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Despite all the knowledge, the cellular and molecular mechanisms involved in myeloproliferative neoplasm (MPN) pathophysiology remain unclear. Authors have shown galectin-1 (Gal-1) and 3 playing roles in tumour angiogenesis and fibrosis, which were correlated with poor prognosis in patients with MPN. In the present study LGALS1 and LGALS3 were differently expressed between polycythemia vera, essential thrombocythemia (ET) and primary myelofibrosis (PMF) diseases. Increased LGALS3 expression was associated with a negative JAK2 V617F status mutation in leucocytes from PMF but not in patients with ET without this mutation. However, a positive Janus kinase 2 (JAK2) V617F cell line established from patients with ET (SET-2 cells) when treated with JAK inhibitor presented high levels of LGALS3. Additionally, high LGALS1 expression was found in CD34(+) cells but not in leucocytes from patients with PMF, in absence of JAK2 V617F mutation, and also in SET-2 cells treated with JAK inhibitor. Thus, our findings indicate that differential expression of LGALS1 and/or LGALS3 in patients with MPN is linked with JAK2 V617F status mutation in these diseases and state of cell differentiation.

Objective Dopamine is a neurotransmitter that mediates the reward value of food. Methylphenidate (MPH) selectively binds and inhibits the dopamine transporter, thus increasing brain dopamine levels shortly after oral administration. This investigation studied whether a single dose of MPH decreases energy intake (EI) in obese teenagers compared to placebo (P). Methods This study used a single-blind, placebo-controlled, within subject design. Teenagers with body mass index (BMI) ≥95th percentile underwent two identical meal tests (P or MPH) after a 10 h fast in random order. Food was weighed before and after the meals, and EI was calculated as energy content/gram of consumed foods. Total and macronutrient EI (mean ± SD) were analyzed by Mann–Whitney U and Wilcoxon tests. Results Twenty-two subjects (15 females, 7 males) completed the study. Participants were 13.4 ± 2.2 years old and had BMI 34.9 ± 10.7 kg/m². EI from fat (167 vs. 203 kcal, P = 0.03) and carbohydrates (311 vs. 389 kcal, P = 0.04) was decreased for MPH compared to P meals, with a trend in decreased total EI (545 vs. 663 kcal, P = 0.06). Conclusion A single dose of MPH decreases EI from fat and carbohydrates in obese adolescents. This effect underscores the importance of central dopamine signaling on eating behavior.

We describe a case of genetic Creutzfeldt-Jakob disease (CJD) with deafness at the onset. We report clinical features, 14-3-3 protein positivity, electroencephalography and brain stem auditory evoked potential abnormalities, and high signal on magnetic resonance imaging in basal ganglia and temporal cortex. Similarities with CJD Heidenhain variant are discussed.

The hypothesis of the prenatal programming of adult diseases took on increasing interest from the moment that, in the 60s, an epidemiological association was proposed between low birth weight and cardiovascular diseases. In the last 20 years it has been demonstrated that individuals with low weight, low stature and thinness at birth have a higher risk of developing cardiovascular diseases and type 2 diabetes. Animal and clinical studies are casting light on the biological mechanisms underlying the association between modified development in the uterus and diseases, and on how growth in adolescence and in adult life can modulate this initial proneness to disease. One of the mechanisms that has aroused most interest among researchers is the reduced number of nephrons, associated with low birth weight, which predisposes to glomerulosclerosis and increased systemic arterial pressure in adult life. A correlation has also been found between low weight at birth and peripheral resistance to insulin. Nevertheless, it is thought that modified prenatal development is only a predisposing factor, open to profound influences in the course of postnatal development. It has in fact been demonstrated that accelerated development in the period of infancy and adolescence can extend the initial condition of neonatal suffering. Indirectly these studies renew and at the same time extend the concept of prevention, a priority aim of the physician of the third millennium.

Aims The aim of this case–control study was to compare quality of life (QoL) and treatment satisfaction in adults with Type 1 diabetes (T1DM) treated with either continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). Methods Consecutive patients aged between 18 and 55 years, and attending diabetes clinics for a routine visit, completed the Diabetes-Specific Quality-of-Life Scale (DSQOLS), the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and the SF-36 Health Survey (SF-36). Case (CSII) and control subjects (MDI) were recruited in a 1 : 2 ratio. Results Overall, 1341 individuals were enrolled by 62 diabetes clinics; 481 were cases and 860 control subjects. Cases had a longer diabetes duration and were more likely to have eye and renal complications. Age, school education, occupation and HbA 1c were similar. Of control subjects, 90% followed glargine-based MDI regimens and 10% used NPH-based MDI regimens. On multivariate analysis, after adjusting for socioeconomic and clinical characteristics, scores in the following areas of the DSQOLS were higher in cases than control subjects: diet restrictions ( β = 5.96; P < 0.0001), daily hassles ( β = 3.57; P = 0.01) and fears about hypoglycaemia ( β = 3.88; P = 0.006). Treatment with CSII was also associated with a markedly higher DTSQ score ( β = 4.13; P < 0.0001) compared with MDI. Results were similar when CSII was compared separately with glargine- or NPH-based MDI regimens. Conclusions This large, non-randomized, case–control study suggests quality of life gains deriving from greater lifestyle flexibility, less fear of hypoglycaemia, and higher treatment satisfaction, when CSII is compared with either glargine-based or NPH-based MDI regimens. Diabet. Med. 25, 213–220 (2008)

A functionally solitary kidney may be the consequence of renal agenesis, dysplasia, or surgical procedures. Compensatory hypertrophy and physiologic mechanisms intervene to preserve renal function. The authors discuss the physiopathology of solitary kidney in several clinical conditions.

Drug-related problems are associated with significant morbidity and mortality. Numerous factors contribute to the development of drug-related problems. These factors may be patient-dependent, such as the patient's degree of organ function and/or dysfunction, and underlying disease states. On the contrary the factors may depend on the specific drug and its pharmacokinetic parameters. Recently it has been also demonstrated the importance of genetic factors. Drug-related problems include a wide range of situations including the so-called drug misadventuring: adverse drug reaction (ADR), adverse drug event (ADE), drug-induced disorder (DID), adverse drug experience (ADEexp). Certain drug classes are commonly associated with drug-induced disorders. Antibiotics and chemotherapeutic agents are responsible for approximately 30 percent of all adverse reactions. By an epidemiologic point of view between 3% and 11% of hospital admissions could be attributed to drug-related problems. Drug-induced disorders have historically been classified as predictable (Type A) or unpredictable (Type B) toxicity. Thus, a substantial portion of drug-induced disorders are predictable and potentially avoidable The kidney is vulnerable to drugs because of its high blood flow and large capillary surface area, its role as the excretory route for many drugs and its detoxifying action. Drug-induced acute renal failure accounts for 20% of total cases of acute renal failure in adult patients. Little is known about epidemiology of drug-induced disorders, especially in the pediatric kidney. Systematic epidemiological data on the incidence of drug-induced acute renal failure in newborn are not available. However, an increase in the last 10 years, in the involvement of drugs in acute renal failure has been observed in newborns. In the past it was suggested that drug-induced kidney damage (especially tht caused by aminoglycosides or glycopeptides) is less frequent and severe in newborns than in adults. However, this subject is controversial. Furthermore, it has recently been confirmed that low birth weights contribute to early onset of end stage renal disease. In view of the extremely widespread use of drugs in neonatology and the multiplicity of potential nephrotoxic factors, it is important to prevent iatrogenic effects. Ten rules for prevention of drug-induced nephrotoxicity are presented.

Hospital-acquired infection (nosocomial infection) is a world-wide problem. The peculiar susceptibility of newborns and children, the widespread use of antibiotics, advances in hospital practice, have resulted in an increased incidence and recognition of neonatal and pediatric bacterial nosocomial infections. The aim of this review is to present an update on epidemiology of hospital-acquired infections, quoting recent and relevant papers on this topic. Main risk factors for the neonatal and the pediatric intensive care infections are presented, respectively. Emerging antibiotic-resistant gram-positive and gram-negative bacteria in intensive care units are also considered. Infection control programmes are necessary to monitor and to prevent nosocomial infections.

The renal excretion of a drug can essentially be divided schematically into three functional processes: glomerular filtration, tubular reabsorption and tubular secretion. When assessing nephrotoxicity, the tubular secretion system, which allows transport of the drug from the blood to the urine via the tubular cells, is particularly important. Historically, two distinct tubular secretion mechanisms have been described for drugs: one via organic cations and the other via organic anions. More recently, a third tubular secretion mechanism has been identified, mediated by P-glycoprotein. In the present review, a number of examples will be given relating to antibiotic-induced kidney damage determined via the tubular reabsorption mechanism (aminoglycosides, amphotericin B) and via the tubular secretion mechanism (cephalosporins, vancomycin), respectively. Drug transport within the tubular cells is the first fundamental stage in the onset of the nephrotoxic process. Knowledge of these concepts is important for the prevention of iatrogenic kidney damage, particularly in patients with underlying disease receiving concomitant treatment with several potentially nephrotoxic molecules.

To review the accuracy of Leonardo's anatomical studies of the female external genitalia and the foetus, particularly those concerning the umbilical cord with its blood vessels.The anatomical drawings of Leonardo da Vinci which are now stored in the Windors Castle near London were reviewed and the accuracy of the details of the genital apparatus and foetus was evaluated. A written comment characterizes many of his drawings.He described accurately the position of the uterine blood vessels and the relationship between the pelvic organs. However his drawing and description of the female external genitalia and human placenta was incorrect because his understanding of it was inadequate. He believed that the human placenta had cotyledons like that of the ungulate uterus (drown side A of sheet 19). At the top of that sheet some Leonardo's details of the anatomic relationship are shown.In our opinion, Leonardo's misunderstanding is probably because he was only able to perform one anatomical dissection of a pregnant women and foetus and therefore his knowledge was limited. The resulting documentation of the pregnant women and foetus was therefore heavily supplemented with his enormous experience in animal anatomy.

Over the past thousands of years many examples can be found of the treatment given for asphyxia in the apparently dead subject. The resuscitation procedures were applied alike both in adults and in newborn babies. The first reference made to the mouth-to-mouth method was in the Kings'. In the second half of the 1800 many Authors proposed a method to resuscitate the asphyxiated newborn infant, which were still practiced up until the 1930 s. Many other different methods of air and 02 administration to the airway and stomach of an apparently dead newborn were well known and used in the 1800 s and still used in the 1950 s. Other methods used involved the dilatation of the rectum; the immersion in alternating warm and cold water and the use of a larynx tube developed by Chaussier which was then modified by other Authors. The use of tight fitting tracheal tubes and direct tracheal 02 administration after the clearing of the oropharynx using fingers and finally the mouth to mask and mouth to endotracheal tube breathing. All these examples are indicative of the approach taken in the resuscitation of the apparently dead infant. The science of resuscitation and its history continue to evolve....

Cefixime is a third-generation oral cephalosporin that is highly active against a broad range of gram-negative and some gram-positive aerobic bacteria. In non-complicated urinary tract infections it is at least as effective as other usual treatments, and has a low rate of side effects. Several clinical studies have been performed on cefixime in urinary tract infections both in adults and children. On the basis of the literature data, cefixime could be indicated in the treatment of non-complicated urinary tract infections in children either as monotherapy or as switch therapy.

Amphotericin B is the gold standard for antifungal treatment for the most severe mycoses. However, adverse effects are common, with nephrotoxicity being the most serious, occurring early in the course of treatment, and usually being reversible in most patients. Tubular damage is a well known problem associated with amphotericin B therapy but acute renal failure is the most serious complication. Recent studies have examined ways to ameliorate the well-known toxicities of amphotericin B. A new approach has been to complex the drug with lipids or entrap it in liposomes. This review will concern amphotericin B-induced nephrotoxicity, whose mechanisms are not completely clear. Nephrotoxicity seems related to direct amphotericin B action on the renal tubules as well as to drug-induced renal vasoconstriction. The main mechanisms of nephrotoxicity suggested in the literature are presented. The clinical picture at different ages (adults, children, newborns), interactions of clinical significance, strategies for prevention of amphotericin B-induced nephrotoxicity are summarized. To provide optimal patient care, it is imperative that the clinician understand the etiology of and the signs and symptoms associated with nephrotoxicity, as well as interventions to prevent nephrotoxicity in patients receiving amphotericin B.

The aim of this review is to describe the present status of prenatally diagnosed pyelectasis and hydronephrosis. Ultrasonographic definitions are presented, along with guidelines for the management of urinary tract dilatations. Isolated pyelectasis without caliceal involvement rarely constitutes a pathological situation and does not require any particular diagnostic or therapeutic measures. Obstructive dilatation is characterized by an obstacle to normal urinary flow situated at any level in the urinary tract, with consequent stagnation of urine and dilatation upstream of the obstruction. If the obstruction is not correctly treated it can cause a progressive deterioration of renal function. The presence of ureterectasia plays a crucial role in the diagnostic algorithm and a micturitional cystourethrography is necessary to look for a vesicoureteric reflux (VUR). The significance of urinary tract dilatation is discussed in detail.In newborns with pyelectasis or hydronephrosis the paediatrician's goal should be to strike the right balance between excessive medical intervention and sufficient intervention for the diagnosis of potentially dangerous conditions.

A review of significant studies published on vesicoureteric reflux (VUR) in children over the past two years is presented. Improvement in knowledge of genetic implications and pathogenetic mechanisms has been observed. Population at high risk of VUR is discussed in detail. VUR is unlikely to be a single nosological entity and it is possible to distinguish between two main clinical pictures. New instrumental and laboratory investigations are now available. Finally natural history of VUR and surgical treatment of VUR are briefly discussed.

OBJECTIVES To evaluate clinical and MRI effects of natural interferon beta treatment in both relapsing-remitting (RR) and secondary-progressive (SP) multiple sclerosis patients. MATERIAL AND METHODS A double-blind, randomized trial of natural interferon beta (nIFN-beta) in 58 ambulatory patients with RR and 40 with SP multiple sclerosis. Forty-nine patients (29 RR and 20 SP) were treated with intramuscular nIFN-beta6 MIU three times a week for 24 months and 49 control patients were treated with placebo. RESULTS Primary clinical endpoints were differences in exacerbation rates and proportion of patients remaining exacerbation-free. There were no significant baseline differences between the treated and placebo groups. In the treated RR group a significant reduction in exacerbation rate, an increase in the probability of remaining exacerbation-free, and an improvement in mean EDSS were found at 24 months. MRI activity and total lesion burden were significantly reduced in treated RR patients. In the SP group, nIFN-beta produced a significant reduction in EDSS score, a significant reduction in active lesion number, a marginally significant favourable difference in total lesion burden but no significant effect on the number of gadolinium-enhancing lesions. Side effects were transient and mild in treated patients. CONCLUSIONS These observations confirm that nIFN-beta is a promising and well-tolerated treatment for either RR or SP MS patients.

Hematuria is a common finding on a urinalysis, with a prevalence rate between 1% and 2%. The execution of screening of hematuria in children is controversial. Once hematuria has been identified, it is useful to identify sources of bleeding, as either glomerular or non-glomerular. If microscopic hematuria is confirmed, investigations would include: hypercalciuria screen, blood examinations (full blood count, renal function tests, complement and autoantibody screen), renal tract ultrasound, urinalysis of family members, audiogram, if family history of deafness is present, or family members present a positive dipstick. If all these tests are negative and microscopic hematuria persists, then a renal biopsy is advocated.

Urinary tract infections (UTIs) are not an uncommon event in the neonatal population. The reported incidence of UTIs in the newborns ranges from 0.1% to 5.5%, depending on the characteristics of the population studied and the diagnostic criteria used. A review of epidemiology, clinic, laboratory findings, imaging and therapy of neonatal UTIs is presented. Particular emphasis is given to the experience of the Italian Neonatal Nephrology Study Group.

Antibiotics are the leading cause of drug-induced kidney disease, and among them the aminoglycosides (AMG) are the main nephrotoxic agents, bringing about kidney damage via a direct dose-dependent mechanism. The combination of an aminoglycoside and a penicillin derivative is still the most commonly recommended and used first-line treatment modality in the empirical therapy of neonatal sepsis, despite the low therapeutic index of AMG. The immaturity of neonatal kidney function, particularly in preterm neonates, makes newborn infants particularly susceptible to AMG-induced kidney damage. Numerous factors intervene in bringing about AMG-induced kidney damage, such as factors related to the antibiotic itself (intrinsic toxicity, administration route, type of monitoring of blood concentrations), those related to the subject treated (neonatal age, constitutional sensitivity), and others related to associated pathology (neonatal anoxia, renal hypoperfusion, respiratory distress/mechanical ventilation, hyperbilirubinaemia/phototherapy, electrolyte disorders, and even the acute sepsis calling for antibiotic therapy), as well as pharmacological factors (concomitant therapies such as diuretics, indomethacin and other antibiotics, particularly glycopeptides and cephalosporins).

Using an electrode selective for the ion fluorine, it has been determined the amount of fluorine in samples of human milk. In a sample of 35 nursing mothers, only 10 have shown the required parameters. The amount of fluorine in the water all 35 mothers imbibed in their daily diet has been measured. The results showed a small amount of fluorine in human milk and a possible connection between the amount of fluorine in the mothers' daily diet and the amount of fluorine in human milk. From the results of the research it has been determined the necessity to give supplements of fluoride to nursing babies.

Introduction the early neonatal period is characterized by a rapid maturation of kidney function. Moreover, a variety of therapeutic interventions and the administration drugs may have harmful renal consequences. Goal We tested the hypothesis that drugs or therapeutics in the neonatal period could increase the risk for ARF in preterm newborns. Methods All preterm infants (261) with a G.A. 1.3 mg/dl or > 1 mg/dl respectively in subjects with a G.A. 33 weeks) and/or presence of oliguria. In neonates with impaired renal function, an important increase in Crs values was observed in all groups from the 3rd to the 10th day of life, with statistical significant differences among groups on day 7 (p=0.03) and day 10 (p=0.006). Then, values decreased but remained higher, compared to subject with normal renal function, in all neonates at 28th day of life. An inverse correlation is evident between G.A. And the percentage of neonates with impaired renal function (?2= 25.707, p

Postnatal changes in total hydroperoxides (TH) and advanced oxidation protein products (AOPP) in preterm newborns with and without hypoxia at birth

Urinary nitrite/nitrate concentrations are reasonable estimates of whole-body nitric oxide (NO) synthesis. L-arginine, the precursor of NO is present in fresh frozen plasma (FFP). Thus, we determined the effect of FFP on NO synthesis in 8 preterm infants (mean GA 33.1 ±2.2 w. range 30-37; BW 2050±350 g, range 1440-2710) admitted to NICU. No patient had perinatal asphyxia, respiratory disease, diarrhea, or conditions reported to alter urinary nitrite/nitrate concentrations. 5 newborns received FFP and 3 had aminoglycoside treatment for suspected but not confirmed infection. Daily 8-hour urine samples were collected during the first 5 days of life and kept at -20°C until the assay was performed. Nitrite/nitrate concentrations were measured spectrophotometrically using a modification of a method described previously (Bartholomew et al, Food Chem Toxicol 22:511, 1984): nitrate reductase prepared from E. Coli ATCC 25922 (Difco) was used to convert nitrate to nitrite. Total nitrite was quantified colorimetrically after reaction with the Griess reagent (Green et al, Annal BIochem 126:131, 1982). Creatinine was measured by the Ektachem method based on the enzymatic reaction of creatinine with creatinine iminohydrolase. RESULTS: Urine nitrite/nitrate concentrations varied widely (range: 38 to 298 μmol/mmol creatinine). No correlation was found between nitrite/nitrate concentrations and gestational age, postnatal age, birthweight or antibiotic treatment. Conversely, a transient but significant decrease in urinary nitrite/nitrate concentrations was found in 5 patients who received fresh frozen plasma (basal values 169.2±71.7, day of transfusion 65±54.1, p

Urinary nitrite/nitrate concentration provides reasonable estimate of whole-body nitric oxide (NO) synthesis. We tested the hypothesis that NO synthesis undergo maturational changes after birth in 10 preterm infants (mean GA 33.2±2.5 w, range 30-37; BW 2160-445 g, range 1440-3010) admitted to NICU. The newborns were delivered spontaneously (n=5) and by cesarean section(n=5). No patient had neonatal asphyxia (Apgar score at 1':8±0.8; at 5':8.5±1), respiratory disease, diarrhea, or conditions reported to alter urinary nitrite/nitrate concentrations. Daily 8-hour samples were collected during the first, third, and fifth day of life and kept at -20°C until the assay was performed. Nitrite/nitrate concentrations were measured spectrophotometrically according to a modification of a method described previously (Bartholomew et al, Food Chem Toxicol 22:511, 1984). Nitrate reductase prepared from E. Coli ATCC 25922 (Difco) was used to convert nitrate to nitrite. Total nitrite was quantified colorimetrically after reaction with the Griess reagent (Green et al, Annal Biochem 126:131, 1982). Creatinine was also measured by the Ektachem method based on the enzymatic reaction of creatinine with creatinine iminohydrolase. RESULTS: nitrite/nitrate concentrations (mean±SD in μmol/mmol creatinine) were: 1st day: 123.36±75.17; 3rd day: 135.01±63.22; 5th day: 109.94±40.36. No correlation was found between nitrite/nitrate concentrations and gestational age, postnatal age, birthweight or type of delivery. Urine nitrite/nitrate concentration varied widely as previously reported (Dolberg et al, Pediatr Res 37:31, 1995). Mean values remained substantially stable during the first 5 days of postnatal age. Urinary nitrite/nitrate levels are considered a reasonable estimate of in vivo conversion of L-arginine to nitric oxide. The present preliminary results suggest that NO synthesis from L-arginine may not undergo substantial developmental changes during the first 5 days postnatally.

A review of 253 patients treated with enteral nutrition support via tube feedings is presented for the purpose of evaluating the incidence of complications. Thirty patients, (11.7%) experienced either gastrointestinal, (6.2%) mechanical (3.5%), or metabolic (2.0%) complications. The recognition and treatment of such complications are discussed and it is concluded that tube feedings are safely tolerated by most patients; however, constant attention must be exerted to either avoid or recognize such complications.

It is well known that subjects homozygous for a rare silent allele of ADA may experience a severe combined immunodeficiency. By analogy we have investigated the possible relationship of normal ADA polymorphism with some situations, such as reproductive defects and fetomaternal interactions, in which immunological mechanisms may play an important role. A total of 572 consecutive newborns, 93 consecutive low birthweight infants, 46 couples with unexplained habitual abortion, and 24 couples with unexplained sterility were studied. The proportion of ADA 2-1 phenotype was reduced in couples with reproductive defects. In the sample of consecutive newborns the proportion of ABO incompatible babies was higher among ADA 2-1 than among ADA 1 types. ADA 2-1 phenotype was also associated with a reduction in the variability of gestational length. These associations were much more marked among male than among female babies. The proportion of ADA 2-1 was significantly lower in low birthweight infants than in the consecutively studied infants and normal adults. The present data suggest that biochemical variability resulting from the normal ADA polymorphism may be, at least in part, responsible for the variability of some immunological functions and related physiological variables and pathological conditions. They also provide evidence in favour of a selective advantage of ADA heterozygotes.

A prospectively studied series of 1072 patients who received specialized nutritional support are presented to evaluate the patterns of such care in a large nonuniversity teaching center. Age, service, materials used, routes of administration, complications, assessment parameters, duration of treatment, diagnoses, and survival statistics are presented. Such patterns are considered to be of importance to medical scientists, basic researchers, hospital administrators, governmental agencies, and members of the health care insurance industry. (Journal of Parenteral and Enteral Nutrition 8:506-510, 1984)

A prospective study analyzing the complications in 307 patients who had specialized nutrition support administered by their private practitioners was performed and compared to other series in which a nutrition support service exclusively provided such care to patients. The mechanical complication rate of 4.6%, septic complication rate of 2.9%, and metabolic complication rate of 4.2% compared favorably with the reported literature. A new category of complications, the judgmental complication, is described and was 12.7% in the reported series. The Saint Barnabas Medical Center experience suggests that individual practitioners can satisfactorily administer intravenous specialized nutrition support if in fact an involved nutrition support service functions administratively and supportively in the background. (Journal of Parenteral and Enteral Nutrition8:385-390, 1983)