Hospitalization for vitamin-K-antagonist-related bleeding: treatment patterns and outcome.

BACKGROUND: Bleeding complications are common side effects of vitamin-K antagonist (VKA) therapy. Data on the in-hospital management and outcomes of these bleeding events are scarce and information is mostly derived from trial cohorts. OBJECTIVES: The objective was to collect data on the management and clinical outcome of hospitalizations owing to VKA-related bleeding in real-world practice. PATIENTS AND METHODS: We performed a multicenter observational cohort study involving 21 secondary and tertiary care hospitals in the administrative district Dresden, Saxony, Germany throughout the year 2005. All consenting patients presenting with VKA-related bleeding complications were included. No exclusion criteria applied. Data were collected at admission, at discharge and at 90 days to evaluate resource consumption, length of hospital stay and risk factors for in-hospital- and 3-month mortality. RESULTS: Two hundred and ninety patients were included (median age 74 years; 50.7% male). The main indications for VKA therapy were atrial fibrillation (63.4%), prior thromboembolism (18.6%) and mechanical heart valves (11.4%), and most common bleeding localizations were large hematoma (23.1%), upper gastrointestinal (GI) tract (17.9%) and intracranial bleeding (14.1%). On hospital admission, the median International Normalized Ratio (INR) was 3.0 (range 0.9-12.5, interquartile range [IQR] 2.1-3.9). In-hospital mortality was 7.6% with impaired renal function as the most relevant risk factor. At 90 days mortality was 14.1% and 15.3% of survivors were help-dependent. CONCLUSIONS: VKA-related bleeding leading to hospitalization is associated with long hospitalization, relevant resource utilization, high mortality or persistent sequlae. Patient-related factors such as impaired renal function, chronic cardiac or pulmonary disease and dementia are predictive of in-hospital and 3-month mortality.

Desmopressin testing in haemophilia A patients and carriers: results of a multi centre survey.

INTRODUCTION: Desmopressin (DDAVP) testing (DT) in patients (pts) with haemophilia A (HA) and carriers (CHA) is up to now not standardized. This prompted us to evaluate results of DT carried out between 1996 and 2011 in centres of the Competence Network Haemorrhagic Diatheses East. PATIENTS AND METHOD: An increase of the factor VIII activity (FVIII) above 50% or at least the two fold of initial values within 120 min after DDAVP was defined as complete response (CR). Data from 80 patients (31 children, 49 adults) of whom 64 suffered from HA (sub-HA: n=48; mild: n=14; moderate: n=2) and 16 patients CHA were evaluated. RESULTS: In 34 patients DDAVP was given i.v. (dose range: 0.26-0.6 µg/kg body weight, mean: 0.33), in 31 intranasally (i.n. 300-600 µg) and in 15 s.c. (15-40 µg). The maximal FVIII increase was reached 60 min after DDAVP. For i.v. application the mean FVIII increase was 3.1-fold, for i.n. 2.1-fold and for s.c. 2.4-fold. A CR was detected in 71 patients, a non-response in 9. Mild side effects such as flush, headaches or nausea were observed in 11 patients (14%). CONCLUSION: For desmopressin testing in patients with haemophilia A and carriers i.v. application at 0.3 µg/kg body weight and the determination of FVIII before and 60 min after desmopressin infusion is recommended.

Efficacy and safety of rivaroxaban or fondaparinux thromboprophylaxis in major orthopedic surgery: findings from the ORTHO-TEP registry.

BACKGROUND: Thromboprophylaxis with rivaroxaban (R) is superior to enoxaparin in patients undergoing major orthopedic surgery (MOS). However, rivaroxaban has never been directly compared with fondaparinux (F), which also shows superior efficacy over enoxaparin. The clinical impact of switching from fondaparinux to rivaroxaban thromboprophylaxis is unclear. OBJECTIVES: To evaluate the efficacy and safety of rivaroxaban or fondaparinux thromboprophylaxis in unselected patients undergoing MOS. PATIENTS/METHODS: This is a monocentric, retrospective cohort study in 5061 consecutive patients undergoing MOS at our centre, comparing rates of symptomatic VTE, bleeding and surgical complications, length of hospital stay and risk factors for VTE. RESULTS: Rates of symptomatic VTE were 5.6% (F) and 2.1% (R; P < 0.001), with rates for distal DVT being 3.9 vs. 1.1% (P < 0.001). Rates of major VTE were numerically higher with fondaparinux (1.8 vs. 1.1%), but not statistically significant. Rates of severe bleeding (bleeding leading to surgical revision or death, occurring in a critical site, or transfusion of at least two units of packed red blood cells) were statistically lower with rivaroxaban compared with fondaparinux (2.9 vs. 4.9%; P = 0.010). The mean length of hospital stay was significantly shorter in the rivaroxaban group (8.3 days, 95% CI 8.1-8.5 vs. 9.3 days, 9.1-9.5; P < 0.001). CONCLUSION: Based on an indirect comparison of two consecutive cohorts, our data suggest that thromboprophylaxis with rivaroxaban is associated with less VTE and bleeding events than fondaparinux in unselected patients undergoing MOS. Prospective comparisons are warranted to confirm our findings.

Central adjudication of venous ultrasound in VTE screening trials: reasons for failure.

BACKGROUND: The accuracy of screening ultrasound for venous thrombosis in asymptomatic patients is still a matter of debate. The VENUS study evaluated the accuracy of centrally adjudicated venous ultrasound against venography in patients after major orthopedic surgery and found the sensitivity of ultrasound to be poor for both proximal and distal deep vein thrombus (DVT). OBJECTIVES: To evaluate whether thrombus characteristics such as location or size influence the diagnostic performance of centrally adjudicated venous ultrasound. METHODS: All false negative sonograms of the VENUS study were re-evaluated against the corresponding venograms. Discrepancies were categorized into types of diagnostic failures. Within these categories, thrombus characteristics such as location, length or size of thrombus were evaluated. RESULTS: One hundred and twelve pairs of discrepant ultrasound and venography documents were compared with 28 pairs with concordant results. Discrepancies were caused by local documentation failure (37.5%), failure of the ultrasound method (43.7%) and failure of the central adjudication process (18.7%). The overall size of thrombi was small, which caused about 40% of all sonographic failures with a detection threshold of five Marder points, a thrombus length of 9.5 cm and a number of 3.5 pathological compression manoeuvres. Proximal or distal location of DVT did not affect thrombus detection. CONCLUSION: If centrally adjudicated ultrasound is to be used in future VTE screening trials, training of local sonographers and central adjudicators needs to be intensified, because asymptomatic DVTs seem to be small and ultrasound sensitivity depends on the number of pathological compression manoeuvres documented in the ultrasound document. In contrast, distal or proximal thrombus location itself does not influence sensitivity.

Intragastric acidity during administration of generic omeprazole or esomeprazole - a randomised, two-way crossover study including CYP2C19 genotyping.

BACKGROUND: Generic omeprazole has been approved in many countries for the treatment of acid-related gastrointestinal disorders. However, clinical studies comparing generic to original proton pump inhibitors are limited. AIMS: To compare the effect of generic omeprazole 20 mg/day with esomeprazole 20 mg/day on intragastric acidity and to investigate the influence of the CYP2C19 metabolizer status. METHODS: In this randomised, single-blinded, two-way crossover study, 24 healthy Helicobacter pylori-negative subjects, received generic omeprazole (Omep; Hexal AG, Holzkirchen, Germany) 20 mg once daily or esomeprazole 20 mg once daily for five consecutive days. Twenty-four-hour intragastric pH was recorded on day 5 of each treatment. CYP2C19 status was determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Over all, there were no statistically significant differences between generic omeprazole and esomeprazole with respect to median intragastric pH (3.5 and 3.9, P = 0.07), the total hours with intragastric pH >4 (10.4 and 11.3, P = 0.29), and during upright (9.6 and 9.1, P = 0.77) or supine (2.2 and 2.2, P = 0.94) position. However, in CYP2C19 rapid metabolizers, esomeprazole was superior to omeprazole, with the percentage of time with intragastric pH >3.0 and pH >3.5 being higher with esomeprazole than with generic omeprazole [Δ = 9% (P = 0.026) and Δ = 8% (P = 0.046), respectively]. CONCLUSIONS: Overall, generic omeprazole 20 mg appears to provide a similar intragastric acid control when compared with esomeprazole 20 mg. However, esomeprazole might be advantageous in subjects with a rapid CYP2C19 metabolizer status.

Impaired insulin turnover in islets from type 2 diabetic patients.

Failure of pancreatic ß-cells contributes to the development of type 2 diabetes. Besides evidence of reduced glucose-stimulated insulin secretion and ß-cell mass, little information is available about the molecular deficits of human diabetic islets. Islets were isolated from macroscopically normal pancreatic tissue from 8 patients with type 2 diabetes and 17 matched non-diabetic patients who underwent pancreatic surgery. Insulin content and insulin secretion were measured before and after islet stimulation with 25 mM glucose for 2 hours. In parallel, we also investigated the subcellular localization of polypyrimidine tract-binding protein 1 (PTBP1), whose nucleocytoplasmic translocation is involved in the rapid posttranscriptional up-regulation of insulin biosynthesis following islet stimulation with glucose and GLP-1. Glucose stimulated insulin secretion was decreased, albeit not significantly, in type 2 diabetic islets compared to non-diabetic islets. Stimulation increased the total amount of insulin (islet insulin content + secreted insulin) in islet preparation from non-diabetic patients, but not from type 2 diabetic subjects. Furthermore, the nuclear levels of PTBP1 were decreased in stimulated non-diabetic islets, but not in type 2 diabetic islets. These results suggest that impairment of rapid insulin increase in response to glucose is a specific trait of type 2 diabetic islets. Nuclear retention of PTBP1 is likely to play a role in this deficit, which in turn can contribute to impaired insulin secretion in type 2 diabetes. Overall, these data highlight the importance of investigating mechanisms of insulin biosynthesis and degradation to gain insight into the pathogenesis of type 2 diabetes.

Platelet function in obese children and adolescents.

UNLABELLED: Platelet hyperaggregability contributes to thromboembolic events of obesity in adulthood. In obese children hyperaggregability was described in platelet rich plasma. We investigated platelet aggregation in children with obesity and lipometabolic disorders in whole blood. PATIENTS, MATERIAL, METHODS: Specimens from patients with overweight (n = 35), hypercholesterolaemia and normal weight (n = 5), overweight plus combined lipometabolic disorder (n = 5) and healthy controls (n = 20) were investigated. Aggregation and ATP release were induced by ADP (20 µmol/l), collagen (1 µg/ml) and thrombin (0.5 U/ml) using a lumiaggregometer. RESULTS: Overweight children and normal weight patients with hypercholesterolaemia exhibited no significant differences in platelet aggregation compared to controls. Contrastingly, in patients with obesity plus lipometabolic disorder the aggregation rate was significantly higher (p < 0.05) suggesting a hyperaggregable state. CONCLUSION: Obviously in obese children a hypercoagulable state exists and the slight hyperaggregability observed in whole blood in this cohort might contribute to that. Any effort should be undertaken to avoid obesity in children especially in those countries where the prevalence of obesity in childhood is continuously increasing.

[Evaluation of haemostasis in children treated with valproic acid]. / Untersuchungen zur Hämostase bei Kindern unter Valproatbehandlung.

UNLABELLED: Coagulation parameters were determined in children with valproic acid mono- and valproic acid-lamotrigin combination therapy. PATIENTS, METHODS: Monotherapy group (n = 22; mean age: 10.5 years) was compared to combination therapy (n = 7; 12.9 years) and a control group (n = 22; 8.7 years). The following parameters were measured: aggregation and ATP-release in whole blood (ADP: 20 µmol/l, collagen: 1 µg/ml, thrombin: 0.5 U/ml), PFA-100® closure times (CT), blood cell counts, global tests, VWF:Ag, VWF:CBA, factors VIII and XIII as well as fibrinogen. Bleeding symptoms were evaluated by using a questionnaire. RESULTS: For ADP- and collagen-induced aggregation as well as for ATP release no significant differences between the groups were detected. The combined therapy group showed significantly prolonged CT. Von Willebrand disease was not detected in any of the patients. The platelet count was significantly decreased in the monotherapy group. In six children a mild bleeding tendency was observed, mostly epistaxis. CONCLUSION: A clinically relevant influence of valproic acid on haemostasis was found only in few cases. However, before surgical procedures an extended coagulation diagnostics is recommended in patients with valproic acid therapy.

Comparison of zirconia and titanium implants after a short healing period. A pilot study in minipigs.

The aim of this animal study was to investigate and compare the osseointegration of zirconia and titanium dental implants. 14 one-piece zirconia implants and 7 titanium implants were inserted into the mandibles of 7 minipigs. The zirconia implants were alternately placed submerged and non-submerged. To enable submerged healing, the supraosseous part was removed, using a diamond saw. The titanium implants were all placed submerged. After a healing period of 4 weeks, a histological analysis of the soft and hard tissue and a histomorphometric analysis of the bone-implant contact (BIC) and relative peri-implant bone-volume density (rBVD; relation to bone-volume density of the host bone) was performed. Two zirconia implants were found to be loose. All other implants were available for evaluation. For submerged zirconia and titanium implants, the implant surface showed an intimate connection to the neighbouring bone, with both types achieving a BIC of 53%. For the non-submerged zirconia implants, some crestal epithelial downgrowth could be detected, with a resultant BIC of 48%. Highest rBVD values were found for submerged zirconia (80%), followed by titanium (74%) and non-submerged zirconia (63%). The results suggest that unloaded zirconia and titanium implants osseointegrate comparably, within the healing period studied.

[Desmopressin testing in children with von Willebrand syndrome in haemostaseologic centers of Saxonia, Saxonia-Anhalt and Thuringia]. / Desmopressin-Tests bei Kindern mit von-Willebrand-Syndrom in den Gerinnungszentren Sachsens, Sachsen-Anhalts und Thüringens.

The influence of desmopressin on hemostasis is mediated by the release of von Willebrand factor and of coagulation factor VIII from vascular endothelium. The necessity of testing desmopressin effectiveness on hemostasis is a matter of controversy and the performance of the test is not yet standardized. For this reason the desmopressin tests in 114 children with von Willebrand syndrome (type 1, n=98; type 2A, n=12; type 2M, n=2; type 2N, n=2) carried out in 7 paediatric haemostaseologic centers were retrospectively analyzed. The effectiveness of desmopressin was assessed using defined response criteria. As expected, the test performance showed a wide variation among the centers. In 99 children desmopressin was given intravenously as a short infusion at a dosage ranging from 0.25 to 0.41 microg/kg and in 15 intranasally at an absolute dose of 40 to 300 microg. The points of time for blood taking after desmopressin application ranged from 0.5 to 12 h. The absent desmopressin response in 7 patients (6%) and the partial response in 15 indicate the necessity of testing desmopressin effectiveness before the first therapeutic use. The application of desmopressin was well tolerated by the patients.

Acid production by oral strains of Candida albicans and lactobacilli.

Both Candida albicans and lactobacilli are common colonizers of carious lesions in children and adolescents. The purpose of this study is to compare the velocity of acid production between C. albicans and several Lactobacillus species at different pH levels and concentrations of glucose. Washed, pure resting-cell suspensions were obtained by culturing a total of 28 oral isolates comprising the species C. albicans, Lactobacillus rhamnosus, Lactobacillus paracasei paracasei, Lactobacillus paracasei tolerans and Lactobacillus delbrueckii lactis. Acid production from glucose was determined at a constant pH of 7.0, 5.5, 5.0 and 4.0 by repeated titrations with NaOH in an automated pH-stat system. Acid formation rates of yeast and lactobacilli proved to be similar at both neutral and low pH, while in a moderately acidic environment C. albicans produced less acid than the lactobacilli. Ion chromatographic analysis of the cell-free medium after titration revealed pyruvate to be the predominant organic acid anion secreted by C. albicans. The proportion of organic acids to overall acid production by the yeast was below 10% at neutral conditions, in contrast to 42-66% at pH 4.0. Compared to lactobacilli, yeast required a concentration of glucose that was about 50 times higher to allow acid production at half the maximum speed. Considering the clinical data in the literature about the frequency and proportions of microorganisms present in early childhood caries lesions, the contribution of oral lactobacilli as well as C. albicans to overall microbial acid formation appears to be important.

Incidence, risk profile and morphological pattern of venous thromboembolism after prostate cancer surgery.

BACKGROUND: Venous thromboembolism (VTE) is the most common non-surgical complication after major pelvic surgery. Little is known about the risk factors or the time of development of postoperative venous thrombosis. METHODS: A cohort of 523 consecutive patients undergoing radical prostatectomy with lymphadenectomy was prospectively assessed by complete compression ultrasound at days -1, +8 and +21. RESULTS: Complete data were available in 415 patients, while four patients had VTE before surgery and were excluded from the analysis. In the remaining 411 patients, 71 VTE events were found in 69 patients (16.8%). Most were limited to calf muscle veins (56.5%), followed by deep calf vein thrombosis (23.2%), proximal deep vein thrombosis (DVT, 14.5%) and pulmonary embolism (PE, 5.8%). Of the 14 patients with proximal DVT/PE, 11 patients (78.6%) developed VTE between days 8 and 21. Risk factors for VTE were a personal history of VTE (OR 3.0), pelvic lymphoceles (LCs) impairing venous flow (OR 2.8) and necessity of more than two units of red blood cells (OR 2.6). CONCLUSION: Venous thromboembolism is common after radical prostatectomy. A significant proportion develops after day 8, suggesting that prolonged heparin prophylaxis should be considered. Since LCs with venous flow reduction result in higher rates of VTE, hemodynamically relevant lymphoceles should be surgically treated.

Nitric oxide and endothelin after lipid apheresis - a pilot study.

OBJECTIVE: Patients with the heterozygous form of familial hypercholesterolemia (FH) display an early onset of atherosclerosis due to disturbed vascular-endothelial function. Whether the improvements of endothelial function after lipid apheresis are mediated by increased NO-production or by an altered turnover of vasoconstrictors such as ET-1 is still unknown. This was the onset of the present study. METHODS: Patients with FH and advanced atherosclerosis receiving regular LDL apheresis at 1 to 3 weeks were recruited. Lipids, L-arginine (L-Arg), L-hydroxyarginine (NHA), L-citrulline as well as big endothelin (Big-ET) and endothelin (ET-1) were measured after DALI, HELP and TheraSorb apheresis. RESULTS: 17 patients with severe FH aged 55.6 years (mean) received a total of 30 treatments. TC, LDL-C, HDL-C, TG and TC / HDL-C ratio were reduced (55, 70, 9, 48, and 52%; p<0.01) with no differences between apheresis systems. L-Arg was reduced after apheresis (HELP -18.0%, DALI -26.5%; Therasorb -7.6%) and returned to baseline after 2 h. Big-ET (p<0.01) and ET-1 were found to be increased directly and 2 hours after apheresis with HELP while transiently decreasing with DALI and Therasorb. CONCLUSION: Improvement of endothelial function after apheresis seems to have multifaceted causes. The further elucidation of the interrelationship between endothelial dysfunction and restricted NO synthesis, as addressed in this study by measuring L-NHA, L-Arg, L-Cit, ET-1 and Big-ET will be necessary in the future.

[Analysis of tissue inhibitor of metalloproteinase-2 gene polymorphisms in a caucasian population with abdominal aortic aneurysms]. / Analyse von Genvarianten des Gewebeinhibitors der Metalloproteinase-2 (TIMP-2) bei Patienten mit abdominalem Aortenaneurysma.

BACKGROUND: The formation of sporadic abdominal aortic aneurysm (AAA) is explained by a remodelling of the extracellular matrix (ECM) and breakdown of structural components of the vascular wall. Matrix metalloproteinases are the principle matrix-degrading proteases and are known to play a major role in the remodelling of the extracellular matrix in arterial vessels. Their activity is controlled by tissue inhibitors of metalloproteinases (TIMPs). Decreased TIMP-1 and TIMP-2 expression in the extracellular matrix of the walls of AAAs has been demonstrated in several studies. This case-control study was designed to investigate the possible impact of genetic variants of the TIMP-2 gene in the aetiology of AAA and to reproduce a recently described significant difference in allele frequency of the SNP 303G>A in a German population. METHODS: TIMP-2 single nucleotide polymorphisms (SNPs) were analysed in a study sample of 50 patients with AAA and 41 controls. Differences in genotype and allele frequencies of the identified polymorphisms were determined after sequencing the entire coding region and selected parts of the promoter using the automated laser fluorescence technique. RESULTS: Six polymorphisms were identified, one of which is described for the first time, located in the intron, (231+23C>T). An association of the SNP 303G>A with the phenotype was not confirmed in our study (p=0.648). However, the CT genotype of the SNP -479C>T was more frequent in patients with AAA than in the control group (p=0.054). CONCLUSIONS: In our analysis of the TIMP-2 gene, we identified one new SNP. A previously published association of the SNP 303G>A with the phenotype could not be validated in our population. However, we detected an association for the CT genotype of one polymorphism in the promoter region (g-479C>T) and AAA. This result has to be proved in a second study sample.

[Influence of packed red cell transfusions on blood selenium concentration in pediatric hemato-oncology]. / Einfluss der Transfusion von Erythrozytenkonzentrat auf die Selenkonzentration im Vollblut bei Kindern mit hämato-onkologischen Erkrankungen.

BACKGROUND: In humans approx. 10% of the total body selenium (Se) content is present in the blood being evenly distributed among plasma and red cells. The important role of Se in antioxidative biological pathways is proven. Many parents of children with malignancies ask for supplementation with Se as part of complementary therapy during or after the oncological treatment. However, toxic Se concentrations may easily be reached in children. In order to analyse whether Se is also supplied by red cell transfusions (RCT), we determined Se concentration in whole blood prior and after packed RCT in pediatric patients with hemato-oncological diseases. PATIENTS AND METHODS: EDTA-blood was collected from 17 patients (median age: 4 years, range: 1 month - 17 years) with aplastic anemia, acute leukemia and solid tumours prior and after RCT (n=60). Patients received a median of 2 transfusions (range: 1-14). Samples were also collected from the transfusion blood bags and Se concentration was determined quantitatively by atomic absorption spectrometry. RESULTS: 95% of the specimen collected from the transfusion bags exhibited selenium concentrations within the normal adult range. Mean Se concentration in the patients' blood prior to RCT was 66.2 microg/l (range: 38.0-166.4 microg/l) and increased to 70.7 microg/l (range: 14.1-105.1 microg/l) thereafter (statistically not significant). Applying age dependant reference values Se concentrations were below the lower limit in 45% of the samples prior to RCT and only in 26% after RCT. The reason for this increase was the fact that Se concentrations were often just marginally below the age-dependant lower limit prior to RCT and in the lower normal range thereafter. CONCLUSION: 43% of the patients with hemato-oncological diseases in this study exhibited no Se deficiency at any time point. In the remaining 57% of the patients a transient or persistent Se deficiency was detected with blood levels partially far below the lower threshold of the age adjusted normal range. The Se deficiency was corrected in four out of eight patients by RCT. As Se levels may fluctuate in individual pts a supplementation should only be initiated if based on regular monitoring of the Se concentration.

Evaluation of desmopressin effects on haemostasis in children with congenital bleeding disorders.

Desmopressin (DDAVP) affects haemostasis by the release of von Willebrand factor and coagulation factor VIII from endothelium. The aim of the study was to evaluate the results of DDAVP testing in paediatric patients with congenital bleeding disorders. Forty-one patients consisting of children with von Willebrand's disease (VWD, n = 26) and platelet function defects (PFD, n = 15) received DDAVP intravenously at a dosage of 0.3 mug/kg over 30 min. FVIII activity (FVIII), von Willebrand factor antigen (VWF:Ag), collagen-binding activity (VWF:CB) and PFA 100((R)) closure times (CT) were measured before, 60, 120 and 240 min after DDAVP. In VWD, the VWF:Ag increased threefold until 60 min and then it decreased continuously. Compared with baseline, VWF:Ag was significantly higher at 60 and 120 min but not at 240 min. In contrast, in PFD, the peak of VWF:Ag was reached after 120 min. Two hundred and forty minutes after DDAVP, the mean was still significantly elevated compared with baseline values. The course of VWF:CB corresponded to that of VWF:Ag. In patients with VWD and PFD, FVIII rose two- to threefold within 2 h after DDAVP. CT in patients with VWD shortened markedly within 120 min and then rose again. In all children with PFD, except one non-responder, the CT shortened within 240 min after DDAVP. Two non-responders with VWD were identified by the failed increase of VWF:Ag, VWF:CB and by prolonged CT. Haemostatic effects of DDAVP differ interindividually and dependent on the coagulation disorder. DDAVP was effective in most, but not in all patients. DDAVP testing is recommended to determine the individual haemostatic response.

Evaluation of osseointegration of dental implants coated with collagen, chondroitin sulphate and BMP-4: an animal study.

Various studies have shown type I collagen (coll) to increase bone-implant contact (BIC) compared to uncoated implants. The aim of this animal study was to test whether the integration of chondroitin sulphate (CS) and the growth factor rhBMP-4 into a collagenous coating could further increase the measured BIC compared to collagen coated implants alone. The experimental implants had two recesses along the length axis. 120 implants with the surface modifications: coll, coll/CS, coll/CS/rhBMP-4 were inserted into the mandible of 20 minipigs. Six months after implantation, BIC was measured histomorphometrically on the surface and within the recesses. Due to the specific animal model and strict criteria in placement, 39.2 % of the implants were considered as failure and not included in the analysis. Of the successfully gained 73 implants, the highest percentage of BIC was obtained for coll/CS (40%), followed by coll (30%) and coll/CS/rhBMP-4 (27%), P=0.013. BIC within the recesses was highest for coll/CS (51%), followed by coll (43%) and coll/CS/rhBMP-4 (34%), P=0.025. The result suggests that the inclusion of CS slightly increases the BIC compared to collagen coated implants. The further inclusion of a low amount rhBMP-4 had a detrimental effect on bone formation compared to coll/CS, P<0.05.

Failure of ascorbic acid to prevent contrast-media induced nephropathy in patients with renal dysfunction.

AIMS: Contrast-media induced nephropathy (CIN) remains a common complication after contrast dye exposure especially in patients with chronic renal impairment (CRI). We sought to evaluate the efficacy of the antioxidant ascorbic acid as an adjunct to hydration in limiting the incidence of contrast induced nephrotoxicity after coronary procedures. MATERIALS AND METHODS: In a randomized, double-blind, prospective, single center-study, 143 consecutive patients with CRI (creatinine level > 120 micromol/l) referred to coronary angiography/intervention were randomly assigned to receive 1 g ascorbic acid or placebo in adjunct to saline hydration prior to and after angiography. Creatinine and urea nitrogen levels were measured prior to and up to 6 days after exposure to contrast agent. RESULTS: The development of CIN occurred totally in 8/143 (5.6%) patients. Between the two groups no significant difference was detected (Vitamin C 5/74 (6.8%) patients; placebo 3/69 (4.3%) patients). After adjusting for the amount of contrast dye, drug treatment, cardiovascular risk factors, ejection fraction, or sex, again no differences were detected. No patient required dialysis. More patients with diabetes had development of CIN (7/85; 8.2%) compared with nondiabetic patients (1/58; 1.7%), although not significant (p = 0.14). The incidence of CIN was elevated in patients with high amounts (> 140 ml) of contrast volume used (6/8). CONCLUSIONS: Our study does not support the prophylactic use of ascorbic acid in patients with renal dysfunction exposed to contrast dye.

Reflection of bounce phenomenon in DPOAE: a human study.

The behavior of distortion product otoacoustic emission, DPOAE, has been studied in normally hearing subjects after application of a tone of 0.25-kHz frequency and of 80-dB nHL intensity during 3 min. The bounce phenomenon has correspondingly been investigated just in humans and just via the objective approach. The reliable augmentation of DPOAEs was observed at 0.5 min after the cessation of exposures, the amount of increments being statistically equal at different DPOAE frequencies, 0.75, 1, 1.5, and 2 kHz. At 2 and 4 min after the exposure, in contrast, DPOAE magnitudes were shown to be similar to those of pre-exposure recordings. The present DPOAE results were matched with the previous data on transiently evoked otoacoustic emission and no principal differences have been found between.

Interaural pitch perception difference: dependence upon internal and external factors.

Tone pulses were presented consecutively to one and the other ear in normally hearing musicians. The frequency of pulses in one, reference ear was fixed. That in the other, test ear varied to achieve the same pitch of tones in both ears. The frequency deviation of the test tone from the reference one was judged as the interaural pitch perception difference, IPPD. No dissimilarities in IPPDs were found between females and males. On the other hand, in both genders the IPPD scores were greater at higher than at medium and, especially, at lower tone frequencies, 2000, 1000, and 500 Hz, respectively. Also, the IPPDs displayed greater values when the reference tone was administered to the left ear, while the right ear served for the application of the test tone, LrRt, than when the reference tone was delivered to the right ear, while the test tone was applied to the left ear, RrLt. The IPPD differences under LrRt and RrLt stimulus presentations modes were prominent just at higher than at medium and, especially, at lower tone frequencies. The results are interpreted proceeding from the peculiar coding of low- and high-frequency acoustic information into brain auditory structures. Correspondingly, the IPPD is considered to be a consequence of central neural rather than of peripheral receptor events.