive periods of anoxia. These animals support what would be considered a severe gas imbalance in their internal environment thanks to three main strategies: increased oxygen stores, resistance to asphyxia, and reduced metabolic expenditure during the apneic intervals. However, diving animals developed their abilities from very old life-sustaining responses that should have been used on many other occasions. Humans with sleep apneas perhaps share many physiological adaptations with diving animals. We review here the extent of such similarities and offer clear evidence of its existence and suggest possible research lines that could improve the clinical knowledge about this condition.