Uremic malnutrition: new insights into an old problem

Uremic malnutrition is highly prevalent and is associated with poor clinical outcomes in end-stage renal disease (ESRD) patients. Inadequate diet and a state of persistent catabolism play major roles in predisposing these patients to uremic malnutrition and appear to have an additive effect on overall outcome. Recent studies highlight the existence of a complex syndrome involving chronic inflammation, metabolic abnormalities, and hormonal derangements contributing to the increased morbidity and mortality observed in ESRD patients. Novel strategies such as appetite stimulants, anti-inflammatory drugs, and anabolic hormones along with conventional nutritional supplementation may provide potential interventions to improve clinical outcome in ESRD patients.     

Lead intoxication — new insights into an old problem

The epidemiology, clinical symptomatology, diagnosis and management of acute and chronic lead intoxication are reviewed. While acute lead intoxication has become rare, the elevated environmental lead burden is thought to play a causal role in hypertension. Lead may also be linked with neuropsychological disorders of children and possibly even chronic renal failure. The epidemiological and experimental evidence for this hypothesis is critically discussed.     

Whiplash injuries and associated disorders: new insights into an old problem

European Spine Journal -     

Ketamine: new uses for an old drug

Over the years, ketamine has found many applications in paediatric anaesthesiology. Recent insights into the mechanism of its central action, and the pharmacology of its isomers have led to a re-evaluation of this drug, expanding the range of indications in adults. The best examples of the uses of ketamine as an analgesic are: in brief diagnostic or therapeutic procedures, during the post-operative period in neonates and infants as well as in paediatric anaesthesia and intensive care.     

Ketamine: a new look at an old drug

Ketamine is a major drug for induction of patients with hypovolemia and for general anaesthesia under primitive conditions, but also has excellent properties for more generalized use in children, adults and other fragile patients. Potential beneficial effects on cardiac ischaemia and cerebral injury is presently explored, as well as the effects of ketamine as an potent analgesic drug. Combination with propofol or midazolam for sedation provides analgesia, sleep and spontaneous ventilation. The S-isomer of ketamine has a lower incidence of psychomimetic side effects in equianalgesic doses compared with the racemate or the R-isomer alone.     

硫酸镁:一种老药的新应用

背景 近几年,随着临床医学的飞速发展,药物应用的不断实践、探索和总结,硫酸镁在各个学科领域的应用越来越广泛. 目的 综述硫酸镁在临床中的新用途及对传统应用的新认识,为临床用药提供参考. 内容 介绍硫酸镁多种药理学作用在临床中的应用进展,进一步拓宽其应用领域. 趋向 使硫酸镁更加安全、有效、广泛地应用于临床.     

Ketamine: a new look to an old drug

Ketamine is an NMDA receptors antagonist, with a potent anaesthetic effect. NMDA receptors are involved in nociceptive modulation, in the wind-up phenomenon, in peripheral receptive fields expansion, in primary and secondary hyperalgesia, in neuronal plasticity. Ketamine effects are well-known: it produces a state of "dissociative anaesthesia", amnesia, and, at the same time, it mantains the respiratory drive effective and supports the sistemic arterial blood pressure. Anaesthesiologists are also familiar with its side-effects, like the increase of salivar and bronchial secretions, the possible increase of intracranial and pulmonary pressures and the dysphoric effect that may produce vivid and sometimes unpleasant dreams. Reviewing scientific data and studies about the use of ketamine in children, many considerations come out: at first they considered the effects of the racemic ketamine, then they evaluated the S-enantiomer. Many surveys studied the effects (analgesia, sedation, side-effects) of different doses or different routes of administration. Other studies were designed to compare ketamine to clonidine or opioids as adjuvants in paediatric regional anaesthesia with local anesthetic drugs, in order to prolong analgesia. In our Children's Hospital, we use ketamine in the operating room, in intensive care unit and for any procedure in hospital wards. The suggested doses are: Epidural or caudal route (as an ajuvant for local anaesthetic agents, in the treatment of postoperative pain): 0.5 mg/kg. Sedative/analgesic effect (for algesic procedures): 1-2 mg/kg i.v. Continuous infusion (intensive care unit): 0.5 mg/kg/h, with a range from 20-30 microg/kg/min to 80 microg/kg/min, depending on the age of the patient.     

Male sex determination: insights into molecular mechanisms

Disorders of sex development often arise from anomalies in the molecular or cellular networks that guide the differentiation of the embryonic gonad into either a testis or an ovary, two functionally distinct organs. The activation of the Y-linked gene Sry (sex-determining region Y) and its downstream target Sox9 (Sry box-containing gene 9) triggers testis differentiation by stimulating the differentiation of Sertoli cells, which then direct testis morphogenesis. Once engaged, a genetic pathway promotes the testis development while actively suppressing genes involved in ovarian development. This review focuses on the events of testis determination and the struggle to maintain male fate in the face of antagonistic pressure from the underlying female programme.     

Metabolomics insights into pathophysiological mechanisms of nephrology

Kidney diseases (KD), a major public health problem that affects about 10 % of the general population, manifest in progressive loss of renal function, which ultimately leads to complete kidney failure. However, current approaches based on renal histopathological results and clinical parameters lack sensitivity and are not sufficient to characterize the category and progression of nephrology or to predict nephrology progression risk reliably or to guide preventive interventions. The high incidence and financial burden of KD make it imperative to diagnose KD at early stages when therapeutic interventions are far more effective. Nowadays, the appearance of metabolomics (the high-throughput measurement and analysis of metabolites) has provided the framework for a comprehensive analysis of KD and serves as a starting point for generating novel molecular diagnostic tools for use in nephrology. Changes in the concentration profiles of a number of small-molecule metabolites found in either blood or urine can be used to localize kidney damage or assess kidneys suffering from injury. The power of metabolomics allows unparalleled opportunity to query the molecular mechanisms of KD. Novel metabolomics technologies have the ability to provide a deeper understanding of the disease beyond classical histopathology, redefine the characteristics of the disease state, and identify novel approaches to reduce renal failure. This review gives an overview of its application to important areas in clinical nephrology, with a particular focus on biomarker discovery. Great strides forward are being made in breaking down important barriers to the successful prevention and treatment of this devastating disorder.     

Depressant effects of volatile anesthetics upon rat and amphibian ventricular myocardium: insights into anesthetic mechanisms of action

To clarify the mechanisms by which volatile anesthetics may depress myocardial contractility, the depressant effects of equivalent concentrations of isoflurane, enflurane and halothane were compared in rat and frog ventricular myocardium, preparations which differ markedly in excitation-contraction coupling. In Tyrode solution, right ventricular papillary muscles from rat exhibited very large, rapidly developing contractions after rest, with a subsequent negative force-frequency relation as the stimulation rate was increased to 0.1, 0.25, 0.5, 1, 2, and 3 Hz. The large contractions after rest and at 0.1 Hz were depressed by 0.75% halothane and 1.7% enflurane to about 60% of control, but less so by 1.3% isoflurane (approximately 0.8 MAC). Halothane at 1.5% was more depressant than 2.5% isoflurane at all stimulation rates, while 3.5% enflurane caused intermediate depression (approximately 1.6 MAC). Contractions in frog ventricular strips were studied in Ringer solution following rest and at stimulation rates of 0.1, 0.25, 0.5, and 1 Hz, in the absence and presence of equivalent anesthetic concentrations. At 0.1 to 1 Hz, isoflurane was less depressant than equivalent concentrations of halothane. Enflurane (1.7%) was less depressant than 0.75% halothane at 0.1 and 0.25 Hz; 3.5% enflurane was more depressant than 2.5% isoflurane at 1 Hz. Anesthetic effects on sustained contractures were also studied in frog ventricular strips that were superfused for 4-5 min with 40, 60, 80, and 100 mM K Ringer solution. Contractures induced by 80 and 100 mM K solution were depressed more by halothane (to 60% of control) than by isoflurane or enflurane (approximately 85% of control). However, only enflurane depressed the contractions at 1 Hz more than the sustained contractures in 100 mM K Ringer. The Ca2+ for activating contractions in rat ventricle is derived largely from the sarcoplasmic reticulum, the intracellular Ca2+ accumulation and release organelle. In contrast, Ca2+ for activating contractions in the frog ventricle originates primarily from the external medium. These results suggest that halothane is more potent than isoflurane in reducing the amount of Ca2+ rapidly released from the sarcoplasmic reticulum (as observed in rat), as well as in depressing entry of extracellular Ca2+ to activate myofibrils (as in frog). Enflurane appears to have intermediate potency with actions distinct from halothane and isoflurane. The greater potency of halothane may also be due in part to greater direct depression of actin-myosin ATPase.     

Vascular calcifications in uremia: old concepts and new insights

The annual mortality rate in uremic patients, corrected for age, sex, and race, is significantly higher than in the general population. This is primarily due to cardiovascular events. Vascular calcifications play a vital role in the development of cardiovascular morbidity and subsequent increased mortality. Vascular calcification affects both vascular intima and media layers and its mechanism remains poorly understood. Over the last few years it has been shown that, in addition to traditional cardiovascular risk factors, disturbances in mineral metabolism in the uremic milieu, calcium-containing phosphate binders, and vitamin D treatment of secondary hyperparathyroidism may contribute to the pathogenesis of vascular calcifications. Other uremia-related risk factors (e.g.increased oxidized low-density lipoprotein cholesterol, uremic toxins, increased oxidative stress, dialysis and dialysate-related factors, hemodynamic overload, hyperhomocysteinemia) may also play a role. In uremic patients, apart from these facilitating factors, decreased levels of endogenous calcification inhibitors such as fetuin-Amatrix Gla protein, osteoprotegerin, and osteopontin have also been associated with increased calcium-phosphate precipitation in extraskeletal tissues. Finally, vascular calcification is the outcome of the active and dynamic balance of procalcifying and anticalcifying influences. For the prevention and treatment of vascular calcifications, it is essential to avoid treatment modalities that lead to calcium overload, achieve good metabolic control, and optimize dialysis.     

The pathogenesis of ANCA-associated vasculitides: old hypotheses and new insights

The pathomechanism of the ANCA-associated vasculitides is discussed in light of the abstracts presented at the ANCA- and Vasculitis Workshop 2005 in Heidelberg!