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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.

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)

Aims: To determine in a case-control study possible associations between the development of acute renal failure in preterm newborns and therapeutic interventions, particularly drug treatments. Methods: The study population was 172 preterm infants of ,38 weeks gestation; 71 had acute renal failure and 101 were controls closely matched for gestational age and birth weight. Maternal and neonatal information was collected for both groups through questionnaires and interviews. Routine data on renal variables were also collected. Univariate and multivariate logistic regression analyses were performed. Results: Very low birthweight infants were at high risk of acute renal failure (79% of cases were ,1500 g). However, the acute renal failure was transient. Mothers of infants with acute renal failure received more drugs during pregnancy and delivery (mainly antibiotics and non-steroidal anti-inflammatory drugs). Of the possible therapeutic interventions, intubation, catheterisation, and phototherapy were mainly applied to case subjects. A low Apgar score and patent ductus arteriosus were diagnosed in a greater percentage of neonates with acute renal failure. Moreover, in the first few days of life and before diagnosis of acute renal failure, case subjects received more drugs (antibiotics, non-steroidal anti-inflammatory drugs, and diuretics) and for a longer time. In the multivariate logistic analysis, medullary hyperechogenicity (odds ratio (OR) 4.491; 95% confidence interval (CI) 1.879 to 10.731) and ceftazidime administration (OR 5.082; 95% CI 1.493 to 17.297) were associated with a greater risk of acute renal failure. Conclusions: The results suggest the need for careful monitoring of very low birthweight infants and attention to drug treatments, as it is difficult to differentiate between normality and renal failure in the first few days of life.

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.

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.

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.

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 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)

Eighty low birthweight infants (1500 to 2500 g) were randomly assigned to a group given oral agar and a control group. The study was first performed in 24 agar-fed babies and 24 control babies. The treated infants received a daily total amount of 600 mg/kg of agar beginning at 12 hours of age, for 7 days. In the later stage of the trial, 16 agar-fed babies and 16 control babies were investigated. The total daily amount of agar was raised to 700 mg/kg, beginning at 6 hours of age for 7 days. No complications were observed with the administration of agar. Serum bilirubin levels were not significantly lower in the agar-fed infants. We conclude that agar supplemented feeding is not indicated in the management of hyperbilirubinaemia in low birthweight newborn infants.