Effect of Weight Loss on Aerobic Capacity in Patients with Severe Obesity Before and After Bariatric Surgery

Severe obesity has been associated with adverse effects on physical capacity. In a prospective study, the aerobic capacity of severely obese patients was measured in order to observe the physiological response to weight loss from bariatric surgery. Sixty-five consecutive patients (40.4 +/- 8.4 years old; 93.8% female; body mass index = 49.4 +/- 5.4 kg/m(2)) were evaluated before bariatric surgery and then 6 and 12 months after surgery. Aerobic capacity was assessed with a scientific treadmill to measure maximal oxygen consumption (VO(2max)), heart rate, blood pressure, time on the treadmill, and distance walked (modified Bruce test). For the three observational periods, VO(2max) was 25.4 +/- 9.3, 29.8 +/- 8.1, and 36.7 +/- 8.3 ml/kg/min; time on the treadmill was 5.4 +/- 1.4, 6.4 +/- 1.6, and 8.8 +/- 1.0 min; and distance walked was 401.8 +/- 139.1, 513.4 +/- 159.9, and 690.5 +/- 76.2 m. For these variables, significant results (p = 0.0000) were observed for the two postoperative periods in relation to the preoperative period. Severely obese individuals increased their aerobic capacity after successful bariatric surgery. The data also suggests that a positive and progressive relationship between weight loss and improvement in fitness as a moderate loss of weight 6 months after surgery already showed some benefit and an additional reduction in weight was associated with a better performance in the aerobic capacity tests at the 12-month follow-up.

Pro- and Anti-inflammatory Cytokines in Steatosis and Steatohepatitis

Fatty liver disease is a problem in both bariatric patients and in patients with moderate obesity. Tumor necrosis factor (TNF)-alpha has been frequently measured in nonalcoholic steatohepatitis (NASH) with or without diabetes, but less is known about interleukin (IL)-6 and IL-10. Moderately obese patients (n = 80) with histologically proven steatosis (n = 29) and NASH (n = 51) were recruited. Serum levels of cytokines were documented along with clinical information. The aim was to identify the correlates of such biomolecules in a stable population. Diabetes tended to be more associated with NASH (52.5% instead of 41.4%, P = 0.015), with no difference of age, gender, or body mass index regarding steatosis. For the entire population, cytokine changes were not significant, including TNF-alpha and IL-6. In diabetics only, all markers tended to diminish with NASH, especially IL-10 (P = 0.000). IL-10 correlated with homeostatic model assessment index (P = 0.000) and other variables of glucose homeostasis in diabetes, thus representing a major marker of the disease. (1) Generally inconsistent changes in pro- and anti-inflammatory cytokines occurred when NASH was globally compared to steatosis. (2) In contrast, downregulation of IL-6 and IL-10 was perceived in diabetics with NASH. (3) Arterial hypertension did not play a role in these circumstances. (4) IL-10 maintained strong correlations with glucose metabolism indices. (5) TNF-alpha could not be incriminated for progressive liver damage, as values failed to increase in NASH. (6) Investigations of IL-10 and other counterregulatory cytokines are lacking in this context and deserve further studies.

Long-term nutritional assessment of patients with severe short bowel syndrome managed with home enteral nutrition and oral intake

Background: Parenteral nutrition (PN) is used to control the nutritional state after severe intestinal resections. Whenever possible, enteral nutrition (EN) is used to promote intestinal rehabilitation and reduce PN dependency. Our aim is to verify whether EN + oral intake (01) in severe short bowel syndrome (SBS) surgical adult patients can maintain adequate nutritional status in the long term. Methods: This longitudinal retrospective study included 10 patients followed for 7 post-operative years. Body mass index (BMI), percentage of involuntary loss of usual body weight (UWL), free fat mass (FFM), and fat mass (FM) composition assessed by bioelectric impedance, and laboratory tests were evaluated at 6, 12, 24, 36, 48, 60, 72, and 84 months after surgery. Energy and protein offered in HPN and at long term by HEN+ oral intake (01), was evaluated at the same periods. The statistical model of generalized estimating equations with p <0,05 was used. Results: With long term EN + 01 there was a progressive increase in the UWL, a decrease in BMI, FFM, and FM (p < 0,05). PN weaning was possible in eight patients. Infection due to central venous catheter (CVC) contamination was the most common complication (1.2 episodes CVC/patient/year). There was an increase in energy and protein intake supply provided by HEN+OI (p <0.05). All patients survived for at least 2 years, seven for 5 years and six for 7 years of follow-up. Conclusions: In the long term SBS surgical adult patients fed with HEN+OI couldn`t maintain adequate nutritional status with loss of FM and FFM. (Nutr Hosp. 2011;26:834-842) DOI:10.3305/nh.2011.26.4.5153

Experimental multivisceral xenotransplantation

Background: Organ shortage impairs the proposition of multivisceral transplantation to treat multiple organ failure. Interspecies (xeno) transplantation is a valid solution for organ shortage; however, suitable models of this advance are lacking. We describe an effective model of multivisceral xenotransplantation to study hyperacute rejection. Methods: Under general anesthesia, we in block recovered the distal esophagus, stomach, small bowel, colon, liver, pancreas, spleen, and kidneys from donors and implanted heterotopically in the lower abdomen of recipients. Animals were divided into four groups: I-canine donor, swine recipient (n = 6); II - swine donor, canine recipient (n = 5); III-canine donor, canine recipient (n = 4); and IV-swine donor, swine recipient (n = 5). Groups I and 11 comprised experimental (xenotransplantation) and III and IV control groups (allotransplantation). During the experiment, we appraised recipient evolution and graft modification by sequential biopsy up to 3 h. At this time, we killed animals for autopsy (experimental end point). Results: We accomplished all experiments successfully. Every grafts attained customary appearance and convenient urine output immediately after unclamp. Around 15 min after reperfusion, xenografts achieved signs of progressive hyperacute rejection and absence of urine output. At the end of experiments we observed moderate to severe hyperacute rejection at small bowel, colon, mesenteric lymph node, liver, spleen, pancreas, and kidney, while stomach and esophagus achieved mild lesions. In contrast, allograft achieved normal or minimum ischemia/reperfusion injury and constant urine output. Conclusion: The present procedure assembles a simple and effective model to study multivisceral xenotransplantation and may ultimately spread researches toward hyperacute rejection.

Major histocompatibility complex (MHC) class II-positive dendritic cells in the rat iris - In situ development from MHC class II-negative precursors

Purpose. To examine the postnatal development of major histocompatibility complex (MHC) class II-positive dendritic cells (DC) in the iris of the normal rat eye. Methods. Single-and double-color immunomorphologic studies were performed on whole mounts prepared from rat iris taken at selected postnatal ages (2 to 3 days to 78 weeks). Immunopositive cells were enumerated, using a quantitative light microscope, and MHC class II expression on individual cells was assessed by microdensitometric analysis. Results. Major histocompatibility class II-positive DCs in the iris developed in an age-dependent manner and reached adult-equivalent density and structure at approximately 10 weeks of age, considerably later than previously described in other DC populations in the rat. In contrast, the anti-rat DC monoclonal antibody OX62 revealed a population of cells present at adult-equivalent levels as early as 3 weeks after birth. Dual-color immunostaining and microdensitometric analysis demonstrated that during postnatal growth, development of the network of MHC class II-positive DCs was a consequence of the progressive increase in expression of MHC class II antigen by OX62-positive cells. Conclusions. During postnatal growth, the DC population of the iris develops initially as an OX62-positive-MHC class II-negative population, which then develops increasing MHC class II expression in situ and finally resembles classic DC populations in other tissue sites. Maturation of the iris DC population is temporally delayed compared with time to maturation in other tissue sites in the rat.

Evaluation of interventions to reduce catheter-associated bloodstream infection: Continuous tailored education versus one basic lecture

Background: This study evaluated the impact of 2 models of educational intervention on rates of central venous catheter-associated bloodstream infections (CVC-BSIs). Methods: This was a prospective observational study conducted between January 2005 and June 2007 in 2 medical intensive care units (designated ICU A and ICU B) in a large teaching hospital. The study was divided into in 3 periods: baseline (only rates were evaluated), preintervention (questionnaire to evaluate knowledge of health care workers [HCWs] and observation of CVC care in both ICUs), and intervention (in ICU A, tailored, continuous intervention; in ICU B, a single lecture). The preintervention and intervention periods for each ICU were compared. Results: During the preintervention period, 940 CVC-days were evaluated in ICUA and 843 CVC-days were evaluated in ICU B. During the intervention period, 2175 CVC-days were evaluated in ICUA and 1694 CVC-days were evaluated in ICU B. Questions regarding CVC insertion, disinfection during catheter manipulation, and use of an alcohol-based product during dressing application were answered correctly by 70%-100% HCWs. Nevertheless, HCWs` adherence to these practices in the preintervention period was low for CVC handling and dressing, hand hygiene (6%-35%), and catheter hub disinfection (45%-68%). During the intervention period, HCWs` adherence to hand hygiene was 48%-98%, and adherence to hub disinfection was 82%-97%. CVC-BSI rates declined in both units. In ICUA, this decrease was progressive and sustained, from 12CVC-BSIs/1000 CVC-days at baseline to 0 after 9 months. In ICU B, the rate initially dropped from 16.2 to 0 CVC-BSIs/1000 CVC-days, but then increased to 13.7 CVC-BSIs/1000 CVC-days. Conclusion: Personal customized, continuous intervention seems to develop a ""culture of prevention"" and is more effective than single intervention, leading to a sustained reduction of infection rates.

DNA damage and repair in leukocytes of melanoma patients exposed in vitro to cisplatin

Resistance to chemotherapeutic drugs can be an obstacle to a successful treatment of cancer patients in part associated with individual response and differences in the DNA repair system. The Comet assay is an informative test to investigate DNA damage and repair in cells in response to a variety of DNA-damaging agents, including chemotherapeutic drugs. The aim of this study was to assess leukocytes damage after in-vitro cisplatin treatment and DNA repair action using the Comet assay in 20 patients with melanoma and 20 cancer-free individuals. Leukocytes` DNA damage before and after cisplatin treatment, in three different concentrations, was analyzed. The DNA repair capability was investigated after 1-5 h of in-vitro cells growing without cisplatin. The Comet score of the patients` basal DNA damage was higher than that observed in controls, but the difference was not statistically significant (P=0.85). Although both groups had similar Comet scores to all cisplatin concentrations tested and the DNA repair times, the basal DNA damage (P < 0.001) and cisplatin damages (P < 0.005) were statistically lower than the different repair times investigated. Considering the progressive increase in the Comet score due to repair time, the negative results here observed could be associated with the reduced cell culture incubation that should be better evaluated. Considering the mutagenic action of cisplatin on tumor cells and the importance of individual DNA repair mechanisms in the chemotherapeutic melanoma treatment, the peripheral leukocytes could be particularly useful as a tool for DNA repair response identified by the Comet assay. Melanoma Res 21:99-105 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Molecular basis of infantile reversible cytochrome c oxidase deficiency myopathy

Childhood-onset mitochondrial encephalomyopathies are usually severe, relentlessly progressive conditions that have a fatal outcome. However, a puzzling infantile disorder, long known as `benign cytochrome c oxidase deficiency myopathy` is an exception because it shows spontaneous recovery if infants survive the first months of life. Current investigations cannot distinguish those with a good prognosis from those with terminal disease, making it very difficult to decide when to continue intensive supportive care. Here we define the principal molecular basis of the disorder by identifying a maternally inherited, homoplasmic m.14674T > C mt-tRNA(Glu) mutation in 17 patients from 12 families. Our results provide functional evidence for the pathogenicity of the mutation and show that tissue-specific mechanisms downstream of tRNA(Glu) may explain the spontaneous recovery. This study provides the rationale for a simple genetic test to identify infants with mitochondrial myopathy and good prognosis.

Early motor and electrophysiological changes in transgenic mouse model of amyotrophic lateral sclerosis and gender differences on clinical outcome

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disorder affecting motoneurons and the SOD1(G93A) transgenic mice are widely employed to study disease physiopathology and therapeutic strategies. Despite the cellular and biochemical evidences of an early motor system dysfunction, the conventional behavioral tests do not detect early motor impairments in SOD1 mouse model. We evaluated early changes in motor behavior of ALS mice by doing the analyses of tail elevation, footprint, automatic recording of motor activities by means of an infrared motion sensor activity system and electrophysiological measurements in male and female wild-type (WT) and SOD1(G93A) mice from postnatal day (P) 20 up to endpoint. The classical evaluations of mortality, weight loss, tremor, rotometer, hanging wire and inclined plane were also employed. There was a late onset (after P90) of the impairments of classical parameters and the outcome varied between genders of ALS mice, being tremor, cumulative survival, weight loss and neurological score about 10 days earlier in male than female ALS mice and also about 20 days earlier in ALS males regarding rotarod and hanging wire performances. While diminution of hindpaw base was 10 days earlier in ALS males (P110) compared to females, the steep length decreased 40 days earlier in ALS females (P60) than ALS males. The automatic analysis of motor impairments showed substantial late changes (after P90) of motility and locomotion in the ALS females, but not in the ALS males. It was surprising that the scores of tail elevation were already decreased in ALS males and females by P40, reaching the minimal values at the endpoint. The electrophysiological analyses showed early changes of measures in the ALS mouse sciatic nerve, i.e., decreased values of amplitude (P40) and nerve conduction velocity (P20), and also an increased latency (P20) reaching maximal level of impairments at the late disease phase. The early changes were not accompanied by reductions of neuronal protein markers of neurofilament 200 and ChAT in the ventral part of the lumbar spinal cord of P20 and P60 ALS mice by means of Western blot technique, despite remarkable decreases of those protein levels in P120 ALS mice. In conclusion, early changes of motor behavior and electrophysiological parameters in ALS mouse model must be taken into attention in the analyses of disease mechanisms and therapeutic effects. (C) 2011 Published by Elsevier B.V.

Cor pulmonale in a patient with Brown-Vialetto-Van Laere syndrome: A case report

Brown-Vialetto-Van Laere syndrome (BVVLS) is a rare neurological disease characterized by sensorineural hearing loss and multiple cranial nerve palsies, usually involving the VIIth and IXth to XIIth cranial nerves. We describe the clinical and pathological features of a 33-year-old woman with BVVLS. The patient developed progressive exertional dyspnea, with clinical and laboratory findings of right-sided heart failure and pulmonary hypertension. She developed status epilepticus in the setting of cardiac deterioration and respiratory infection, and died of cardiogenic and septic shock. Autopsy disclosed bilateral neuronal loss and gliosis in the inferior colliculi, locus coeruleus and facial and vestibular nuclei. Cor pulmonale is a complication of hypoventilation-induced hypoxia and hypercapnia and had not yet been reported in BVVLS. (C) 2010 Elsevier B.V. All rights reserved.

Evaluation of retinal nerve fiber layer thickness measurements using optical coherence tomography in patients with tobacco-alcohol-induced toxic optic neuropathy

Three patients with progressive visual loss, chronic alcoholism and tabagism were submitted to a complete neuro-ophthalmic examination and to retinal nerve fiber layer (RNFL) measurements using optical coherence tomography (OCT) scanning. Two patients showed marked RNFL loss in the temporal sector of the optic disc. However, a third patient presented RNFL measurements within or above normal limits, based on the Stratus-OCT normative database. Such findings may be due to possible RNFL edema similar to the one that may occur in the acute phase of toxic optic neuropathies. Stratus-OCT was able to detect RNFL loss in the papillomacular bundle of patients with tobacco-alcohol-induced toxic optic neuropathy. However, interpretation must be careful when OCT does not show abnormality in order to prevent diagnostic confusion, since overestimation of RNFL thickness measurements is possible in such cases.

Impact of Atypical Retardation Patterns on Detection of Glaucoma Progression using the GDx with Variable Corneal Compensation

PURPOSE: To evaluate the impact of atypical retardation patterns (ARP) on detection of progressive retinal nerve fiber layer (RNFL) loss using scanning laser polarimetry with variable corneal compensation (VCC). DESIGN: Observational cohort study. METHODS: The study included 377 eyes of 221 patients with a median follow-up of 4.0 years. Images were obtained annually with the GDx VCC (Carl Zeiss Med, itec Inc, Dublin, California, USA), along with optic disc stereophotographs and standard automated perimetry (SAP) visual fields. Progression was determined by the Guided Progression Analysis software for SAP and by masked assessment of stereophotographs by expert graders. The typical scan score (TSS) was used to quantify the presence of ARPs on GDx VCC images. Random coefficients models were used to evaluate the relationship between ARP and RNFL thickness measurements over time. RESULTS: Thirty-eight eyes (10%) showed progression over time on visual fields, stereophotographs, or both. Changes in TSS scores from baseline were significantly associated with changes in RNFL thickness measurements in both progressing and nonprogressing eyes. Each I unit increase in TSS score was associated with a 0.19-mu m decrease in RNFL thickness measurement (P < .001) over time. CONCLUSIONS: ARPs had a significant effect on detection of progressive RNFL loss with the GDx VCC. Eyes with large amounts of atypical patterns, great fluctuations on these patterns over time, or both may show changes in measurements that can appear falsely as glaucomatous progression or can mask true changes in the RNFL. (Am J Ophthalmol 2009;148:155-163. (C) 2009 by Elsevier Inc. All rights reserved.)

Lead Poisoning by Intradiscal Firearm Bullet A Case Report

Study Design. The report of a rare case of lead poisoning by an intradiscal firearm bullet is presented. Objective. To describe and discuss the clinical and radiologic features (by computed tomography and magnetic resonance imaging) of a gunshot wound in the L2-L3 space which caused lead poisoning 5 years afterwards. Summary of Background Data. Lead poisoning from firearm bullets is rare, but the possibility should be investigated in the case of bullets lodged in the joints. Methods. A 30-year-old man presented to the emergency room with an intense lumbar pain complaint, colic, intestinal constipation, insomnia, and progressive headache for 20 days. He had a history of a gunshot wound 5 years previously, and the bullet was left in situ, in the intravertebral disc between L2 and L3, as confirmed by radiographs, computed tomography, and magnetic resonance imaging. The hypothesis of lead poisoning was confirmed by the laboratory results. Chelation treatment with calcium versenate (disodium ethylenediaminetetraacetate, or CaNa (2) EDTA) was indicated. The patient was admitted and treated once again, before surgical removal of the bullet. Results. After removal of the bullet, the patient had an episode of recurrence, and a new chelation cycle was performed, with complete resolution. Conclusion. Lead poisoning can result in severe clinical disorders that require rapid treatment. In this case, both clinical and surgical treatments led to complete resolution of the symptoms.

Effects of the association zidovudine plus ritonavir on the liver and kidneys of pregnant rats. Morphological and biochemical aspects

Purpose: To evaluate biochemical and morphological effects on rats submitted to three different doses of the association zidovudine and ritonavir administered throughout pregnancy. Methods: Forty pregnant EPM-1 Wistar rats weighing about 200 g were randomly divided into the control group (Ctr = drug vehicle control, n = 10) and three experimental ones which were treated with an oral solution of zidovudine/ritonavir (Exp1 = 10/20 mg/kg bw, n = 10; Exp2 = 30/60 mg/kg bw, n = 10; Exp3 = 90/180 mg/kg bw, n = 10) from `day 0` up to the 20th day of pregnancy. At term (20th day) the rats were anesthetized. Blood and fetal and maternal organ samples (livers and kidneys) were taken for morphological and biochemical analyses. Results: Upon histological examinations fetal livers and kidneys appeared normal. In contrast the maternal samples revealed structural alterations. Maternal kidneys of the three experimental groups exhibited progressive and dose-dependent histological alterations; liver alterations were detected only in Exp3. Blood levels of AST and ALT were not significantly different from the control group but urea and creatinine levels were lower in groups Exp3 and Exp1. Conclusions: The administration of zidovudine plus ritonavir throughout rat pregnancy can cause morphological as well as functional changes in maternal kidneys.

Lack of progression of brain abnormalities in first-episode psychosis: a longitudinal magnetic resonance imaging study

Background. Some neuroimaging studies have supported the hypothesis of progressive brain changes after a first episode of psychosis. We aimed to determine whether (i) first-episode psychosis patients would exhibit more pronounced brain volumetric changes than controls over time and (ii) illness course/treatment would relate to those changes. Method. Longitudinal regional grey matter volume and ventricle : brain ratio differences between 39 patients with first-episode psychosis (including schizophrenia and schizophreniform disorder) and 52 non-psychotic controls enrolled in a population-based case-control study. Results. While there was no longitudinal difference in ventricle : brain ratios between first-episode psychosis subjects and controls, patients exhibited grey matter volume changes, indicating a reversible course in the superior temporal cortex and hippocampus compared with controls. A remitting course was related to reversal of baseline temporal grey matter deficits. Conclusions. Our findings do not support the hypothesis of brain changes indicating a progressive course in the initial phase of psychosis. Rather, some brain volume abnormalities may be reversible, possibly associated with a better illness course.