PDF superior Clinical, biochemical, and molecular findings in Argentinean patients with goitrous congenital hypothyroidism

was explained by Kanou et al. as the possible expression of an increased thyroidal type 2 iodothyronine deiodinase in patients with defective TG expression [39]. Serum TG con- centration was very useful in the characterization of this group as serum TG was low in relation to the degree of TSH stimulation suggesting the presence of TG synthesis defects. The absence of iodide discharge in the perchlorate test in these patients completed the figure for the suspected defect. In our analysis, eight patients were fully characterized and three carried only one mutation heterozygous [37, 38, 42]. The same considerations as we speculated for the TPO gene mutations could take account in this case. Exons 7 and 38 might be considered as hotspots for loss of function in the TG gene in our population and p.R277X the most prevalent finding.

The data collected included demographic informa- tion, gender, age at clinical symptom onset, age at diagnosis, consanguinity, number of siblings affec- ted by HT1 or with suggestive symptoms, and clini- cal and biochemical data at the time of diagnosis. When available, the histopathological findings from liver biopsies were recorded and their concordance with the definitive biochemical diagnosis was analy- zed. Some records were incomplete because the pa- tients were treated at other institutions. For the mortality rate analysis, patients were grouped into two categories according to the modality of treat- ment received (group 1: those who underwent liver transplantation; group 2: those who did not under- go liver transplantation).

Background and aims. There are certain areas of uncertainty regarding the best therapeutic approach in patients diagnosed with Wilson Disease (WD). Our aim was to assess treatment response to different thera- pies in a cohort of WD patients followed in a single center. Material and methods. This is an observatio- nal, descriptive study in which clinical, laboratory and imaging data are reviewed in a series of 20 WD patients with a median follow-up of 14 years. Type of presentation, treatment used, biochemical and copper homeostasis parameters were elicited. Results. Median age at diagnosis was 22 years. The most fre- quent form of presentation was hepatic (n = 10, 50%; mean age: 21.5 years), followed by neurological (25%; mean age: 34.5 years) and mixed (15%). The initial treatment in both symptomatic and asymptomatic patients at diagnosis was d-penicillamine in 90% and Zinc (Zn) in 10%, respectively. Patients who were main- tained on d-penicillamine for the whole period had complete biochemical normalization (baseline ALT: 220 IU/l; last follow up 38 IU/l). In contrast, patients in whom d-penicillamine was switched to Zn, irrespective of the cause, did not show a complete biochemical remission (baseline ALT: 100 IU/l vs. 66 IU/l at last follow-up). Conclusions. Treatment was found to be effective in most cases regardless of the drug used. However, side effects were common in those treated with d-penicillamine agents, and required switching to zinc. Therapy with zinc was well tolerated and appeared to have a good efficacy. However, in 33%, a complete normalization of liver enzymes was never reached.

Results: The pre- and post-treatment clinical and biochemical aspects are, respectively: 52 vs. 51 years of age, TSH (mIU/mL) 5.42 vs. 1.72, (p<0.5), FT4 1.13 vs. 1.21 ng/dL, creatinine 0.93 vs. 0.82 mg/dL (p < 0.5), glucose 84 vs. 87 mg/dL, total cholesterol 202 vs. 190 mg/dL, triglycerides 127 vs. 124 mg/dL, LDL-c 120 vs. 110 mg/dL, HDL-c 55 vs. 54 mg/dL and uremia 36 vs. 35 mg/dL.

performed an analysis of the association with ordinal or dichotomous statistical management of the main biochemical dialytic variables and the HRQoL. The independent risk factors associated with P-HRQoL in the analysis included the time spent on hemodialysis (OR = 1.02; 95% CI: 1.00-1.04; p = 0.02), use of a venous catheter vs. arteriovenous fistula for vascular access (OR = 3.2; 95% CI: 1.36-7.75; p = 0.01), and serum levels of albumin below 4 g/dl (OR = 3.55; 95% CI: 1.44-8.7; p < 0.01). In this type of multi- variate analysis, Kt/V (Kt/V > or < 1.4) was ana- lyzed dichotomously, and hemoglobin (Hb < 9 g/dl vs. Hb 9-11 g/dl vs. Hb > 11 g/dl), serum calcium (Ca < 8.5 mg/dl vs. Ca = 8.5-10 mg/dl vs. Ca > 10 mg/ dl), and serum phosphorus levels (P < 3.5 mg/dl vs. P = 3.5-5.5 mg/dl vs. P > 5.5 mg/dl) were analyzed ordinally and were not associated with P-HRQoL in our population. In conclusion, these findings indicate that, while clinical and biochemical measurements provide important information to the physician regarding clinical outcomes, these parameters weakly corre- late with HRQoL of patients with ESRD who receive hemodialysis. In this regard, the subjective evalua- tion that the individuals produce regarding their own quality of life plays an important role, and similar health states may correspond to different percep- tions of the HRQoL.

Beloranib, a drug for obesity, developed by Zafgen, is showing promising results with regard to the control of the obesity associated with the Prader-Willi Syndrome. The findings of a limited clinical trial, both in the number of patients and its duration, have shown that Beloranib decreased lipid synthesis, and increased lipolysis, obtaining a clear reduction in the fat mass of the people affected by this rare syndrome.

PubMed and the Cochrane Library were searched for randomized controlled trials, systematic reviews, meta-analyses, and clinical practice guide- lines for the period from November 5, 2012, through July 2014. The disease and intervention search terms were those that were used for the 2013 guideline update. An update committee (members listed in Appendix Table A1, online only), formed in accordance

Although the diagnosis is clinical, molecular study allows confirmation Pathogenic variants in MECP2 gene are the cause of 80-90% of cases of classical RTT and about 40% of atypical RTT. Most of the variants are located in exons 3 and 4, and 99% of cases, they are de novo events 1-6 . The remaining cases have been asso-

A descriptive analysis of all the collected variables was conducted. Numerical variables are presented with their average ± standard deviation, median and range. Qualitative variables are expressed as a percentage and a 95% confidence interval (CI). For the comparison of quantitative variables, the following tests were used: Kolmogorov–Smirnov test, Student test, Mann–Whitney test or variance analysis. For qualitative variables, the square chi test or Fisher's exact test was used. To determine the variables associated with events of interest (bilateral affection), a multivariate logistic regression analysis was performed. The statistical analysis was conducted with SPSS 15.0 and Epidat 3.1 software for Windows.

mutations have been registered in the Leiden Open Variation Database (LOVD). RB1 mutations show an extensive heterogeneity without hot spots. Different techniques have been used to identify genetic variations in the RB1 gene. The single strand conformation polymorphism (SSCP) technique has been used to screen for mutations before confirmatory sequencing is performed (11-15). This technique is based on the sequence-dependent migration patterns of single- stranded DNA fragments as they migrate through nondenaturing polyacrylamide gel electrophoresis. The aim of this study was to identify mutations in the RB1 gene in Colombian patients with sporadic retinoblastoma by PCR-SSCP followed by sequence. In this study we report the identification of three new RB1 gene mutations in four patients with sporadic retinoblastoma in Colombia. We also describe a new RB1 gene variant that increases the small number of polymorphisms reported for this gene.

These clinical practice guidelines summarize the rec- ommendations of the American Association of Clinical Endocrinologists for the diagnostic evaluation of hyper- thyroidism and hypothyroidism and for treatment strate- gies in patients with these disorders. The sensitive thyroid- stimulating hormone (TSH or thyrotropin) assay has become the single best screening test for hyperthyroidism and hypothyroidism, and in most outpatient clinical situa- tions, the serum TSH is the most sensitive test for detect- ing mild thyroid hormone excess or deficiency. Therapeutic options for patients with Graves’ disease include thyroidectomy (rarely used now in the United States), antithyroid drugs (frequently associated with relapses), and radioactive iodine (currently the treatment of choice). In clinical hypothyroidism, the standard treat- ment is levothyroxine replacement, which must be tailored to the individual patient. Awareness of subclinical thyroid disease, which often remains undiagnosed, is emphasized, as is a system of care that incorporates regular follow-up surveillance by one physician as well as education and involvement of the patient. (Endocr Pract. 2002;8:457- 469)

Various studies have been initiated to investigate the effect of pegylated interferon in HIV–HCV coinfected pa- tients. The efficacy and safety for HIV–HCV coinfected patients of a combination of interferon alfa-2b (3 MIU three times per week) and ribavirin (800 mg/24 h) were compared with that of a combination of pegylated inter- feron alfa-2b (1.5 µg/kg body weight once per week) and ribavirin (800 mg/24 h). A preliminary report 64 indicated

Approximately 87% of the patients studied herein had severe ocular defects including myopia, nystagmus and macular colobo- mata (Tables 1, 2 and 3). This finding is similar to those reported for other series [15,29]. Therefore, we can conclude that these ocular abnormalities are characteristics of FHHNC patients with CLDN19 mutations. Four of our patients (ages between 5.7 and 7.9) did not present ocular abnormalities. Two of these patients (6.8 and 7.9 years old) were homozygous for p.G20D and two sisters (5.7 and 7.8 years old) were heterozygous for this mutation. One of the Spanish patients with mutation p.G20D, F51-II-1, studied by Konrad and his associates [15], also persisted at 16 years of age without ocular lesions. We suggest that there must be other unknown factors associated with the ocular phenotype. Claudin-19 is expressed at high levels in the retinal pigment epithelium linking dysfunction of claudin-19 to the phenotype of visual impairment [15]. Claudin-19 is also expressed in the tight junction of Schwann cells where it could participate in electrical insulation of axons [16]. Claudin-19-deficient mice exhibited behavioral abnormalities that could be due to peripheral nervous system deficit [16]. In a recent study, Faguer and colleagues [35] reported muscular-exercise intolerance with cramps, weakness and electromyographical alterations in two FHHNC patients with severe ocular defects. We observed no neuromuscular symptoms in our patients with the exception of patient P393 who showed

Laboratory tests should be dimensioned and orien- ted to establish the diagnosis (elevation of CK). Excep- tionally, and on suspicion of rhabdomyolysis due to excessive CK increase, renal function could be moni- tored. However, it is important to be aware of this rare but severe complication, suggested by dark urine and positive blood on urine dipstick in the absence of red blood cells on microscopic examination of urine.. An accurate diagnosis prevents invasive studies and unne- cessary hospitalizations, while avoiding greater anxiety in the patient and his family.

In the clinical field, two retrospective studies analysed the role of MCT in OC. Sánchez-Muñoz et al suggested that the combination of metronomic oral Cy plus bevacizumab in heavily pretreated patients with recurrent OC could be an option, with a response rate of 40% and a Clinical Benefit of 48% [30]. Also, Ferrandina et al showed the efficacy and safety of metronomic oral Cy in heavily treated relapsed OC; the patients responding to MCT showed higher PFS and OS compared to those who had stable disease or disease progression [31]. Moreover, a case report by Samaritani et al presented a patient with stage-IIIC OC treated with metronomic Cy, who showed an impres- sive PFS of 65 months, without side effects, after non-response to standard chemotherapy with platins, taxans, and topotecan [23]. Those results are very encouraging and the prolonged PFS accomplished agrees with the ones herein described. The non-randomized clinical trial conducted by El-husseiny et al, setting metronomic Cy and methotrexate as maintenance therapy in patients who achieved complete response after platinum and paclitaxel regimens, showed that the PFS was significantly higher (18 months) in the treatment arm than that of the observational one (15 months). Also, no grade III–IV toxicities were observed and the treatment regimen was safe and well tolerated [32]. Furthermore, the addition of bevacizumab (10 mg/kg) IV every two weeks to metronomic oral Cy 50 mg/d in recurrent OC showed a median PFS of 7.2 months, with mild toxicity [33].

IL-2 in patients with metastatic breast carcinoma: a pilot clinical trial. Oncogene Her2[r]

Opioid-induced central nervous system (CNS) adverse effects are related to the anticholinergic actions of opioids, with inhibition of central cholinergic activity in multiple cortical and subcortical regions of the brain, in addition to an imbalance in CNS cholinergic and dopaminergic sys- tems [29]. The accumulation of toxic opioid metabolites has also been implicated (Fig. 2). Using the example of morphine as the “gold standard” opioid, the major metabo- lite (44%–55%), morphine-3-glucuronide (M-3-G), has no ␮ -opioid binding and consequently no analgesic properties [37, 41]. M-3-G is thought to be responsible for the cluster of OIN symptoms described above. However, the evidence for this is conflicting. Gong et al. [42], in 1992, reported that M-3-G did not produce excitatory and antianalgesic effects in rats, and Penson et al. [43] more recently, in 2001, did not induce neurotoxicity when small i.v. doses of M-3-G were injected into healthy volunteers. Normorphine, another nonopioid-binding neurotoxic metabolite, accounts for only approximately 5% of morphine metabolism [44]. However, this mediator may play a more prominent role in

O b j e c t i v e : To estimate the adequacy of iodide intake in Wanda Misiones through the conventional parame- ters of ioduria and goiter prevalence in scholars as well as with the distribution of TSH neonatal levels as perfor- med for the hypothyroidism screening program in newborns. Population and methods: Height , and BMI and weight were assessed in 502 scholars aged 5 to 14 and expressed as SDS. In 419 of them (215 female) thyro i d volume was evaluated and classified according to WHO (9). In 114 children iodide urinary concentration was measured in casual urine samples by Sandell y Kolthof method modified by Pino (17). Neonatal screening pro- gram for congenital hypothyroidism is carried out in the region measuring TSH in filter paper samples with IFMA DELFIA. Since 2000 7.102 newborn have been screened. TSH level’s distribution of the 18 months prior to this study (n 267) were evaluated. Criteria suggested by WHO to indicate iodide deficiency were applied. Results: Height, weight and BMI were normal for the chronological age according to Argentinean population parameters. Goitre prevalence was 6.2 % (7.3 % in girls and 5.3 % in boys), higher that expected for a iodide suf- ficient area. Iodide urine median levels were 239 ug/l with a distribution that excluded iodide deficiency. Neonatal screening program detected 5 congenital hypothyroid children out of the 7102 newborn studied. All of them were early and adequately treated. Only 1.4 % of the 267 samples were > 5 µU/ml, excluding iodide defi- ciency. Conclusion: Iodide intake in Wanda, Misiones, is adequate as shown by the findings of iodide urine con- centration and TSH neonatal levels. A higher prevalence of goitre than expected for this situation, could be ex- plained by dietary intake of goitrogen food as mandioca. Congenital hypothyroidism screening program in this region was extremely effective. The possibility of using its results for iodide intake supervision is an additional benefit to the one of early prevention of mental retardation.

Hepatitis E virus infection in patients with clinical diagnosis of viral hepatitis in Colombia ... 354[r]

Prolactin (PRL) is a peptide hormone pro- duced and secreted by the lactotropic cells of the anterior pituitary. In mammals, PRL is essen- tially involved in the control of reproduction (1). Particularly, in the domestic dog this hormone regulates gonadal function, mammary develop- ment and reproductive behavior (2, 3). Prolactin secretion is regulated by a constant inhibitory tone of hypothalamic origin, whose main me- diator is dopamine. Dopamine acts on D2 type dopamine receptors on the lactotropic cells. Pro- lactin secretion is further regulated by numerous neurotransmitters and peptide factors. They may have either an inhibitory or stimulatory effect. The latter are histamine, oxytocin, vasopressin, thyrotropin releasing hormone (TRH), estrogens, GnRH and opiods (1).