Physicochemical Evaluation of Acid–Base Disorders After Liver Transplantation and the Contribution From Administered Fluids

Objectives

To analyze the mechanism of acid–base disorders in liver transplant recipients and to examine the relationship between these disorders and the fluids administered during surgery.

Methods

This prospective study in a university-affiliated hospital intensive care unit (ICU) included 52 patients admitted to the ICU from December 2009 to January 2011. We examined the contributions of inorganic ion differences, lactate, unmeasured anions, phosphate, and albumin to metabolic acidosis. In addition to laboratory variables, we collected demographic and clinical data.

Results

Metabolic acidosis (standard base excess ≤ −2.0 mmol/L) was identified in 37 (71.2%) patients during the immediate postoperative period. The inorganic ion difference was the main determinant of acidosis, accounting for −6.17 mEq/L of acidifying effect. The acidemia was attenuated mainly by the alkalinizing effect of albumin reduction, which contributed +6.03 mEq/L. There was an inverse proportional relationship between the quantity of saline solution used during surgery and the inorganic ion difference during the immediate postoperative period.

Conclusions

Hyperchloremia is the primary contributor to metabolic acidosis in liver transplant recipients. Possibly the use of chloride-rich solutions increases the incidence of this disorder.     

Ultrasonographic screening for thyroid cancer in siblings of patients with apparently sporadic papillary carcinoma

Background: Epidemiological studies have shown a higher risk of thyroid cancer among individuals who have a relative with papillary thyroid cancer (PTC) compared to those without a family history. This study evaluated the prevalence of thyroid cancer among subjects with only one first-degree relative (sibling) with PTC who had no palpable nodules, factors predictive of this malignancy, and the characteristics of tumors discovered during ultrasonographic screening. Methods: A total of 757 siblings of 447 patients with apparently sporadic PTC were examined. Nodules were palpable in 34 subjects (excluded). The 723 individuals without palpable abnormalities were submitted to thyroid ultrasonography and comprised the study group. The control group, consisting of 241 volunteers without a family history of thyroid cancer matched for gender and age to the study group, was also submitted to thyroid ultrasonography. All nodules ≥5?mm were examined by fine-needle aspiration cytology. Subjects with benign cytology were not submitted to surgery, whereas the subjects having malignant, suspicious for a malignancy, indeterminate, or inadequate cytology were referred for thyroidectomy. Results: Ultrasonography detected nodules in 303 (41.9%) study subjects. PTC was observed in 5.94% of the 723 subjects studied (8% women and 3.75% men, p=0.017) and in 14.2% of the 303 subjects with nonpalpable nodular disease. In the control group, 80 (33.2%) of the volunteers had nodules. PTC was observed in 1.2% of them and in 3.8% of those with nodular disease. In addition, 7.17% of the 447 patients had siblings with PTC detected only by ultrasonography. Multicentricity of the tumor was the main predictor of the presence of malignancy in siblings of patients with PTC. Twenty-two subjects (3% of those screened) had tumors that were not intrathyroid microcarcinomas (whereas all three tumors detected in controls were intrathyroid microcarcinomas). Screening permitted an earlier diagnosis of the disease when compared to siblings with a spontaneous diagnosis. Conclusions: The present results favor ultrasonographic screening of first-degree relatives of patients with apparently sporadic multicentric PTC, especially among women.     

C.E.R.A. maintains stable hemoglobin in Latin American patients on dialysis

Background

C.E.R.A. is a continuous erythropoietin receptor activator with characteristics that permit a once-monthly schedule of administration for the maintenance treatment for chronic kidney disease (CKD) patients. The main objective of this study was to assess the maintenance of Hb concentration with once-monthly intravenous and/or subcutaneous C.E.R.A. therapy in Latin American dialysis patients with chronic renal anemia previously treated with epoetin alfa s.c or i.v 1–3 times per week.

Methods

This was a single-arm, open-label, multicenter, 32-week study of anemic patients with CKD previously treated with epoetin alfa sc or iv 1–3 times per week. After a 4-week screening period, during which mean Hb levels were maintained between 10.5 and 12.5 g/dL on their previous erythropoiesis stimulating agent, eligible patients entered a 16-week C.E.R.A. dose titration period followed by a 4-week efficacy evaluation period (EEP) and a 28-week safety follow-up. The starting dose of C.E.R.A. was based on the previous dose of epoetin alfa. Doses of C.E.R.A. were then adjusted to maintain Hb levels within ±1.0 g/dL of the reference concentration and between 10.5 and 12.5 g/dL. The Hb reference concentration was defined as the mean of all Hb levels during screening. The primary end point was the proportion of patients maintaining a mean Hb concentration (g/dL) within ±1 g/dL of their reference Hb and between 10.5 and 12.5 g/dL during the EEP.

Results

A total of 163 patients from 27 centers in Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, Peru, Uruguay, and Venezuela entered the treatment period and 102 completed the prescribed course of C.E.R.A. Forty-five patients (43.7 %) maintained a mean Hb concentration within ±1 g/dL of their reference Hb value and between 10.5 and 12.5 g/dL during the EEP. The median monthly dose remained constant at 120 μg during the titration period and during the EEP. On the average, there were only 2.3 dose changes per patient in 28 weeks of treatment, covering 7 C.E.R.A. scheduled administrations. 53 % of all dose changes were dose decreases, 47 % increases. A total of 10 AEs and 4 SAEs were considered to be related to the study treatment.

Conclusions

Once-monthly C.E.R.A. treatment effectively maintains stable Hb concentrations in patients with chronic renal anemia undergoing dialysis with a good safety and tolerability profile.     

Effects of unilateral stereotactic posterior striatotomy on harmaline‐induced tremor in rats

Although long known and the most prevalent movement disorder, pathophysiology of essential tremor (ET) remains controversial. The most accepted hypothesis is that it is caused by a dysfunction of the olivocerebellar system. Vilela Filho et al. [2001; Stereotact Funct Neurosurg 77:149–150], however, reported a patient with unilateral hand ET that was completely relieved after a stroke restricted to the contralateral posterior putamen and suggested that ET could be the clinical manifestation of posterior putamen hyperactivity. The present study was designed to evaluate this hypothesis in the most often used model of ET, harmaline‐induced tremor in rats. Fifty‐four male Wistar rats were randomly distributed into three groups: experimental (EG), surgical control (SCG), and pharmacological control (PCG) groups. EG animals underwent stereotactic unilateral posterior striatotomy. SCG rats underwent sham lesion at the same target. PCG served exclusively as controls for harmaline effects. All animals received, postoperatively, intraperitoneal harmaline, and the induced tremor was video‐recorded for later evaluation by a blind observer. Thirteen animals were excluded from the study. Limb tremor was reduced ipsilaterally to the operation in 20 of 21 rats of EG and in two of nine of SCG, being asymmetric in one of 10 of PCG rats. Comparisons between EG × SCG and EG × PCG were statistically significant, but not between SCG × PCG. Limb tremor reduction was greater in anterior than in posterior paws. Lateral lesions yielded better results than medial lesions. These results suggest that the posterior striatum is involved with harmaline‐induced tremor in rats and support the hypothesis presented. © 2013 Wiley Periodicals, Inc.     

Neuroprotective Effect of Physical Exercise in a Mouse Model of Alzheimer’s Disease Induced by β-Amyloid1–40 Peptide

This study was designed to investigate the potential neuroprotective effect of exercise in a mouse model of Alzheimer’s disease (AD) induced by intracerebroventricular (i.c.v.) injection of beta-amyloid_1–40 (Aβ_1–40) peptide. For this aim, male Swiss Albino mice were submitted to swimming training (ST) with progressive increase in intensity and duration for 8 weeks before Aβ_1–40 administration (400 pmol/animal; 3 μl/site, i.c.v. route). The cognitive behavioral, oxidative stress, and neuroinflammatory markers in hippocampus and prefrontal cortex of mice were assessed 7 days after Aβ_1–40 administration. Our results demonstrated that ST was effective in preventing impairment in short- and long-term memories in the object recognition test. ST attenuated the increased levels of reactive species and decreased non-protein thiol levels in hippocampus and prefrontal cortex induced by Aβ_1–40. Also, Aβ_1–40 inhibited superoxide dismutase activity and increased glutathione peroxidase, glutathione reductase, and glutathione S-transferase activities in hippocampus and prefrontal cortex—alterations that were mitigated by ST. In addition, ST was effective against the increase of tumor necrosis factor-alpha and interleukin-1 beta levels and the decrease of interleukin-10 levels in hippocampus and prefrontal cortex. This study confirmed the hypothesis that exercise is able to protect against some mechanisms of Aβ_1–40-induced neurotoxicity. In conclusion, we suggest that exercise can prevent the cognitive decline, oxidative stress, and neuroinflammation induced by Aβ_1–40 in mice supporting the hypothesis that exercise can be used as a non-pharmacological tool to reduce the symptoms of AD.     

Acute cellular rejection and HLA mismatch in heart transplantation: insights from a developing country

The notable evolution of heart transplant (HTX) has paralleled the capacity of diagnosing rejection and, consequently, initiating timely treatment. Acute cellular rejection, diagnosed by endomyocardial biopsy, is the most frequent in the first 6 months after HTX. HLA matching is not routinely performed in HTX due to the absence of consensus regarding its usefulness. However, the use of HLA typing might be underscored if it could predict an increased risk of rejection. Therefore, the aim of this study was to evaluate, at a public cardiology center in Brazil, the association between HLA mismatches and the incidence of acute cellular rejection in the first 6 months after HTX. Data were obtained from hospital records and from the National Transplant System. Overall, there was no association between the number of HLA mismatches and the frequency of acute cellular rejection, but there was a tendency toward a higher incidence of rejection with HLA‐DR incompatibility.     

Serum nitrate and NOx levels in preeclampsia are higher than in normal pregnancy

Objectives: To compare nitric oxide (NO) serum levels in women with and without preeclampsia. Methods: 106 women were classified into preeclampsia group (n = 40) and normotensive group (n = 66). NO content was measured in the serum. Clinical and laboratorial data were recorded for comparison. Results: Preeclampsia presented a significant increase in nitrate and NOx levels compared to the control group. Uric acid, gestational age, systolic and diastolic blood pressure, and creatinine showed correlation with nitrates and NOx. Conclusion: Increase of NO was observed in preeclampsia women. Failure in the mechanism of action, dependent on cyclic GMP, may justify this finding.