Multivisceral Transplantation Rehabilitation Program-Case Report.

Multivisceral transplantation is the treatment for multiple abdominal organ failure. The patient experiences reduced food intake and absorption of nutrients, contributing to weight loss and decreased muscle mass, reducing functional capacity. A physical and nutritional rehabilitation program based on adequate caloric intake associated with supervised physical exercise seems to support a gain of muscle mass, re-establishing its capacity and functional independence. A rehabilitation program was carried out, consisting of low-intensity aerobic exercise on treadmill, exercises of global strengthening (50% of 1 maximum repetition [1RM], with progressive increase), and nutritional monitoring (oral hypercaloric diet, hyperproteic supplementation daily and after exercise). Initial and final evaluation included weight, muscle mass index, brachial circumference (BC), tricipital cutaneous fold (TCF), hand grip strength (HGS), 6-minute walk test (6MWT), 1RM, vital capacity (VC), and respiratory muscle strength. After the program, functional capacity was evaluated through the 6MWT (92%), 1RM test, VC (55%), respiratory muscle strength, HGS at 5 kg, weight gain (4.75%), increase of BC in 2 cm, and TCF in 2 mm. The program contributed to functional independence, improved quality of life, and social reintegration, suggesting the importance of a supervised physical activity program associated with adequate nutritional intake after multivisceral transplantation.

Time of Dropout From the Liver Transplant List in Patients With Hepatocellular Carcinoma: Clinical Behavior According to Tumor Characteristics and Severity of Liver Disease.

BACKGROUND: Prolonged time on the waiting list affects post-transplant survival of patients with hepatocellular carcinoma (HCC). However, it is not yet known which patients will be at higher risk for early dropout from the list. We investigate specific risk factors for early waiting list dropout in patients with HCC. METHODS: This was a single-center, intention-to-treat analysis of adults with HCC, within the Milan criteria, from July 2006 through September 2013. Patients were divided into groups according to waiting list time. The main end point was dropout from the list. RESULTS: The dropout rates of the study cohort at 3, 6, and 12-months were 6.4%, 12.4%, and 17.7%, respectively. Patients who dropped out from the list tended to be older, with blood types A and O, and with higher Child-Pugh and Model for End-Stage Liver Disease (MELD) scores. They also had larger nodules, responded poorly to trans-arterial chemo-embolization (TACE), and had a higher alpha-fetoprotein. Those with blood types B and AB appeared to be protected for dropout (odds ratio [OR] = 0.21, P = .02). Patients who responded to TACE were also protected (OR = 0.22, P < .001). When we looked into time to dropout, the only baseline characteristic that stood out was a higher MELD score (13 for those dropping out up to 90 days vs 10 for those dropping out after 180 days, P = .0025). CONCLUSIONS: We conclude that patients who drop out early from the list are primarily driven by the severity of liver disease. Patients who had progressive HCC had a high tumor load and poor response to loco-regional therapies, dropping out from the list after 180 days of inclusion.

Bioequivalence studies for two different strengths of montelukast in healthy volunteers: 10 mg film-coated tablets and 5 mg chewable tablets.

In order to assess the bioequivalence of 2 different formulations of montelukast, a pivotal trial for the montelukast 10 mg film-coated tablets formulation and a pivotal trial for the montelukast 5 mg chewable tablets formulation were conducted.For the 10 mg study, 34 healthy subjects were enrolled in a single centre, randomised, single-dose, open-label, 2-way crossover study, with a minimum washout period of 7 days, while for the 5 mg study, 42 healthy subjects were included in another study with a similar design. For both studies, plasma samples were collected up to 24 h post-dosing and drug levels were determined by reverse liquid chromatography and detected by tandem mass spectrometry detection.Pharmacokinetic parameters used for bioequivalence assessment, area under the concentration-time curve from time zero to time of last non-zero concentration (AUC0-t) and from time zero to infinity (AUC0-inf) and maximum observed concentration (Cmax), were determined from the drug concentration data using non-compartmental analysis.In the 10 mg study, the 90% confidence intervals obtained by analysis of variance were 99.62-120.51% for Cmax, 102.25-117.37% for AUC0-t and 101.96-116.67% for AUC0-inf, which were within the predefined acceptable range of 80.00-125.00%.In the 5 mg study, the 90% confidence intervals were 91.14-98.46% for Cmax, 93.02-98.42% for AUC0-t and 93.09-98.63% for AUC0-inf, which were within the predefined acceptable range of 80.00-125.00%.Bioequivalence between formulations was concluded both in terms of rate and extent of absorption for both strengths.

Bioequivalence of two formulations of escitalopram.

Escitalopram, CAS registry number 128196-01-0 is an orally administrated selective serotonin reuptake inhibitor (SSRI).The objective of this trial was to assess bioequivalence between an escitalopram formulation manufactured by Grupo Tecnimede and that of a European reference formulation, while evaluating both formulations' tolerability as a secondary objective.24 healthy subjects were enrolled in a single centre, randomised, single-dose, open-label, 2-way crossover study. Drug levels were determined by reverse liquid chromatography and detected by tandem mass spectrometry detection, LC-MS/MS method. Pharmacokinetic parameters used for bioequivalence assessment were determined from the drug concentration data using non-compartmental analysis.Mean±Standard deviation (SD) Cmax values were 18.89±5.06 ng/mL and 18.45±5.05 ng/mL for reference and test, respectively. AUClast was 577.16±196.20 ng · h/mL after the administration of the reference and 577.69±220.88 ng · h/mL for the test. AUCinf was 595.66±203.80 ng · h/mL after the administration of the reference 596.19±235.47 ng · h/mL for the test.The 90% confidence intervals obtained by analysis of variance were 92.38-103.38% for Cmax, 94.10-104.37% for AUClast and 93.80-104.09% for AUCinf, which were within the predefined acceptable range of 80.00-125.00%. Both formulations were well tolerated, with no major side effects and no relevant differences in safety profiles observed between the preparations.The design of the study was adequate to determine the pharmacokinetic parameters of the test and the reference formulations. Bioequivalence between formulations was concluded both in terms of rate and extent of absorption.

Trema micrantha toxicity in horses in Brazil.

After ingesting green leaves of T. micrantha, 2 horses showed apathy, locomotor deficit, blindness, recumbency, paddling, coma and death. The main gross findings were scattered haemorrhages, enhanced lobular pattern of the liver, and cerebral oedema. Histological changes included disseminated haemorrhages, massive hepatocellular necrosis, neuronal degeneration, Alzheimer type II astrocytes and cerebral perivascular oedema. Clinicopathological findings which were comparable with those observed in Trema micrantha poisoned ruminants, associated with epidemiological evidence suggested the diagnosis.Trema micrantha poisoning should be evaluated as a possible cause in the diagnosis of equine hepatopathy and occasional secondary encephalopathy.

Detection of Streptococcus pneumoniae antigen by a rapid immunochromatographic assay in urine samples.

STUDY OBJECTIVES: Evaluation of a newly available rapid (15 min) immunochromatographic membrane test (ICT) to detect Streptococcus pneumoniae in urine samples, in order to assess its utility in the diagnosis of bacteremic and nonbacteremic pneumococcal pneumonia. DESIGN: Retrospective study. SETTING: We studied urine samples from 51 patients with bacteremic and nonbacteremic pneumonia due to S pneumoniae diagnosed by blood culture and pneumococcal polysaccharide capsular antigen detection by counterimmunoelectrophoresis in urine samples, 16 patients with probable pneumococcal pneumonia, 71 patients with nonpneumococcal pneumonia, and 16 patients with pneumonia but no pathogen identified. Urine samples were collected and frozen at - 20 degrees C until used. The ICT test was performed following the instructions of the manufacturer. MEASUREMENTS AND RESULTS: S. pneumoniae antigen was detected in 41 of 51 patients with pneumococcal pneumonia (80.4%); results were positive in 23 of 28 bacteremic cases (82.1%) and in 18 of 23 nonbacteremic cases (78.3%). From patients with a diagnosis of presumptive pneumococcal pneumonia, antigen was detected in seven urine samples (43.7%) and also in one case of the 16 patients with pneumonia but no pathogen identified. The specificity of the ICT test was 97.2%. CONCLUSION: The ICT assay is a valuable tool for the diagnosis of pneumococcal pneumonia, especially for the nonbacteremic cases.

Assessment of a new test to detect Legionella urinary antigen for the diagnosis of Legionnaires' Disease.

Given that the rate of mortality by Legionella pneumonia increases in incorrectly treated patients, rapid diagnosis and early antibiotic treatment are needed. We have assessed the performance of a new enzyme immunoassay (EIA) test (Bartels Inc. Trinity Biotech Company, Wicklow, Ireland) to detect Legionella pneumophila antigen in urine comparing it to Binax EIA (Binax, Portland, Maine). We also evaluated the capability of both EIAs to detect extracted soluble antigens of Legionella strains. Using nonconcentrated urine samples (NCU) the sensitivity of Bartels EIA was 74.1% (66/89) and the sensitivity of Binax EIA was 51.7% (46/89). The sensitivity of both EIA tests were 91.5% (54/59) using concentrated urine samples (CU). Specificity of both EIA tests was 100% in NCU and CU. Bartels EIA was able to detect all serogroup L. pneumophila antigens, achieving a higher sensitivity in the case of L. pneumophila serogroup 1 soluble antigen. The new EIA was found to be a useful test for the rapid diagnosis of Legionella pneumonia, being a better alternative to the Binax EIA if NCU is used.

Longitudinal analysis of fibroblast growth factor expression after transplantation and association with severity of cardiac allograft vasculopathy.

BACKGROUND: Vascular smooth muscle cell growth factors are postulated to contribute to cardiac allograft vasculopathy (CAV). Few data quantitatively address the timing, location, or stimuli for growth factor expression and relationship to CAV. METHODS AND RESULTS: Acidic fibroblast growth factor (aFGF) mRNA expression was determined in serial endomyocardial biopsies during the first year after transplantation. Patients with high levels of aFGF mRNA and elevations after the early posttransplant period had significantly more severe CAV than patients with low aFGF and no late elevations. CONCLUSIONS: Parenchymal aFGF expression varies between patients and in the same patient over time and correlates with development of CAV.

Evaluation of a rapid immunochromatographic assay for the detection of Legionella antigen in urine samples.

A new immunochromatographic membrane assay for detecting Legionella pneumophila serogroup 1 antigen in urine samples (Binax Now Legionella Urinary Antigen Test; Binax, USA) was evaluated. Its sensitivity, specificity and level of agreement with the Binax enzyme immunoassay were compared using nonconcentrated and concentrated urine samples. The overall agreement between the two tests was 98.1%; the specificity of both was 100%. The sensitivity of the immunochromatographic assay was 55.5% in nonconcentrated urine and 97.2% in concentrated urine in comparison with the enzyme immunoassay, using concentrated urine as the reference test. This immunochromatographic assay screens successfully for Legionella pneumophila serogroup 1 soluble antigen in concentrated urine samples.

Comparison of the Binax Legionella urinary antigen enzyme immunoassay (EIA) with the Biotest Legionella Urin antigen EIA for detection of Legionella antigen in both concentrated and nonconcentrated urine samples.

We evaluated a newly commercial enzyme immunoassay (EIA) (Biotest Legionella Urin Antigen EIA; Biotest AG, Dreieich, Germany) for detection of antigens of all Legionella pneumophila serogroups with a relatively wide spectrum of cross-reactivity as well as antigens of other Legionella spp. by comparing its sensitivity and specificity with those of an EIA for detection of L. pneumophila serogroup 1 antigen (Legionella urinary antigen EIA; Binax, Portland, Maine). Both tests were performed with both concentrated and nonconcentrated urine samples. We also evaluated the capabilities of both EIAs to detect extracted soluble antigens of American Type Culture Collection (ATCC) Legionella strains (L. pneumophila serogroups 1 to 14, L. bozemanii, and L. longbeachae). The sensitivity of the Biotest EIA was 66.66% in nonconcentrated urine and 86.66% in concentrated urine. The sensitivity of the Binax EIA was 63.76% and 88.88% in nonconcentrated and concentrated urine, respectively. The specificity was 100% in nonconcentrated and concentrated urine for both assays. The Binax EIA and Biotest EIA detected extracted soluble antigens of L. pneumophila serogroups 1 to 14 and L. bozemanii ATCC strains. The cross-reactions observed with the Binax EIA were probably due to common epitopes directly related to lipopolysaccharide. Further studies are required to determine the usefulness of the Binax EIA for detection of urinary antigens from Legionella species and serogroups other than L. pneumophila serogroup 1. The Biotest EIA proved to be as rapid, sensitive, and specific as the Binax EIA for the diagnosis of legionellosis. Concentration of antigen present in urine increased the sensitivities of both techniques with no reduction in specificity.

Gram-scale purification of phosphorothioate oligonucleotides using ion-exchange displacement chromatography.

The purification of oligonucleotides by ion-exchange displacement chromatography is demonstrated on the gram-scale. Using a 50 mmD x 100 mmL (203 ml) column operated in the displacement mode, 1.2 g of a 24mer phosphorothioate oligonucleotide was purified. Product yield for this separation was 70% (780 mg) at a purity of 96.4% and the mass balance recovery of all oligonucleotide was 97.5%. The displacement purification of four additional phosphorothioate oligonucleotides ranging in length from 18 to 25 bases is also demonstrated on the semi-preparative (10-50 mg) scale. All of these oligonucleotides were purified using similar displacement conditions and typical results were 60% yield at 96% purity. The displacement portion of these separations required <15 min and total cycle time including equilibration, feed loading and regeneration can be performed in under 30 min. These results seem to indicate that displacement chromatography may be amenable to generalizations in separation protocol that would greatly reduce the effort required to obtain an optimized purification scheme for moderately long oligonucleotides.

Rapid screening with indirect immunotoxin for monoclonal antibodies against human small cell lung cancer.

For the first time, a screening procedure for antitumor monoclonal antibodies (MOABs) has been developed in which the ability of MOABs to mediate the indirect action of another immunotoxin is the primary criterion for selection of hybridomas for expansion and cloning. Use of the indirect immunotoxin makes it possible to screen MOABs for cytotoxic potential without the necessity of covalently coupling toxin to each individual MOAB. Hybridomas derived from spleens of immunized mice were screened for the synthesis of monoclonal antibodies able to participate in the delivery of a pharmacologically active, indirect immunotoxin conjugate to H69 lung cancer cells. The indirect immunotoxin conjugate was goat anti-mouse immunoglobulin disulfide linked to pokeweed antiviral protein. There was no correlation between the results of the screening with the indirect immunotoxin and an enzyme-linked immunosorbent assay screen for binding of MOAB to tumor cell membranes. An indirect immunotoxin prepared from Fab' fragments of goat anti-mouse immunoglobulin was also effective as an indirect immunotoxin conjugate. Each screening of more than 300 hybridomas was performed in 3 days. The indirect immunotoxin screen detected antitumor MOABs which were not detected by the conventional enzyme-linked immunosorbent assay method. A MOAB selected by the indirect immunotoxin screen was conjugated to pokeweed antiviral protein; the conjugate mediated immunocytotoxicity in a standard direct toxicity assay.

La suprarrenalectomía asociada a la gangliectomía en el tratamiento de la tromboangeítis obliterante

Se presentan catorcer casos de troboangiitis obliterante tratados por gangliectomía asociada a la suprarrenalectomía en un solo tiempo. En un 86 porciento de los casos se obtuvo éxito en el tratamiento, acorde con su influencia sobre el dolor y las lesiones. Se analiza su influencia sobre la claudicación y sobre las crisis de isquemia en casos evaluados a los tres años de la operación. se enfatiza la vía empleada como la mejor para la operación combinada. No hemos encontrado en nuestra literatura nacional ninguna referencia del tratamiento de la tromboangeítis obliterante por la suprarrenalectomía asociada a la gangliectomía (AU)

La flebografía, su valor en el tratamiento de las úlceras de estasis recidivantes

Se presenta un método de flebografía para el estudio de las úlceras de estasis recidivantes. Se informa de los resultados obtenidos (AU)

Tromboendarteriectomía con parche venoso en el tratamiento de la arterioesclerosis obliterante segmentaria

Se presentan 12 casos de arterioesclerosis obliterante segmentaria tratados por medio de la tromboendarteriectomía con parche venoso. Hubo 4 fallos con amputaciones y una muerte. Se precisan algunos factores de técnica y se discute la superioridad de este procedimiento sobre otras técnicas. Posteriormente a la presentación de este trabajo hemos realizado 5 tromboendarteriectomías con parche venoso más, en las que no ha habido muerte ni fallos. Uno de los casos hizo a los 2 meses una obstrucción proximal al parche, en el sector ilíaco. Estos resultados nos obligan a considerar la tromboendarteriectomía en parche venoso como el proceder de elección para la cirugía reparadora de la arterioesclerosis obliterante de los miembros (AU)

Injertos plásticos arteriales (Dacrón) en el tratamiento de las oclusiones arteriales

Se presentan 22 pacientes con oclusiones vasculares tratados por medio del injerto plástico de Dacrón. El postoperatorio se extiende desde 2 meses hasta 2 años. El resultado en las heridas vasculares muestranuna gran proporción de fallos 5 de 7 casos, siendo abandonado el uso del mismo en dicha patología. En las oclusiones arterioescleróticas los mejores resultados se obtienen en el sector aortoilíaco, 3 fallos en 8 casos; en el sector fémoropoplíteo su combinación con la tromboendarteriectomía aún en cosas de gangrena incipiente es de utilidad (AU)