Serum Vitamins in Adult Patients With Short Bowel Syndrome Receiving Intermittent Parenteral Nutrition

Background: Short bowel syndrome (SBS) occurs after massive intestinal resection, and parenteral nutrition (PN) therapy may be necessary even after a period of adaptation. The purpose of this study was to determine the vitamin status in adults with SBS receiving intermittent PN. Methods: The study was conducted on hospitalized adults with SBS who were receiving intermittent PN therapy (n = 8). Nine healthy volunteers, paired by age and sex, served as controls. Food ingestion, anthropometry, plasma folic acid, and vitamins B(12), C, A, D, E, and K were evaluated. Results: The levels of vitamins A, D, and B(12) in both groups were similar. SBS patients presented higher values of folic acid (21.3 +/- 4.4 vs 14.4 +/- 5.2, P = .01) and lower values of vitamin C (0.9 +/- 0.4 vs 1.2 +/- 0.3 mg/dL, P = .03), alpha-tocopherol (16.3 +/- 3.4 vs 24.1 +/-+/- 2.7 mu mol/L, P < .001), and phylloquinone (0.6 +/- 0.2 vs 1.0 +/- 0.5 nmol/L, P < .03). Eight-seven percent of patients had vitamin D deficiency, and all patients presented with serum vitamin E levels below reference values. Conclusions: Despite all efforts to offer all the nutrients mentioned above, SBS patients had lower serum levels of vitamins C, E, and K, similar to those observed in patients on home PN. These findings suggest that the administered vitamins were not sufficient for the intermittent PN scheme and that individual adjustments are needed depending on the patient`s vitamin status. (JPEN J Parenter Enteral Nutr. 2011;35:493-498)

Inhibition of Expression of HTLV-1 Structural Genes Mediated by Short Hairpin RNA In Vitro

Background: Human T-lymphotropic virus 1 (HTLV-1) is associated with the T-cell malignancy known as adult T-cell leukemia! lymphoma (ATLL) and with a disorder called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Currently, the treatment of these diseases is based on symptom relief. RNA interference (RNAi) technology has been described as an efficient mechanism for development of new therapeutic methods. Thus, the aim of this study was to evaluate the inhibition of HTLV-1 structural proteins using short hairpin RNAs (shRNAs) expressed by non-viral vectors. Materials and Methods: Reporter plasmids that express enhanced green fluorescent protein-Gag (EGFP-Gag) and EGFP-Env fusion proteins and vectors that express shRNAs corresponding to the HTLV-1 gag and env genes were constructed. shRNA vectors and reporter plasmids were simultaneously transfected into HEK 293 cells. Results: Fluorescence microscopy, flow cytometry and real-time PCR showed that shRNAs were effective in inhibiting the fusion proteins. Conclusion: These shRNAs are effective against the expression of structural genes and may provide an approach to the development of new therapeutic agents.

Consequences of lifetime isolated growth hormone (GH) deficiency and effects of short-term GH treatment on bone in adults with a mutation in the GHRH-receptor gene

Growth hormone (GH) influences bone mass maintenance. However, the consequences of lifetime isolated GH deficiency (IGHD) on bone are not well established. We assessed the bone status and the effect of 6 months of GH replacement in GH-naive adults with IGHD due to a homozygous mutation of the GH-releasing hormone (GHRH)-receptor gene (GHRHR). We studied 20 individuals (10 men) with IGHD at baseline, after 6 months of depot GH treatment, and 6 and 12 months after discontinuation of GH. Quantitative ultrasound (QUS) of the heel was performed and serum osteocalcin (OC) and C-terminal cross-linking telopeptide of type I collagen (ICTP) were measured. QUS was also performed at baseline and 12 months later in a group of 20 normal control individuals (CO), who did not receive GH treatment. At baseline, the IGHD group had a lower T-score on QUS than CO (-1.15 +/- 0.9 vs. -0.07 +/- 0.9, P < 0.001). GH treatment improved this parameter, with improvement persisting for 12 months post-treatment (T-score for IGHD = -0.59 +/- 0.9, P < 0.05). GH also caused an increase in serum OC (baseline vs. pGH, P < 0.001) and ICTP (baseline vs. pGH, P < 0.01). The increase in OC was more marked during treatment and its reduction was slower after GH discontinuation than in ICTP. These data suggest that lifetime severe IGHD is associated with significant reduction in QUS parameters, which are partially reversed by short-term depot GH treatment. The treatment induces a biochemical pattern of bone anabolism that persists for at least 6 months after treatment discontinuation.

Muscle mass gain observed in patients with short bowel syndrome subjected to resistance training

Few studies are available about the evaluation of resistance training in patients with protein-energy malnutrition. To assess the effects of resistance training on the recovery of nutritional status of patients with short bowel syndrome, with a small bowel remnant of less than 100 cm, 9 patients of both sexes with protein-energy malnutrition after extensive resection of the small bowel were submitted to resistance training of progressive intensity consisting of concentric and eccentric work exercises for the upper limbs, trunk, and lower limbs, with the individuality and limitations of each patients being respected. Food consumption was monitored by 24-hour food recall performed during the initial phase of the study, before and 7 and 14 weeks after physical training, and by a dietary record for a period of 3 days of oral feeding. The nutrients administered by the enteral and parenteral route were recorded. A significant increase in total arm area (P <= .01) and fat-free mass (P <= .01) was observed as determined by computed tomography. An increase in total energy ingestion and carbohydrate consumption (P <= .01) was also observed. In addition, the activity of the enzyme carnosinase was increased after resistance training (P <= .01). The present results show that resistance training in patients with short bowel syndrome and protein-energy malnutrition can be considered to be a part of the nonmedicamentous treatment of these patients, leading to better nutrient use and to a gain of lean mass. (c) 2008 Elsevier Inc. All rights reserved.

Short-Term Carbohydrate-Restricted Diet for Weight Loss in Severely Obese Women

Weight loss in bariatric pre-surgery period reduces surgical complications, surgery time, blood loss, and length of hospital stay. Carbohydrate-restricted diets have been used as an alternative for weight loss. We tested the efficacy of a low-calorie carbohydrate-restricted diet (RD) for short-term weight loss in women with severe obesity and evaluate its metabolic effects in relation to a conventional low-calorie diet (CD). The subjects received a 1,200-kcal diet with or without carbohydrate restriction for a period of 1 week in the hospital. Nineteen obesity class III women were distributed into two groups: experimental (n = 10) and control (n = 9). The following variables were assessed at the beginning and end of the study: anthropometric measurements, body composition, resting energy expenditure, substrate oxidation, and biochemical tests. Compared with CD, RD led to larger weight loss (2.6 and 4.4 kg, respectively; p = 0.01) and waist circumference reduction (p < 0.01). Among the assessed biochemical indicators, only plasma and urine acetone levels were different (p < 0.01); higher values were found in the experimental group with no symptoms and other diet-related complaints. There was also a significant decrease in triglycerides and carbohydrate oxidation, as well as a significant enhancement in lipid oxidation in the RD group. Short-term RD was more efficient than CD regarding quick weight loss and waist circumference reduction, which may favor gastroplasty. Also, RD did not lead adverse metabolic effects.

Adjunctive benefits of systemic etoricoxib in non-surgical treatment of aggressive periodontitis: Short-term evaluation

Background: This pilot study assessed the effect of short-duration treatment with etoricoxib as adjuvant therapy to scaling and root planing (SRP) on the clinical and radiographic parameters and prostaglandin E-2 (PGE(2)) levels in aggressive periodontitis. Methods: Subjects were randomly allocated to test or control treatment (n = 10 in each group) and submitted to SRP and treatment with etoricoxib, 120 mg/day, or placebo for 7 days. Probing depth, clinical attachment level (CAL), gingival recession, visible plaque index, bleeding on probing, linear distance (LD) from the cemento-enamel junction to the alveolar crest, and analysis of the gray levels were recorded before and 1 month after the therapies. The prostaglandin E-2 (PGE(2)) level in the gingival crevicular fluid (GCF) was measured by radioimmunoassay at the beginning of the study and 7 and 30 days after treatment. Results: No significant difference in the clinical parameters was observed between the groups at the end of the experimental period, although both groups presented significant improvement in all variables examined. There was a decrease in CAL from 5.54 +/- 0.47 mm to 3.59 +/- 0.53 mm in the test group and from 5.92 +/- 1.10 mmto 3.69 +/- 0.80 mm in the control group. A significant reduction in PGE(2) was found after 7 days of treatment. LD differed between the groups. Conclusion: Etoricoxib did not promote additional improvement in the clinical parameters; however, it produced an initial reduction in the PGE(2) levels in the GCF, which could be related to the discrete improvement in the bone condition.

A novel role for MNTB neuron dendrites in regulating action potential amplitude and cell excitability during repetitive firing

Principal cells of the medial nucleus of the trapezoid body (MNTB) are simple round neurons that receive a large excitatory synapse (the calyx of Held) and many small inhibitory synapses on the soma. Strangely, these neurons also possess one or two short tufted dendrites, whose function is unknown. Here we assess the role of these MNTB cell dendrites using patch-clamp recordings, imaging and immunohistochemistry techniques. Using outside-out patches and immunohistochemistry, we demonstrate the presence of dendritic Na(+) channels. Current-clamp recordings show that tetrodotoxin applied onto dendrites impairs action potential (AP) firing. Using Na(+) imaging, we show that the dendrite may serve to maintain AP amplitudes during high-frequency firing, as Na(+) clearance in dendritic compartments is faster than axonal compartments. Prolonged high-frequency firing can diminish Na(+) gradients in the axon while the dendritic gradient remains closer to resting conditions; therefore, the dendrite can provide additional inward current during prolonged firing. Using electron microscopy, we demonstrate that there are small excitatory synaptic boutons on dendrites. Multi-compartment MNTB cell simulations show that, with an active dendrite, dendritic excitatory postsynaptic currents (EPSCs) elicit delayed APs compared with calyceal EPSCs. Together with high- and low-threshold voltage-gated K(+) currents, we suggest that the function of the MNTB dendrite is to improve high-fidelity firing, and our modelling results indicate that an active dendrite could contribute to a `dual` firing mode for MNTB cells (an instantaneous response to calyceal inputs and a delayed response to non-calyceal dendritic excitatory postsynaptic potentials).

Distribution of fentanyl in the placental intervillous space and in the different maternal and fetal compartments in term pregnant women

Fentanyl is used in obstetrical practice to promote analgesia and anesthesia during labor and in cesarean delivery, with rapid and short-term effects. To determine fentanyl concentrations in maternal plasma, in the placental intervillous space, and in the umbilical artery and vein in term pregnant women. Ten healthy pregnant women underwent epidural anesthesia with fentanyl plus bupivacaine and lidocaine, and fentanyl concentrations were determined in the various maternal and fetal compartments, including the placental intervillous space, which has not been previously studied in the literature. The ratios of fentanyl concentrations in the various maternal and fetal compartments revealed an 86% rate of placental fentanyl transfer. The highest fentanyl concentrations were detected in the placental intervillous space, being 2.19 times higher than in maternal plasma, 2.8 times higher than in the umbilical vein and 3.6 times higher than in the umbilical artery, with no significant differences between the umbilical vein and artery, demonstrating that there was no drug uptake by fetal tissues nor metabolism of the drug by the fetus despite the high rates of placental transfer. The present study demonstrated that the placental intervillous space acted as a site of fentanyl deposit, a fact that may be explained by two hypotheses: (1) the blood collected from the placental intervillous space is arterial and, according to some investigators, the arterial plasma concentrations of the drugs administered to patients undergoing epidural anesthesia are higher than the venous concentrations, and (2) a possible role of P-glycoprotein (P-gp).

Short Report: Co-Infection with Paracoccidioidomycosis and Human Immunodeficiency Virus: Report of a Case with Esophageal Involvement

Paracoccidioiodomycosis (PCM) is a systemic and deep mycosis endemic in Latin America, especially in Brazil. In patients infected with human immunodeficiency virus (HIV), PCM can manifest with prominent involvement of the reticuloendothelial system. There are no reports in the literature of esophageal involvement by PCM in that population. We report a case of PCM with pulmonary and esophageal involvement without radiologic evidence of an esophageal-bronchial fistula in an HIV-infected patient.

Comparison of clinical features and drug therapies among European and Latin American patients with juvenile dermatomyositis

Objective To compare the demographic features, presenting manifestations, diagnostic investigations, disease course, and drug therapies of children with juvenile dermatomyositis (JDM) followed in Europe and Latin America. Methods Patients were inception cohorts seen between 1980 and 2004 in 27 paediatric rheumatology centres. The following information was collected through the review of patient charts: sex; age at disease onset; date of disease onset and diagnosis; onset type; presenting clinical features; diagnostic investigations; course type; and medications received during disease course. Results Four hundred and ninety patients (65.5% females, mean onset age 7.0 years, mean disease duration 7.7 years) were included. Disease presentation was acute or insidious in 57.1% and 42.9% of the patients, respectively. The course type was monophasic in 41.3% of patients and chronic polycyclic or continuous in 58.6% of patients. The more common presenting manifestations were muscle weakness (84.9%), Gottron`s papules (72.9%), heliotrope rash (62%), and malar rash (56.7%). Overall, the demographic and clinical features of the 2 continental cohorts were comparable. European patients received more frequently high-dose intravenous methylprednisolone, cyclosporine, cyclophosphamide, and azathioprine, while methotrexate and antimalarials medications were used more commonly by Latin American physicians. Conclusion The demographic and clinical characteristics of JDM are similar in European and Latin American patients. We found, however, several differences in the use of medications between European and Latin American paediatric rheumatologists.

The Provisional Paediatric Rheumatology International Trials Organisation/American College of Rheumatology/European League Against Rheumatism disease activity core set for the evaluation of response to therapy in juvenile dermatomyositis: A prospective validation study

Objective. To validate a core set of outcome measures for the evaluation of response to treatment in patients with juvenile dermatomyositis (DM). Methods. In 2001, a preliminary consensus-derived core set for evaluating response to therapy in juvenile DM was established. In the present study, the core set was validated through an evidence-based, large-scale data collection that led to the enrollment of 294 patients from 36 countries. Consecutive patients with active disease were assessed at baseline and after 6 months. The validation procedures included assessment of feasibility, responsiveness, discriminant and construct ability, concordce in the evaluation of response to therapy between physicians and parents, redundancy, internal consistency, and ability to predict a therapeutic response. Results. The following clinical measures were found to be feasible, and to have good construct validity, discriminative ability, and internal consistency; furthermore, they were not redundant, proved responsive to clinically important changes in disease activity, and were associated strongly with treatment outcome and thus were included in the final core set: 1) physician`s global assessment of disease activity, 2) muscle strength, 3) global disease activity measure, 4) parent`s global assessment of patient`s well-being, 5) functional ability, and 6) health-related quality of life. Conclusion. The members of the Paediatric Rheumatology International Trials Organisation, with the endorsement of the American College of Rheumatology and the European Leauge Against Rheumatism, propose a core set of criteria for the evaluation of response of therapy that is scientifically and clinically relevant and statistically validated. The core set will help standardize the conduct and reporting of clinical trials and assist practitioners in deciding whether a child with juvenile DM has responded adequately to therapy.