The effect of two different doses comprising the simultaneous administration of intravenous B-complex vitamins and oral folic acid on serum homocysteine levels in hemodialysis patients

Background: Several regimens using different doses of folic acid (FA) alone or supplemented with B-complex vitamins (BCVs) have been tested for their ability to reduce total homocysteine (tHcy) serum levels in hemodialysis (HD) patients. In the present study, we assessed the effect of two different doses comprising the simultaneous administration of intravenous (IV) BCVs and an oral FA supplementation on serum tHCy levels in HD patients. Patients–methods: In a cohort of 49 patients (31 male, 18 female) undergoing chronic HD treatment for a mean of 40.0±40.7 months, serum concentrations of tHcy, folate and vitamin-B12 (vB12) were determined at the end of three sequential periods as follows: 20 weeks without any BCV and/or FA supplementation (period A), 20 weeks with a dose comprising the simultaneous administration of IV BCVs and an oral supplementation of 5 mg of FA once a week (period B), and 20 weeks with a dose comprising the simultaneous administration of IV BCVs and an oral supplementation of 5 mg of FA thrice a week (period C). An IV dose of BCVs consisting of a 5 mL solution containing vitamin B₁ (250 mg), vitamin B₆ (250 mg) and vitamin B₁₂ (1.5 mg) was administered at the end of hemodialysis. Results: Mean serum tHcy levels were significantly higher at the end of period A relative to levels at the end of periods B and C (35.8±23 μmol/L vs. 22.0±17.6 and 15.0±4.5 μmol/L, respectively; p < 0.000001). Mean serum folate levels and mean serum vB12 levels were significantly lower at the end of period A relative to levels at the end of periods B and C (p < 0.000001). Mean serum tHcy levels were lowest at the end of period C (p < 0.000001 in comparison to periods A and B), and 26 of the 49 HD patients (67.3%) possessed tHcy levels below 16 μmol/L. Conclusions: In HD patients, high doses consisting of the simultaneous administration of IV BCVs and an oral FA supplementation resulted in the efficient reduction of serum tHcy levels.     

Molecular pathogenetics of renal cancer

Recent developments in genetics and molecular biology have led to an increased understanding of the pathobiology of renal cancer. Thorough knowledge of the molecular pathways associated with renal cancer is a prerequisite for novel potential therapeutic interventions. Studies are ongoing to evaluate novel anticancer agents that target specific molecular entities. This article reviews current knowledge on the genetics and molecular pathogenesis of sporadic and inherited forms of renal cancer.     

Skeletal muscle adaptations to interval training in patients with advanced COPD

STUDY OBJECTIVES: To investigate the response to interval exercise (IE) training by looking at changes in morphologic and biochemical characteristics of the vastus lateralis muscle, and to compare these changes to those incurred after constant-load exercise (CLE) training. DESIGN: Randomized, controlled, parallel, two-group study (IE vs CLE training). SETTING: Multidisciplinary, outpatient, hospital-based, pulmonary rehabilitation program. PATIENTS: Nineteen patients with stable advanced COPD (mean +/- SEM FEV1, 40 +/- 4% predicted). INTERVENTIONS: Patients (n = 10) assigned to IE training exercised at a mean intensity of 124 +/- 15% of baseline peak exercise capacity (peak work rate [Wpeak]) with 30-s work periods interspersed with 30-s rest periods for 45 min/d. Patients (n = 9) allocated to CLE training exercised at a mean intensity of 75 +/- 5% Wpeak for 30 min/d. Patients exercised 3 d/wk for 10 weeks. MEASUREMENTS AND RESULTS: Needle biopsies of the right vastus lateralis muscle were performed before and after rehabilitation. After IE training, the cross-sectional areas of type I and IIa fibers were significantly increased (type I before, 3,972 +/- 455 microm2; after, 4,934 +/- 467 microm2 [p = 0.004]; type IIa before, 3,695 +/- 372 microm2; after, 4,486 +/- 346 microm2 [p = 0.008]), whereas the capillary-to-fiber ratio was significantly enlarged (from 1.13 +/- 0.08 to 1.24 +/- 0.07 [p = 0.013]). Citrate synthase activity increased (from 14.3 +/- 1.4 to 20.5 +/- 4.2 micromol/min/g), albeit not significantly (p = 0.097). There was also a significant improvement in Wpeak (by 19 +/- 5%; p = 0.04) and in lactate threshold (by 17 +/- 5%; p = 0.02). The magnitude of changes in all the above variables was not significantly different compared to that incurred after CLE training. During training sessions, however, ratings of dyspnea and leg discomfort, expressed as fraction of values achieved at baseline Wpeak, were significantly lower (p < 0.05) for IE training (73 +/- 9% and 60 +/- 8%, respectively) compared to CLE training (83 +/- 10% and 87 +/- 13%, respectively). CONCLUSIONS: High-intensity IE training is equally effective to moderately intense CLE training in inducing peripheral muscle adaptations; however, IE is associated with fewer training symptoms.     

Brain metastases from epithelial ovarian cancer. The Hellenic Cooperative Oncology Group (HeCOG) experience and review of the literature

BACKGROUND: Brain metastases from epithelial ovarian cancer (EOC) are rare. A retrospective study of all patients diagnosed with brain metastases from EOC over the last 20 years, according to the Hellenic Cooperative Oncology Group (HeCOG) tumor registry, was conducted. PATIENTS AND METHODS: A total of 1450 patients with EOC were treated within various HeCOG protocols from 1983 to 2004. Seventeen (1.17%) of them developed brain metastases. RESULTS: The median age at diagnosis of brain metastases was 58 years (range, 24 to 77). At initial diagnosis, 2 patients had stage II, 12 had stage III and 3 had stage IV disease. Serous papillary adenocarcinoma was the most common histological subtype [12 patients (71%)]. All patients had received initial cisplatin-based chemotherapy. The median time from initial diagnosis to central nervous system (CNS) relapse was 15.9 months (range, 1.4 to 70.8). The CNS was the only site of disease in 13 (76.5%) patients, whereas 4 (23.5%) patients had additional extracranial disease. Two (12%) patients with isolated single brain lesions underwent surgical excision of the metastases, followed by whole brain radiation therapy (WBRT) and chemotherapy. Four (24%) patients were treated with WBRT alone, 6 (35%) patients with WBRT plus chemotherapy and 2 (12%) had only supportive care, while 3 (18%) patients decided not to have any further treatment after the diagnosis of brain metastases. The median survival time from diagnosis of CNS relapse was 5.7 months (range, 0.2 to 22.6) and the median survival time from diagnosis of EOC was 27.4 months (range, 3.0 to 71.4). In patients with CNS recurrence as the only site of disease, the median survival time from diagnosis of CNS relapse was 5.3 months (range, 0.6 to 22.6) and in those with both CNS and extracranial disease, the median survival time was 3.9 months (range, 0.2 to 11.9) (p=0.5597). There was a statistically significant difference in survival for those treated with WBRT plus chemotherapy (10.0 months) versus those treated with WBRT alone (1.5 months) and those who had only supportive care (0.2 months) (p=0.0003). CONCLUSION: The incidence of cerebral metastases in our patients with EOC was 1.17%, which is consistent with the mean value of all series reported in the literature. The prognosis of patients with brain metastases from EOC is poor. Patients who had WBRT and chemotherapy fared better than those who received WBRT alone.     

Imaging of metastatic orbital leiomyosarcoma

A 74-year-old man with a previous history of lower leg soft tissues leiomyosarcoma and multiple metastasis presented with a progressive painless proptosis of the left eye. Orbital ultrasound, CT, and MRI revealed a large mass in the left medial orbit. The mass was surgically removed and pathologic examination confirmed the diagnosis of a metastatic orbital leiomyosarcoma. The imaging characteristics of this rare tumor are comprehensively detailed, using complementary ultrasound, CT, and MRI, the combination of which allowed planning of total excision of the lesion.     

Diagnosis of a primary uveal extranodal marginal zone B-cell lymphoma by chorioretinal biopsy: case report

Purpose To report the clinical, histopathological and molecular biological findings of a primary extranodal marginal zone B-cell lymphoma (EMZL) of the uvea.Methods Conventional histology, immunohistochemistry and polymerase chain reaction for immunoglobulin heavy chain gene rearrangement (IgH-PCR) and GeneScan analysis were performed on a chorioretinal biopsy.Results Histological examination of the chorioretinal biopsy demonstrated a dense infiltrate of small centrocyte-like cells, plasmacytoid tumour cells and occasional blasts. The tumour cells were positive for CD20, showed monotypical expression for Ig-kappa and IgM, and a growth fraction of 10%. Clonality analysis using IgH-PCR disclosed a monoclonal B-cell population. Following localised irradiation of 35 Gy, a complete remission was achieved.Conclusion This report describes a rare uveal EMZL diagnosed following investigation of a chorioretinal biopsy. Despite its rarity, ophthalmic pathologists should consider the diagnosis of a primary uveal EMZL when reviewing chorioretinal biopsies.     

A rare 33 bp in-frame deletion (alpha63-74 or alpha64-74 or alpha65-75) in the alpha1-globin gene causing alpha(+)-thalassemia: a second observation

The most frequent defects resulting in alpha-thalassemia (thal) include large deletions that remove one or both of the duplicated alpha-globin genes on chromosome 16. Less commonly, alpha-thal mutations involve single nucleotide substitutions or micro-deletions, leading either directly to decreased alpha-globin chain synthesis by the affected allele, or indirectly through production of hyperunstable variant alpha-globin chains. Here we describe the characterization of a 33 bp in-frame deletion within the alpha1-globin gene, in a woman with hematological findings consistent with an alpha-thal trait. The amino acids predicted to be missing as a result of the 33 bp deletion are at the end of the E helix and the EF corner of the alpha-globin protein chain, and are not normally involved in the heme contact, although it is presumed that alpha-globin chain folding and hemoglobin (Hb) formation will be disrupted. The observation of inclusion and Heinz bodies indicates the synthesis of some abnormal Hb (or globin chains). An identical mutation has been previously observed in a single case, a Canadian individual of Greek descent, indicating that it is a rare mutation, and probably of the same origin. Possible mechanisms underlying the mutation at the DNA level are discussed.     

The effect of exercise-induced hypoxemia on blood redox status in well-trained rowers

Exercise-induced arterial hypoxemia (EIAH), characterized by decline in arterial oxyhemoglobin saturation (SaO(2)), is a common phenomenon in endurance athletes. Acute intensive exercise is associated with the generation of reactive species that may result in redox status disturbances and oxidation of cell macromolecules. The purpose of the present study was to investigate whether EIAH augments oxidative stress as determined in blood plasma and erythrocytes in well-trained male rowers after a 2,000-m rowing ergometer race. Initially, athletes were assigned into either the normoxemic (n = 9, SaO(2) >92%, [Formula: see text]: 62.0 ± 1.9 ml kg(-1) min(-1)) or hypoxemic (n = 12, SaO(2) <92%, [Formula: see text]: 60.5 ± 2.2 ml kg(-1 )min(-1), mean ± SEM) group, following an incremental [Formula: see text] test on a wind resistance braked rowing ergometer. On a separate day the rowers performed a 2,000-m all-out effort on the same rowing ergometer. Following an overnight fast, blood samples were drawn from an antecubital vein before and immediately after the termination of the 2,000-m all-out effort and analyzed for selective oxidative stress markers. In both the normoxemic (SaO(2): 94.1 ± 0.9%) and hypoxemic (SaO(2): 88.6 ± 2.4%) rowers similar and significant exercise increase in serum thiobarbituric acid-reactive substances, protein carbonyls, catalase and total antioxidant capacity concentration were observed post-2,000 m all-out effort. Exercise significantly increased the oxidized glutathione concentration and decreased the ratio of reduced (GSH)-to-oxidized (GSSG) glutathione in the normoxemic group only, whereas the reduced form of glutathione remained unaffected in either groups. The increased oxidation of GSH to GSSG in erythrocytes of normoxemic individuals suggest that erythrocyte redox status may be affected by the oxygen saturation degree of hemoglobin. Our findings indicate that exercise-induced hypoxemia did not further affect the increased blood oxidative damage of lipids and proteins observed after a 2,000-m rowing ergometer race in highly-trained male rowers. The present data do not support any potential link between exercise-induced hypoxemia, oxidative stress increase and exercise performance.