Analysis of the survival of permanent vascular access ports

Complications arising from vascular access are major causes of morbidity in patients on renal replacement therapy. They contribute to frustration of health care providers and to high medical cost. To prevent failures in the future it will be helpful to identify the factors that are related to vascular access, malfunction. In a retrospective analysis we analysed the types, duration and primary patency rate of 1,033 permanent vascular access in 544 consecutive patients established during a 13-year period in a tertiary care hospital. Patient characteristics, incidence and risk factors related to vascular access failure were registered. In addition vascular access outcomes in patients who started haemodialysis with a catheter and in whom initial vascular access failure occurred were analysed separately. Forty-five per cent of patients required a central catheter at the start of HD, but 92% of them were being dialysed with an a-v fistula at the last observation. The total number of complications was 0.24 episodes per patient per year at risk, and the rate of thrombosis 0.1. A total of 52% of patients were dialysed throughout the observation period with their initial a-v fistula; 9.3% had more than three episodes of vascular access failure. The radiocephalic a-v fistula was the access with the best median duration, exceeding 7 years, but also the type that had the highest initial failure rate, i.e. 25% of patients and 13% of events. The brachiocephalic a-v fistula was the second most frequent type of vascular access, with a median duration of function of 3.6 years, in contrast the humerobasilar a-v fistula, lasted on average over 5 years. Average patency of the different types of grafts did not exceed 1 year, with the exception of the autologous saphenous graft with a median duration of function of 1.4 years. Patients with glomerulonephritis had the best function rates for their access, the median duration exceeding the duration of the study, whereas in half of diabetic patients it was less than 1 year. The duration of patency of the vascular access was twice as long in patients below age 65 years and in elderly males compared to elderly females. Patients who start HD with a catheter, as well as those with initial vascular access failure, have a higher rate of access failure in the subsequent course on renal replacement therapy. In conclusion, the radiocephalic and the brachiocephalic a-v fistula are the two types of vascular access with the longest duration of function, although a high rate of initial failure is seen with the radiocephalic a-v fistula. Age, female gender, presence of diabetic nephropathy, start of dialysis with a catheter, and failure to wait for initial maturation of vascular access are risk factors, and account for the majority of vascular access failure during renal replacement therapy.     

Effects of somatostatin on renal function in cirrhosis.

To investigate the renal effects of somatostatin in cirrhosis, renal function and plasma and urinary levels of endogenous neurohumoral vasoactive substances were measured in conditions of intravenous water overload (20 mL/kg body wt with 5% glucose) before and during the intravenous infusion of somatostatin (250-500 micrograms/h) in 6 cirrhotic patients without ascites and 17 nonazotemic cirrhotic patients with ascites. Somatostatin induced a significant reduction of renal plasma flow, glomerular filtration rate, and free water clearance in both groups of patients. In patients with ascites, somatostatin also reduced urinary sodium excretion. Changes in renal function were significantly more marked in patients with ascites than in those without ascites and occurred in the absence of changes in mean arterial pressure and plasma levels of renin, aldosterone, norepinephrine, antidiuretic hormone, and atrial natriuretic peptide. Somatostatin induced a significant reduction in the plasma concentration of glucagon and urinary excretion of prostaglandin E2 that was not related to changes in renal function. These findings indicate that somatostatin administration induces renal vasoconstriction and impairs glomerular filtration rate, free water clearance, and sodium excretion in cirrhosis by a mechanism unrelated to systemic hemodynamics and endogenous neurohumoral vasoactive systems.     

Selection of medical treatment in stable angina pectoris: Results of the International Multicenter Angina Exercise (IMAGE) study

Objectives. The present study was designed to investigate which characteristics of anginal symptoms or exercise test results could predict the favorable anti-ischemic effect of the beta-adrenergic blocking agent metoprolol and the calcium antagonist nifedipine in patients with stable angina pectoris.

Background. The characteristics of anginal symptoms and the results of exercise testing are considered of great importance for selecting medical treatment in patients with chronic stable angina pectoris. However, little information is available on how this first evaluation may be used to select the best pharmacologic approach in individual patients.

Methods. In this prospective multicenter study, 280 patients with stable angina pectoris were enrolled in 25 European centers. After baseline evaluation, consisting of an exercise test and a questionnaire investigating patients' anginal symptoms, the patients were randomly allocated to double-blind treatment for 6 weeks with either metoprolol (Controlled Release, 200 mg once daily) or nifedipine (Retard, 20 mg twice daily) according to a parallel group design. At the end of this period, exercise tests were repeated 1 to 4 after drug intake.

Results. Both metoprolol and nifedipine prolonged exercise tolerance over baseline levels; the improvement was greater in the patients receiving metoprolol (p < 0.05). Multivariate analysis revealed that low exercise tolerance was the only variable associated with a more favorable effect within each treatment group. Metoprolol was more effective than nifedipine in patients with a lower exercise tolerance or with a higher rate-pressure product at rest and at ischemic threshold. None of the characteristics of anginal symptoms or exercise test results predicted a greater efficacy of nifedipine over metoprolol.

Conclusions. The results of a baseline exercise test, but not the characteristics of anginal symptoms, may offer useful information for selecting medical treatment in stable angina pectoris.     

Negative selection of peripheral blood stem cells to support a tandem autologous transplantation programme in multiple myeloma

We recently described a two-step negative selection procedure whereby peripheral blood stem cells (PBSCs) were efficiently purged of contaminating neoplastic cells by a combination of monoclonal antibodies. Here, we report 60 newly diagnosed multiple myeloma (MM) patients treated with a double transplant programme and randomized to receive either unmanipulated or in vitro purged PBSCs. We demonstrated that this technique is feasible and safe without significant loss of either CD34+ or CD3+ cells. Haematological engraftment and immunological reconstitution were rapid without treatment-related mortality. Using polymerase chain reaction (PCR), we compared the level of minimal residual disease (MRD) in PBSC before and after in vitro purging and in vivo after transplant. A median of one tumour cell per 10(2) normal cells (range 10(1)-10(5)) was seen in the unmanipulated aphereses with a 3-4 log reduction after manipulation in vitro. However, despite this tumour debulking, all patients remained PCR positive in vivo. At 3 years, the estimated event-free survival was 40% in the control arm and 72% in the experimental arm (P = 0.05), whereas the estimated overall survival was 83% in both arms. This suggests that autologous transplantation using efficiently purged PBSCs can be performed safely, but confirms the need for innovative protocols for MRD eradication in vivo.     

Effectiveness of adjunctive stent implantation following directional coronary atherectomy for treatment of left anterior descending ostial stenosis

The aim of this study was to evaluate the acute and long-term angiographic and clinical results of optimal plaque debulking by means of directional coronary atherectomy (DCA) followed by stent implantation for treatment of left anterior descending (LAD) ostial stenosis. Eighty consecutive patients (66 men; aged 57 +/- 10 years) with angina pectoris, documented anterior myocardial ischemia, and de novo LAD ostial stenosis prospectively underwent DCA and stent deployment. They were evaluated angiographically after 6 months and clinically for up to 30 +/- 29 months. The primary success rate was 98%. The in-hospital complications were 1 death due to in-stent subacute thrombosis 7 days after the procedure, 1 non-Q-wave myocardial infarction, and 1 retrograde left main artery dissection. The angiographic binary restenosis rate was 14.5%, and the loss index was 0.38 +/- 0.35. The target lesion revascularization (TLR) rates at 6, 12, and 24 months were 6.0%, 14.5%, and 16.3%, respectively, and the combined event rates (death, nonfatal myocardial infarction, TLR) at the same times were 8.7%, 17.5%, and 21.2%, respectively. These results indicate that the combined approach of DCA and stent implantation is feasible and safe in patients with LAD ostial lesions, has a high success rate, a low incidence of restenosis, and a good long-term outcome.     

Detection of treatable neonatal liver disease by expanded newborn screening

Two neonates were identified at age 48 h by expanded newborn screening, with abnormal methionine and tyrosine concentrations, which were confirmed on repeat samples. Evidence of previously unsuspected liver disease was found at recall, and there was radiological and biochemical evidence of severe liver disease with hepatic synthetic failure. After inborn errors of metabolism (IEMs) were excluded, both were considered to have neonatal haemochromatosis, on the basis of raised ferritin, iron saturation, and very high α-fetoprotein and confirmed by a mildly hyperferritinaemic sibling in the first case, and raised ferritin and iron saturation in the second. However, it was not feasible to obtain tissue confirmation as the requirement for early therapy precluded biopsy. The babies were treated with antioxidants and iron-chelating agents, and the coagulopathy and hypoalbuminaemia were corrected. Both made a complete recovery and remain well after follow-up. Newborn screening programmes could consider advising clinicians, when tyrosine and methionine values are elevated, that once IEMs are excluded liver disease from other causes must be sought. Neonatal haemochromatosis is an example of one such disease that is potentially treatable.     

Preserved Dendritic Cell HLA-DR Expression and Reduced Regulatory T Cell Activation in Asymptomatic Plasmodium falciparum and P. vivax Infection

Clinical illness with Plasmodium falciparum or Plasmodium vivax compromises the function of dendritic cells (DC) and expands regulatory T (Treg) cells. Individuals with asymptomatic parasitemia have clinical immunity, restricting parasite expansion and preventing clinical disease. The role of DC and Treg cells during asymptomatic Plasmodium infection is unclear. During a cross-sectional household survey in Papua, Indonesia, we examined the number and activation of blood plasmacytoid DC (pDC), CD141⁺, and CD1c⁺ myeloid DC (mDC) subsets and Treg cells using flow cytometry in 168 afebrile children (of whom 15 had P. falciparum and 36 had P. vivax infections) and 162 afebrile adults (of whom 20 had P. falciparum and 20 had P. vivax infections), alongside samples from 16 patients hospitalized with uncomplicated malaria. Unlike DC from malaria patients, DC from children and adults with asymptomatic, microscopy-positive P. vivax or P. falciparum infection increased or retained HLA-DR expression. Treg cells in asymptomatic adults and children exhibited reduced activation, suggesting increased immune responsiveness. The pDC and mDC subsets varied according to clinical immunity (asymptomatic or symptomatic Plasmodium infection) and, in asymptomatic infection, according to host age and parasite species. In conclusion, active control of asymptomatic infection was associated with and likely contingent upon functional DC and reduced Treg cell activation.     

Comparison of two mood induction procedures

A total of 162 college students participated in an experiment designed to compare the strength and durability of two laboratory-based mood induction procedures (MIPs). Subjects were randomly assigned either to the Velten positive, negative, or neutral self-statement MIP or to a manipulated success, failure, or control condition on an ostensible achievement task. Mood was measured prior to, immediately after, and at five 6-minute intervals following exposure to the MIPs. Results indicated that both MIPs were effective in influencing mood in intended directions. However, the Velten procedure induced greater initial but more transient depressed affect than manipulated failure. The MIPs were essentially equivalent in generating brief increases in positive mood. An ethical question was raised by the durability of negative affect induced by the failure manipulation.The authors wish to thank three anonymous reviewers for their helpful comments on an earlier draft of this article.     

Overview of ventilator-induced lung injury mechanisms

PURPOSE OF REVIEW: Mechanical ventilation is the main supportive therapy for patients with acute respiratory distress syndrome. As with any therapy, mechanical ventilation has side effects and may induce lung injury. This review will focus on stretch-dependent activation of alveolar epithelial and endothelial cells and polymorphonuclear leukocytes, and apoptosis/necrosis balance. RECENT FINDINGS: The past year has seen important research in the area of mechanotransduction and lung native immunity, suggesting further mechanisms of lung inflammation and injury in ventilator-induced lung injury. Research in the past year has also stressed the importance of inflammatory response by alveolar cells and role of polymorphonuclear leukocytes in stretch-induced lung injury and has suggested a role for apoptosis in the maintenance of the alveolar epithelium. SUMMARY: The proportion of patients receiving protective ventilatory strategies remains modest. If efforts to minimize the iatrogenic consequences of mechanical ventilation are to succeed, there must be a greater understanding of the signal transduction mechanisms and the development of potential pharmacologic targets to modulate the molecular and cellular effects of lung stretch.     

Tryptase-positive mast cells and angiogenesis in keloids: a new possible post-surgical target for prevention

Literature data indicate that mast cells (MCs) are involved in angiogenesis through the release of several pro-angiogenetic factors among which tryptase, a serine protease stored in MC granules, is one of the most active. However, no data are available concerning the role of MCs during keloids’ angiogenesis. In this study, we evaluated the correlations of the number of MCs positive to tryptase (MCDPT) and microvascular density (MVD) within a series of 15 keloids and 10 normotrophic scars, by means of immunohistochemistry and image analysis methods. Data demonstrated a significant difference of MVD and MCDPT between keloids and normotrophic scars and a significant correlation between MVD and MCDPT in keloids. Our results suggest that tryptase-positive MCs might play a key role in keloids’ angiogenesis. In this context, several tryptase inhibitors might be clinically evaluated as a possible new anti-angiogenetic approach to prevent keloid formation after surgery.