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Gadolinium-based contrast agents can be used in diagnostic and interventional angiography, and are safe in recommended doses in patients with impaired renal function, but the image quality is usually unsatisfactory. The objective of the present study is to evaluate the safety of gadolinium mixed with a small quantity of iodine-based contrast agent and the image quality of this mixture in patients with renal insufficiency undergoing diagnostic coronary angiography. Forty-two patients with baseline creatinine level>1.5 mg/dl were randomized into gadolinium or iodine groups. In the gadolinium group gadodiamide was mixed with 1:3 iohexole and in the iodine group only this agent was used as contrast material. Peak creatinine levels 48-72 h after the procedure were measured. The primary end point was the development of contrast-induced nephropathy (CIN), defined as >25% increase of baseline creatinine levels, and the secondary end points were absolute and relative changes in baseline creatinine levels. Total contrast volumes used were not different between groups (57+/-11 ml in gadolinium and 55+/-10 ml in iodine; P=0.68). Mean creatinine level did not increase significantly in the gadolinium group (from 1.9+/-0.3 to 1.9+/-0.4 mg/dl; P=0.06), but did in the iodine group (from 2.0+/-0.4 to 2.3+/-0.5 mg/dl; P=0.001). No patient had CIN in the gadolinium group whereas 5 (23%) patients had this phenomenon in the iodine group (P=0.048). Contrast regimen was very well tolerated in the gadolinium group, with only transient headache in two patients. Gadodiamide mixed with a small quantity of iohexol is safe in patients with azotemia undergoing diagnostic coronary angiography. The image qualities obtained with this combination are also satisfactory in all of the cases. Further evaluation of the safety of this technique is warranted, especially in other types of diagnostic and interventional procedures in which a higher amount of contrast dye is needed.
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PMID:Safety of gadodiamide mixed with a small quantity of iohexol in patients with impaired renal function undergoing coronary angiography. 1753 28

Haemolytic-uraemic syndrome (HUS) is a rare cause of insulin-dependent diabetes mellitus during the acute stage. We previously reported the case of a 3-year-old girl having presented with typical HUS with diarrhea, microangiopathic anaemia, thrombocytopenia and acute renal failure (17 days of anuria). Transient hyperglycaemia (highest level: 513 mg/dl) was observed, requiring continuous intravenous insulin infusion for 9 days. Subcutaneous insulin injections were stopped after 24 days. Oral glucose tolerance test performed 4 months after normalization of blood glucose was normal. HLA DQ genotype (DQA1-DQB1.AZH/DQA3-DQB3.1) was not at risk for type 1 diabetes and there were no auto-antibodies (ICA and IAA). The 3-years follow-up was marked by persistent arterial hypertension, proteinuria and slight renal insufficiency despite angiotensin-converting enzyme inhibitor treatment. Ten years after HUS occurred (the patient had been lost to follow-up for 7 years), she came back with complaints of headache but neither polyurodipsia nor weight loss. She was found to have arterial hypertension. Chronic renal impairment had moderately progressed with decreased glomerular filtration rate (63 ml/min/1.73 m2) and proteinuria (2 g/24 hours). Fasting blood glucose was 189 mg/dl and reached 315 mg/dl during an oral glucose tolerance test. HbA1c level was 8.2% (N<6.2%) and diabetes mellitus was diagnosed without any signs of autoimmunity (IAA, ICA, GADA and IA2B were negative). Good glycaemic control was obtained with 0.5 U/kg/day of insulin. In conclusion, transient beta-cell dysfunction complicating HUS acute stage may evolve to overt non-autoimmune diabetes mellitus (microangiopathic process?), even after a long free interval. This case emphasizes the need for a long-term follow-up of patients with HUS.
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PMID:Insulin-dependent diabetes mellitus as long term complication of haemolytic-uraemic syndrome. 1679 6

Therapy with intravenous immunoglobulins (IVIg) is considered to be a safe treatment for a number of immune-mediated neurological diseases. Published data about prevalence of adverse effects range from 11 to 81%. The purpose of our study was to preserve a representative view on adverse effects by analysis of a large cohort of patients treated by IVIg. A recent prospective study reported 42.7% adverse events. The majority of patients presented with minor adverse effects, mostly asymptomatic laboratory changes. Rash or mild headache occurred especially when IVIg was administered with an infusion flow higher than 10 g/h. Severe complications like deep vein thrombosis or others are rare. In addition to its efficacy, IVIg therapy appears to be a safe therapy in immune-mediated neurological diseases. Most patients show no or minor adverse effects. Patients with pre-existent disorders like heart or renal insufficiency or immobilized patients, however, may be at higher risk for complications.
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PMID:Adverse effects of treatment with intravenous immunoglobulins for neurological diseases. 1699 59

All children aged > or = 3 years should have an annual blood pressure (BP) measurement taken during a routine physical examination. Physicians should become familiar with recommended pediatric normative BP tables. BP above the 95th percentile may require drug therapy. There are several categories of antihypertensives available to the clinician. Calcium channel antagonists (CCAs) are a class of drugs that exert their antihypertensive effect by inhibiting the influx of calcium ions across the cell membranes. This results in dilatation of peripheral arterioles. When given orally, CCAs are metabolised in the liver by cytochrome P450 (CYP) enzyme CYP3A4; hence, some CCAs will affect the half-life of drugs that share this enzyme system for their metabolism. CCAs can be safely used in children with renal insufficiency or failure and as a general rule there is no need to modify drug dosage in this population. CCAs are generally well tolerated; most adverse effects appear to be dose related. Headache, flushing, gastrointestinal upset, and edema of the lower extremities are the most common symptoms reported with the use of CCAs. Pediatric data regarding safety and efficacy of CCAs have mostly been obtained from retrospective analyses. Extended-release nifedipine and amlodipine are the two most commonly used oral CCAs in the management of pediatric hypertension. These drugs can be given once a day, although many children require twice-daily administration. Extended-release nifedipine has to be swallowed whole; hence, its use in younger children who cannot swallow pills is limited. Amlodipine can be made into a solution without compromising its long duration of action; therefore, it is the CCA of choice for very young children. Oral short-acting nifedipine and intravenous nicardipine are safe and effective CCAs for the management of hypertensive crisis in children. Short-acting nifedipine can cause unpredictable changes in BP; hence, it should be used cautiously and in low doses. Intravenous nicardipine has a rapid onset of action and a short half-life. Intravenous infusion of nicardipine can be titrated for effective control of BP. Intravenous nicardipine has been used safely in hospitalized children and newborns for the management of hypertensive crisis, and for controlled hypotension during surgery. CCAs are a class of antihypertensives that are safe and effective in pediatric patients. They have relatively few adverse effects and are well tolerated by children. This article reviews CCAs as antihypertensives in the management of pediatric hypertension.
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PMID:A review of calcium channel antagonists in the treatment of pediatric hypertension. 1715 43

A 36-year-old woman, who had given birth once before, had an eclamptic epileptic seizure eight days after caesarean delivery of healthy premature twins. Severe headache and loss of vision, leading to blindness, had not been recognised as prodromal signs by the healthcare professionals involved. Thereafter, she suffered a generalised epileptic seizure with tongue bite. She recovered fully after treatment with magnesium sulphate and nifedipine. Eclampsia is a severe condition with high rates of maternal complications, such as abruptio placentae, disseminated intravascular coagulation, neurological problems, pulmonary oedema, acute renal insufficiency and even death. Recognition of prodromal symptoms like headache, visual disturbances and upper abdominal pain is of the utmost importance. Magnesium sulphate intravenously is the treatment of choice. About 25% of the cases of postpartum eclampsia develop 2-28 days after delivery. A history of pre-eclampsia before or during the delivery is often absent. There is a relative increase in the incidence of late postpartum eclampsia, possibly because of misinterpretation ofprodromal symptoms, as illustrated by this case report. Every physician should be able to recognise the symptoms of pre-eclampsia and be aware of the possible consequences.
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PMID:[Late postpartum eclampsia]. 1750 Mar 49

A new hepatitis B vaccine (FENDrix, GlaxoSmithKline Biologicals) containing as active substance 20 microg of recombinant hepatitis B virus surface antigen produced in Saccharomyces cerevisiae has recently been licensed in Europe. It is prepared with a novel adjuvant system: aluminum phosphate and 3-O-desacyl-4 -monophosphoryl lipid A. It is intended for use in adults from the age of 15 years onwards for active immunization against hepatitis B virus infection for patients with renal insufficiency (including prehemodialysis and hemodialysis patients). It is applied in a four-dose scheme: day 0, month 1, 2 and 6 after day 0. Due to the improved adjuvant system it induces higher antibody concentrations that reach protective levels in a faster fashion. Furthermore, due to higher titers reached after the primary immunization course, protective levels are retained for a longer period of time. Vaccination with FENDrix induces more transient local symptoms, with pain at the injection site being the most frequently reported solicited local symptom. Other symptoms such as fatigue, gastrointestinal disorders and headaches were also frequently observed but resolved without sequelae. The higher risk of hepatitis B transmission in patients with end-stage renal disease and the often immunocompromised status of these patients afford a tailored vaccination strategy that, up to now, has consisted of injecting double doses of ordinary hepatitis B vaccines. With the introduction of FENDrix there now exists an efficient alternative with superior immunogenicity that is, despite comparatively higher reactogenicity, well tolerated.
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PMID:New hepatitis B vaccine formulated with an improved adjuvant system. 1740 63

Most patients with acute heart failure present with increased left ventricular filling pressure and high or normal blood pressure; only a minority present with cardiogenic shock. In this context, therapy with vasodilators in the acute setting can improve both hemodynamics and symptoms. Vasodilators are usually given in conjunction with diuretics, although much of the acute effect of loop diuretics may be due to venodilation. Currently available agents include nitroglycerin, nitroprusside, and nesiritide. Nitroglycerin relieves pulmonary congestion primarily through direct venodilation, but may dilate coronary arteries and increase collateral blood flow at higher doses, an effect desirable in patients with ischemia. Tachyphylaxis may develop, necessitating incremental dosing. The major adverse effects of nitrates are hypotension and headache. Nitroprusside is a balanced arterial and venous vasodilator with a very short half-life, facilitating rapid titration. Afterload reduction lowers blood pressure and can increase stroke volume. The major complications of nitroprusside therapy are hypotension, and toxicity from accumulation of cyanide or thiocyanate, usually in patients with renal insufficiency treated for more than 24 h. Nesiritide, a recombinant form of human B-type natriuretic peptide (BNP), is a venous and arterial vasodilator that may also potentiate the effect of concomitant diuretics. Hypotension is the most common side effect. In addition, meta-analyses have suggested that nesiritide may worsen renal function and decrease survival at 30 days compared to conventional therapies. Resolution of these concerns awaits completion of appropriately powered prospective clinical trials. Angiotensin-converting enzyme (ACE) inhibitors have vasodilatory effects, but intravenous infusion of enalapril within 24 h of ischemic chest pain is not recommended. Oral ACE inhibition may be used to reduce afterload in other settings if blood pressure permits. Use of calcium antagonists in acute heart failure is not recommended.
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PMID:Vasodilators in acute heart failure. 1744 37

Dalbavancin is a second-generation lipoglycopeptide bactericidal agent. Due to its once-weekly intravenous (i.v.) dosing and greater tissue penetration, dalbavancin may offer advantages in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) as compared to vancomycin, the gold standard in the treatment of MRSA. Dalbavancin binds to the terminal D-alanyl-D-alanine moiety of peptidoglycan precursors in bacterial cell walls. Such binding blocks enzymes involved in the final stages of peptidoglycan synthesis and cell wall formation. Dalbavancin exhibits an elimination half-life of approximately 200 hours, allowing it to be dosed weekly. The best-studied dosing schedule for dalbavancin involves the i.v. administration of 1 g of dalbavancin followed by 500 mg one week later. Phase III clinical trials comprising more than 1,500 patients evaluated once-weekly dalbavancin in Gram-positive skin and soft tissue infections (SSTIs). When compared to linezolid, cefazolin or vancomycin, dalbavancin met the primary endpoint of noninferiority at two weeks following therapy. The side-effect profile of dalbavancin is mild, with headache and pyrexia being the most common adverse effects. Dalbavancin is eliminated renally and hepatically, and does not need dose adjustments in patients with renal insufficiency. Once-weekly dosing with dalbavancin gives it another advantage when compared with vancomycin, and may alleviate the need for the continued presence of indwelling catheters in some patients with SSTIs and other infections requiring prolonged doses of antibiotics. While some in vitro evidence supports dalbavancin's effectiveness against vancomycin-resistant S. aureus, the preponderance of in vivo evidence does not demonstrate its effectiveness against vancomycin-resistant S. aureus.
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PMID:Dalbavancin: a review. 1772 97

We report on a 12-year-old female patient with steroid-dependent nephrotic syndrome due to focal segmental glomerulosclerosis (FSGS) since her 3rd year of life. She was twice treated with oral cyclophosphamide and received antihypertensive treatment with atenolol and enalapril. After 3 years without any control or therapy, she presented in a reduced general condition with hypertensive crisis and a blood pressure of 220/130 mmHg, headache, vomiting and loss of vision. Additionally, renal insufficiency (creatinine 11.4 mg/dl, urea 157 mg/dl), with oliguria, anaemia and a severe relapse of nephrotic syndrome, was present. Initial treatment with steroids, albumin-furosemide infusions and antihypertensive drugs was unsuccessful, and dialysis treatment was necessary. Renal biopsy showed an advanced stage of the known FSGS and, surprisingly, a thrombotic microangiopathy. Further diagnostic investigations revealed no signs of haemolytic-uraemic syndrome, but echocardiography showed left ventricular hypertrophy, and hypertensive retinopathy grade 3 was diagnosed, making severe hypertension the most likely reason for the thrombotic microangiopathy. While adequate antihypertensive treatment led to regress of left ventricular hypertrophy and hypertensive retinopathy, renal function did not recover, and the patient remained dialysis-dependent. In conclusion, severe hypertension in chronic kidney disease can lead to target organ damage and thrombotic microangiopathy, which may further worsen renal function.
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PMID:Thrombotic microangiopathy as a complication in a patient with focal segmental glomerulosclerosis. 1788 57

The number of dopamine agonists (DA) used in Parkinson's disease (PD) is gradually increasing. They have different affinity to the dopamine receptor subtypes. When choosing one of these drugs one should consider its efficacy in monotherapy in early phase and in combined therapy with levodopa in advanced PD, side effects profile, effectiveness in non-motor symptoms of PD, dosing and route of administration. The efficacy of new DA (pramipexol, ropinirol, cabergoline) is probably higher than bromocriptine and comparable to pergolide with similar profile of the most common side effects (headache, vertigo, nausea, somnolence, oedema). However, fibrosis of the pleura, peritoneum and pericardium as well as valvular heart disease (caused by noninflammatory fibrotic degeneration) are significantly more common after ergoline DA (pergolide, cabergoline). Pramipexol shows antidepressant activity. Ropinirol is metabolised by the liver and can be safely administered in renal insufficiency. Pramipexol is excreted in urine and the risk of interaction with other drugs metabolised in the liver is reduced. Rotigotine is the only DA available as skin patches. Whenever necessary, one DA agent can be changed safely overnight to another one.
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PMID:[Choosing a dopamine agonist in Parkinson's disease]. 1794 54


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