Trabeculectomy and optic nerve head topography

The objective of the present study was to evaluate changes in optic nerve head parameters, measured by confocal laser tomography, before and after trabeculectomy in order to identify outcome measures for the management of glaucoma. The optic nerve head of 22 eyes (22 patients) was analyzed by confocal laser tomography with the Heidelberg retinal tomogram (HRT) before and after trabeculectomy. The median time between the first HRT and surgery was 4.6 months (mean: 7.7 ± 8.3) and the median time between surgery and the second HRT was 10.8 months (mean: 12.0 ± 6.8). The patients were divided into two groups, i.e., those with the highest (group A) and lowest (group B) intraocular pressure (IOP) change after surgery. Differences in the 12 standard topographic parameters before and after surgery for each group were evaluated by the Wilcoxon signed rank test and the differences in these parameters between the two groups were compared by the Mann-Whitney rank sum test. Multiple regression analysis was used to evaluate the influence of the change in IOP (deltaIOP and deltaIOP%) and the changes in the other parameters. There were significant differences in the HRT measures before and after surgery in group A only for cup volume. In group B, no parameter was statistically different. The changes in group A were not significantly different than those in group B for any parameter (P > 0.004, Bonferroni correction for multiple comparisons). deltaIOP and deltaIOP% had a statistically significant effect on delta cup disk area, delta cup volume and delta mean cup depth. Changes in cup shape size were influenced significantly only by deltaIOP. Some optic disc parameters measured by HRT presented a significant improvement after filtering surgery, depending on the amount of IOP reduction. Long-term studies are needed to determine the usefulness of these findings as outcome measures in the management of glaucoma.

Risk factors for excess weight loss and hypernatremia in exclusively breast-fed infants

Data were prospectively obtained from exclusively breast-fed healthy term neonates at birth and from healthy mothers with no obstetric complication to determine risk factors for excess weight loss and hypernatremia in exclusively breast-fed infants. Thirty-four neonates with a weight loss > or = 10% were diagnosed between April 2001 and January 2005. Six of 18 infants who were eligible for the study had hypernatremia. Breast conditions associated with breast-feeding difficulties (P < 0.05), primiparity (P < 0.005), less than four stools (P < 0.001), pink diaper (P < 0.001), delay at initiation of first breast giving (P < 0.01), birth by cesarean section (P < 0.05), extra heater usage (P < 0.005), extra heater usage among mothers who had appropriate conditions associated with breast-feeding (P < 0.001), mean weight loss in neonates with pink diaper (P < 0.05), mean uric acid concentration in neonates with pink diaper (P < 0.0001), fever in hypernatremic neonates (P < 0.02), and the correlation of weight loss with both serum sodium and uric acid concentrations (P < 0.02) were determined. Excessive weight loss occurs in exclusively breast-fed infants and can be complicated by hypernatremia and other morbidities. Prompt initiation of breast-feeding after delivery and prompt intervention if problems occur with breast-feeding, in particular poor breast attachment, breast engorgement, delayed breast milk "coming in", and nipple problems will help promote successful breast-feeding. Careful follow-up of breast-feeding dyads after discharge from hospital, especially regarding infant weight, is important to help detect inadequate breast-feeding. Environmental factors such as heaters may exacerbate infant dehydration.

Analytic evaluation of three-phase short circuit demagnetization and hysteresis loss risk in rotor-surface-magnet Permanent-Magnet Synchronous Machines

Permanent magnet synchronous machines (PMSM) have become widely used in applications because of high efficiency compared to synchronous machines with exciting winding or to induction motors. This feature of PMSM is achieved through the using the permanent magnets (PM) as the main excitation source. The magnetic properties of the PM have significant influence on all the PMSM characteristics. Recent observations of the PM material properties when used in rotating machines revealed that in all PMSMs the magnets do not necessarily operate in the second quadrant of the demagnetization curve which makes the magnets prone to hysteresis losses. Moreover, still no good analytical approach has not been derived for the magnetic flux density distribution along the PM during the different short circuits faults. The main task of this thesis is to derive simple analytical tool which can predict magnetic flux density distribution along the rotor-surface mounted PM in two cases: during normal operating mode and in the worst moment of time from the PM’s point of view of the three phase symmetrical short circuit. The surface mounted PMSMs were selected because of their prevalence and relatively simple construction. The proposed model is based on the combination of two theories: the theory of the magnetic circuit and space vector theory. The comparison of the results in case of the normal operating mode obtained from finite element software with the results calculated with the proposed model shows good accuracy of model in the parts of the PM which are most of all prone to hysteresis losses. The comparison of the results for three phase symmetrical short circuit revealed significant inaccuracy of the proposed model compared with results from finite element software. The analysis of the inaccuracy reasons was provided. The impact on the model of the Carter factor theory and assumption that air have permeability of the PM were analyzed. The propositions for the further model development are presented.

Long-term loss of color vision after exposure to mercury vapor

We evaluated the color vision of 24 subjects (41.6 ± 6.5 years; 6 females) who worked in fluorescent lamp industries. They had been occupationally exposed to mercury vapor (10.6 ± 5.2 years) and had been away from the source of exposure for 6.4 ± 4.04 years. Mean urinary concentration of mercury was 40.6 ± 36.4 µg/g creatinine during or up to 1 year after exposure and 2.71 ± 1.19 µg/g creatinine at the time of color vision testing or up to 1 year thereafter. All patients were diagnosed with chronic mercury intoxication, characterized by clinical symptoms and neuropsychological alterations. A control group (N = 36, 48.6 ± 11.9 years, 10 females, 1.5 ± 0.47 µg mercury/g creatinine) was subjected to the same tests. Inclusion criteria for both groups were Snellen VA 20/30 or better and absence of known ophthalmologic pathologies. Color discrimination was assessed with the Farnsworth D-15 test (D-15) and with the Lanthony D-15d test (D-15d). Significant differences were found between the two eyes of the patients (P < 0.001) in both tests. Results for the worst eye were also different from controls for both tests: P = 0.014 for D-15 and P < 0.001 for D-15d. As shown in previous studies, the D-15d proved to be more sensitive than the D-15 for the screening and diagnosis of the color discrimination losses. Since color discrimination losses were still present many years after the end of exposure, they may be considered to be irreversible, at least under the conditions of the present study.

Impact of marked weight loss induced by bariatric surgery on bone mineral density and remodeling

Data about the impact of bariatric surgery (BS) and subsequent weight loss on bone are limited. The objective of the present study was to determine bone mineral density (BMD), bone remodeling metabolites and hormones that influence bone trophism in premenopausal women submitted to BS 9.8 months, on average, before the study (OGg, N = 16). The data were compared to those obtained for women of normal weight (CG, N = 11) and for obese women (OG, N = 12). Eight patients in each group were monitored for one year, with the determination of BMD, of serum calcium, phosphorus, magnesium, parathyroid hormone, 25-hydroxyvitamin D, insulin-like growth factor-I (IGF-I) and osteocalcin, and of urinary calcium and deoxypyridinoline. The biochemical determinations were repeated every three months in the longitudinal study and BMD was measured at the end of the study. Parathyroid hormone levels were similar in the three groups. IGF-I levels (CG = 332 ± 62 vs OG = 230 ± 37 vs OGg = 128 ± 19 ng/mL) were significantly lower in the operated patients compared to the non-operated obese women. Only OGg patients presented a significant fall in BMD of 6.2% at L1-L4, of 10.2% in the femoral neck, and of 5.1% in the forearm. These results suggest that the weight loss induced by BS is associated with a significant loss of bone mass even at sites that are not influenced by weight overload, with hormonal factors such as IGF-I being associated with this process.

Genetic variations of EBV-LMP1 from nasopharyngeal carcinoma biopsies: potential loss of T cell epitopes

To find Epstein-Barr virus (EBV) strains with genetic variations of EBV latent membrane protein 1 (EBV-LMP1) from nasopharyngeal carcinoma (NPC), the full-length DNA of LMP1 genes from 21 NPC biopsies obtained in Hunan province in southern China was amplified and sequenced. Our sequences were compared to those previously reported by the Clustal V method. Results showed that all 21 sequences displayed two amino acid changes most frequently in LMP1 of CD4+ T cell epitopes at codons 144 (F®I, 21/21) and 212 (G®S, 19/21) or (G®N, 2/21). We also show that type A EBV strain is prevalent in the cases of NPC from Hunan province with a 30-bp 18/21 deletion, and we highlight that this deletion resulted in loss of one of the CD4+ T cell-restricted epitopes. The other 3 sequences without this deletion all had a change at codon 344 (G®D). Furthermore, in the major epitope sequence of CD8+ T cells restricted by HLA-A2, all 21 sequences showed changes at codons 126 (L®F) and 129 (M®I). Our study discovered that one of the 21 sequence variations harbored a new change at codon 131 (W®C), and 5/21 specimens showed another novel change at codon 115 (G®A) in the major epitope sequence of CD8+ T cells restricted by HLA-A2. Our study suggests that these sequence variations of NPC-derived LMP1 may lead to a potential escape from host cell immune recognition, protecting latent EBV infection and causing an increase in tumorigenicity.

Association of loss of heterozygosity with cytogenetic abnormalities in acute myeloid leukemia and myelodysplastic syndrome

Deletions on chromosomes 5 and 7 are frequently seen in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). It is assumed that these deletions indicate loss of tumor suppressor genes on these chromosomes and until these tumor suppressor genes are identified, the functional consequences of these deletions and the molecular basis of these myeloid disorders cannot be completely understood. We evaluated loss of heterozygosity (LOH) in 44 patients (18 MDS and 26 AML, diagnosed according to WHO classification criteria) at diagnosis, using a four-microsatellite marker panel: an intragenic marker on the 7th intron of gene IRF-1 of the 5q31.1 region and three markers located inside the 7q31.1 region and correlated the LOH with karyotype abnormalities. The microsatellites chosen corresponded to chromosome regions frequently deleted in MDS/AML. The samples with Q (peak area) less than or equal to 0.50 were indicative of LOH. The percent of informative samples (i.e., heterozygous) for the intragenic microsatellite in gene IRF-1 and in loci D7S486, D7S515 and D7S522 were 66.6, 73.7, 75.5, and 48.8%, respectively. Cytogenetic abnormalities by G-banding were found in 36% (16/44) of the patients (2 of 18 MDS and 14 of 26 AML patients). We found a significantly positive association of the occurrence of LOH with abnormal karyotype (P < 0.05; chi-square test) and there were cases with LOH but the karyotype was normal (by G-banding). These data indicate that LOH in different microsatellite markers is possibly an event previous to chromosomal abnormalities in these myeloid neoplasias.

Systematic head and neck physical examination as a predictor of obstructive sleep apnea in class III obese patients

Our aim was to determine if anatomical abnormalities of the upper airway (UA) and facial skeleton of class III severely obese patients are related to the presence and severity of obstructive sleep apnea syndrome (OSAS). Forty-five patients (69% females, mean age 46.5 ± 10.8 years) with a body mass index (BMI) over 40 kg/m² underwent UA and facial skeletal examinations as well as polysomnography. Mean BMI was 49 ± 7 kg/m² and mean neck circumference was 43.4 ± 5.1 cm. Polysomnographic findings showed that 22% had a normal apnea-hypopnea index (AHI) and 78% had an AHI over 5. The presence of OSAS was associated with younger age (P = 0.02), larger neck circumference (P = 0.004), presence of a voluminous lateral wall (P = 0.0002), posteriorized soft palate (P = 0.0053), thick soft palate (P = 0.0014), long uvula (P = 0.04), thick uvula (P = 0.0052), and inferior turbinate hypertrophy (P = 0.04). A larger neck circumference (P = 0.02), presence of a voluminous lateral wall (P = 0.04), posteriorized soft palate (P = 0.03), and thick soft palate (P = 0.04) were all associated with OSAS severity. The prevalence of OSAS in this group was high. A larger neck circumference and soft tissue abnormalities of the UA were markers for both the presence and severity of OSAS. Conversely, no abnormalities in the facial skeleton were associated with OSAS in patients with morbid obesity.

Classification and hearing evolution of patients with sudden sensorineural hearing loss

The aim of this study was to analyze clinical aspects, hearing evolution and efficacy of clinical treatment of patients with sudden sensorineural hearing loss (SSNHL). This was a prospective clinical study of 136 consecutive patients with SSNHL divided into three groups after diagnostic evaluation: patients with defined etiology (DE, N = 13, 10%), concurrent diseases (CD, N = 63, 46.04%) and idiopathic sudden sensorineural hearing loss (ISSHL, N = 60, 43.9%). Initial treatment consisted of prednisone and pentoxifylline. Clinical aspects and hearing evolution for up to 6 months were evaluated. Group CD comprised 73% of patients with metabolic decompensation in the initial evaluation and was significantly older (53.80 years) than groups DE (41.93 years) and ISSHL (39.13 years). Comparison of the mean initial and final hearing loss of the three groups revealed a significant hearing improvement for group CD (P = 0.001) and group ISSHL (P = 0.001). Group DE did not present a significant difference in thresholds. The clinical classification for SSNHL allows the identification of significant differences regarding age, initial and final hearing impairment and likelihood of response to therapy. Elevated age and presence of coexisting disease were associated with a greater initial hearing impact and poorer hearing recovery after 6 months. Patients with defined etiology presented a much more limited response to therapy. The occurrence of decompensated metabolic and cardiovascular diseases and the possibility of first manifestation of auto-immune disease and cerebello-pontine angle tumors justify an adequate protocol for investigation of SSNHL.

Genetic variability of vascular endothelial growth factor and prognosis of head and neck cancer in a Brazilian population

Vascular endothelial growth factor (VEGF) is one of the most potent endothelial cell mitogens and plays a critical role in angiogenesis. Polymorphisms in this gene have been evaluated in patients with several types of cancer. The objectives of this study were to determine if there was an association of the -1154G/A polymorphism of the VEGF gene with head and neck cancer and the interaction of this polymorphism with lifestyle and demographic factors. Additionally, the distribution of the VEGF genotype was investigated with respect to the clinicopathological features of head and neck cancer patients. The study included 100 patients with histopathological diagnosis of head and neck squamous cell carcinoma. Patients with treated tumors were excluded. A total of 176 individuals 40 years or older were included in the control group and individuals with a family history of neoplasias were excluded. Analysis was performed after extraction of genomic DNA using the real-time PCR technique. No statistically significant differences between allelic and genotype frequencies of -1154G/A VEGF polymorphism were identified between healthy individuals and patients. The real-time PCR analyses showed a G allele frequency of 0.72 and 0.74 for patients and the control group, respectively. The A allele showed a frequency of 0.28 for head and neck cancer patients and 0.26 for the control group. However, analysis of the clinicopathological features showed a decreased frequency of the A allele polymorphism in patients with advanced (T3 and T4) tumors (OR = 0.36; 95%CI = 0.14-0.93; P = 0.0345). The -1154A allele of the VEGF gene may decrease the risk of tumor growth and be a possible biomarker for head and neck cancer. This polymorphism is associated with increased VEGF production and may have a prognostic importance.

5-Methyltetrahydrofolate-homocysteine methyltransferase gene polymorphism (MTR) and risk of head and neck cancer

The functional effect of the A>G transition at position 2756 on the MTR gene (5-methyltetrahydrofolate-homocysteine methyltransferase), involved in folate metabolism, may be a risk factor for head and neck squamous cell carcinoma (HNSCC). The frequency of MTR A2756G (rs1805087) polymorphism was compared between HNSCC patients and individuals without history of neoplasias. The association of this polymorphism with clinical histopathological parameters was evaluated. A total of 705 individuals were included in the study. The polymerase chain reaction-restriction fragment length polymorphism technique was used to genotype the polymorphism. For statistical analysis, the chi-square test (univariate analysis) was used for comparisons between groups and multiple logistic regression (multivariate analysis) was used for interactions between the polymorphism and risk factors and clinical histopathological parameters. Using univariate analysis, the results did not show significant differences in allelic or genotypic distributions. Multivariable analysis showed that tobacco and alcohol consumption (P < 0.05), AG genotype (P = 0.019) and G allele (P = 0.028) may be predictors of the disease and a higher frequency of the G polymorphic allele was detected in men with HNSCC compared to male controls (P = 0.008). The analysis of polymorphism regarding clinical histopathological parameters did not show any association with the primary site, aggressiveness, lymph node involvement or extension of the tumor. In conclusion, our data provide evidence that supports an association between the polymorphism and the risk of HNSCC.

Glomerular damage as a predictor of renal allograft loss

Interstitial fibrosis and tubular atrophy (IF/TA) are the most common cause of renal graft failure. Chronic transplant glomerulopathy (CTG) is present in approximately 1.5-3.0% of all renal grafts. We retrospectively studied the contribution of CTG and recurrent post-transplant glomerulopathies (RGN) to graft loss. We analyzed 123 patients with chronic renal allograft dysfunction and divided them into three groups: CTG (N = 37), RGN (N = 21), and IF/TA (N = 65). Demographic data were analyzed and the variables related to graft function identified by statistical methods. CTG had a significantly lower allograft survival than IF/TA. In a multivariate analysis, protective factors for allograft outcomes were: use of angiotensin-converting enzyme inhibitor (ACEI; hazard ratio (HR) = 0.12, P = 0.001), mycophenolate mofetil (MMF; HR = 0.17, P = 0.026), hepatitis C virus (HR = 7.29, P = 0.003), delayed graft function (HR = 5.32, P = 0.016), serum creatinine ≥1.5 mg/dL at the 1st year post-transplant (HR = 0.20, P = 0.011), and proteinuria ≥0.5 g/24 h at the 1st year post-transplant (HR = 0.14, P = 0.004). The presence of glomerular damage is a risk factor for allograft loss (HR = 4.55, P = 0.015). The presence of some degree of chronic glomerular damage in addition to the diagnosis of IF/TA was the most important risk factor associated with allograft loss since it could indicate chronic active antibody-mediated rejection. ACEI and MMF were associated with better outcomes, indicating that they might improve graft survival.

A link between sleep loss, glucose metabolism and adipokines

The present review evaluates the role of sleep and its alteration in triggering problems of glucose metabolism and the possible involvement of adipokines in this process. A reduction in the amount of time spent sleeping has become an endemic condition in modern society, and a search of the current literature has found important associations between sleep loss and alterations of nutritional and metabolic contexts. Studies suggest that sleep loss is associated with problems in glucose metabolism and a higher risk for the development of insulin resistance and type 2 diabetes mellitus. The mechanism involved may be associated with the decreased efficacy of regulation of the hypothalamus-pituitary-adrenal axis by negative feedback mechanisms in sleep-deprivation conditions. In addition, changes in the circadian pattern of growth hormone (GH) secretion might also contribute to the alterations in glucose regulation observed during sleep loss. On the other hand, sleep deprivation stress affects adipokines - increasing tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and decreasing leptin and adiponectin -, thus establishing a possible association between sleep-debt, adipokines and glucose metabolism. Thus, a modified release of adipokines resulting from sleep deprivation could lead to a chronic sub-inflammatory state that could play a central role in the development of insulin resistance and type 2 diabetes mellitus. Further studies are necessary to investigate the role of sleep loss in adipokine release and its relationship with glucose metabolism.

Education, tobacco smoking, alcohol consumption, and IL-2 and IL-6 gene polymorphisms in the survival of head and neck cancer

The association of education, tobacco smoking, alcohol consumption, and interleukin-2 (IL-2 +114 and -384) and -6 (IL-6 -174) DNA polymorphisms with head and neck squamous cell carcinoma (HNSCC) was investigated in a cohort study of 445 subjects. IL-2 and IL-6 genotypes were determined by real-time PCR. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) of disease-specific survival according to anatomical sites of the head and neck. Mean age was 56 years and most patients were males (87.6%). Subjects with 5 or more years of schooling had better survival in larynx cancer. Smoking had no effect on HNSCC survival, but alcohol consumption had a statistically significant effect on larynx cancer. IL-2 gene +114 G/T (HR = 0.52; 95%CI = 0.15-1.81) and T/T (HR = 0.22; 95%CI = 0.02-3.19) genotypes were associated with better survival in hypopharynx cancer. IL-2 +114 G/T was a predictor of poor survival in oral cavity/oropharynx cancer and larynx cancer (HR = 1.32; 95%CI = 0.61-2.85). IL-2 -384 G/T was associated with better survival in oral cavity/oropharynx cancer (HR = 0.80; 95%CI = 0.45-1.42) and hypopharynx cancer (HR = 0.68; 95%CI = 0.21-2.20), but an inverse relationship was observed for larynx cancer. IL-6 -174 G/C was associated with better survival in hypopharynx cancer (HR = 0.68; 95%CI = 0.26-1.78) and larynx cancer (HR = 0.93; 95%CI = 0.42-2.07), and C/C reduced mortality in larynx cancer. In general, our results are similar to previous reports on the value of education, smoking, alcohol consumption, and IL-2 and IL-6 genetic polymorphisms for the prognosis of HNSCC, but the risks due to these variables are small and estimates imprecise.

Hypoxic-ischemic injury decreases anxiety-like behavior in rats when associated with loss of tyrosine-hydroxylase immunoreactive neurons of the substantia nigra

Neonatal Sprague-Dawley rats were randomly divided into normal control, mild hypoxia-ischemia (HI), and severe HI groups (N = 10 in each group at each time) on postnatal day 7 (P7) to study the effect of mild and severe HI on anxiety-like behavior and the expression of tyrosine hydroxylase (TH) in the substantia nigra (SN). The mild and severe HI groups were exposed to hypoxia (8% O2/92% N2) for 90 and 150 min, respectively. The elevated plus-maze (EPM) test was performed to assess anxiety-like behavior by measuring time spent in the open arms (OAT) and OAT%, and immunohistochemistry was used to determine the expression of TH in the SN at P14, P21, and P28. OAT and OAT% in the EPM were significantly increased in both the mild (1.88-, 1.99-, and 2.04-fold, and 1.94-, 1.51-, and 1.46-fold) and severe HI groups (1.69-, 1.68-, and 1.87-fold, and 1.83-, 1.43-, and 1.39-fold, respectively; P < 0.05). The percent of TH-positive cells occupying the SN area was significantly and similarly decreased in both the mild (17.7, 40.2, and 47.2%) and severe HI groups (16.3, 32.2, and 43.8%, respectively; P < 0.05). The decrease in the number of TH-positive cells in the SN and the level of protein expression were closely associated (Pearson correlation analysis: r = 0.991, P = 0.000 in the mild HI group and r = 0.974, P = 0.000 in the severe HI group) with the impaired anxiety-like behaviors. We conclude that neonatal HI results in decreased anxiety-like behavior during the juvenile period of Sprague-Dawley rats, which is associated with the decreased activity of TH in the SN. The impairment of anxiety and the expression of TH are not likely to be dependent on the severity of HI.