Thalamic hypometabolism in a patient undergoing vagal nerve stimulation seen on F-18 FDG PET imaging

A 31-year-old man with a vagal nerve stimulator for seizure control was noted to have decreased metabolism within the thalamus as visualized by F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET). Some investigators think the thalamus plays an important role in the regulation of seizure activity. Vagal nerve stimulation (VNS) may reduce thalamic activity, which in turn may reduce seizure activity. However, because the thalamus has diffuse connections throughout the brain, its role in seizure activity is likely complex. Observing decreased thalamic activity during VNS is just 1 small step toward understanding this role.     

Hearing impairment and socioeconomic factors: a population-based survey of an urban locality in southern Brazil.

OBJECTIVE: To provide the first population-based data on deafness and hearing impairment in Brazil. METHODS: In 2003, a cross-sectional household survey was conducted of 2,427 persons 4 years old and over. The study population was composed of 1,040 systematically chosen households in 40 randomly selected census tracts (dwelling clusters) in the city of Canoas, which is in the state of Rio Grande do Sul, in southern Brazil. Hearing function was evaluated in all subjects by both pure-tone audiometry and physical examination, using the World Health Organization Ear and Hearing Disorders Survey Protocol and definitions of hearing levels. The socioeconomic data that were gathered included the amount of schooling of all individuals tested and the income of the head of the household. RESULTS: It was found that 26.1% of the population studied showed some level of hearing impairment, and 6.8% (95% confidence interval (CI) = 5.5%-8.1%) were classified in the disabling hearing impairment group. The prevalence of moderate hearing loss was 5.4% (95% CI = 4.4%-6.4%); for severe hearing loss, 1.2% (95% CI = 0.7%-1.7%); and for profound hearing loss, 0.2% (95% CI = 0.03%-0.33%). The groups at higher risk for hearing loss were men (odds ratio (OR) = 1.54; 95% CI = 1.06-2.23); participants 60 years of age and over (OR = 12.55; 95% CI = 8.38-18.79); those with fewer years of formal schooling (OR = 3.92; 95% CI = 2.14-7.16); and those with lower income (OR = 1.56; 95% CI = 1.06-2.27). CONCLUSIONS: These results support advocacy by health policy planners and care providers for the prevention of deafness and hearing impairment. The findings could help build awareness in the community, in universities, and in government agencies of the health care needs that hearing problems create.     

Activity of cisplatin and ICI 182,780 on estrogen receptor negative ovarian cancer cells: cell cycle and cell replication rate perturbation, chromatin texture alteration and apoptosis induction

The activity of cisplatin (CP, range of concentrations 0.25-1 microg/ml), the pure steroidal antiestrogen compound ICI 182,780 (range of concentrations, 0.01-10 microM) and various combinations of, was investigated on an estrogen receptor negative ovarian cancer cell line (A2780 WT) and its CP-resistant derivative subline (A2780 CP3). CP markedly reduced A2780 WT cell growth but marginally affected A2780 CP3, whereas ICI 182,780 was effective on both cell lines. CP but not ICI 182,780 provoked a significant blockade in late S/G(2) phase in both cell lines, particularly in the parental line. Measuring the number of rounds of cell replications showed that CP diminished the cell replication rate of both cell lines, particularly in A2780 WT. Conversely, ICI 182,780 reduced the cell replication rate of A2780 CP3 but not A2780 WT cells. Both drugs provoked apoptosis in A2780 WT cells, as assessed by the appearance of large (50-300 kbp) DNA fragmentation. However, laser scanning cytometry showed that only CP induced a measurable alteration of chromatin texture in A2780 WT but not in A2780 CP3 cells. The combination CP and ICI 182,780 resulted in a synergistic inhibitory activity of cell growth with a CP potentiation up to 4 and 11-fold in A2780 WT and A2780 CP3 cells, respectively. This reflected an enhanced reduction of the cell replication rate and did not involve perturbations of the cell cycle other than those provoked by CP alone. Apoptosis induction and the level of CP-DNA adducts were not influenced by adding ICI 182,780 to CP in both cell lines.     

Mechanisms of pain in distal symmetric polyneuropathy: A combined clinical and neurophysiological study

In patients with distal symmetric polyneuropathy we assessed non-nociceptive Aβ- and nociceptive Aδ-afferents to investigate their role in the development of neuropathic pain. We screened 2240 consecutive patients with sensory disturbances and collected 150 patients with distal symmetric polyneuropathy (68 with pain and 82 without). All patients underwent the Neuropathic Pain Symptom Inventory to rate ongoing, paroxysmal and provoked pains, a standard nerve conduction study (NCS) to assess Aβ-fibre function, and laser-evoked potentials (LEPs) to assess Aδ-fibre function. Patients with pain had the same age (P > 0.50), but a longer delay since symptom onset than those without (P < 0.01). Whereas the LEP amplitude was significantly lower in patients with pain than in those without (P < 0.0001), NCS data did not differ between groups (P > 0.50). LEPs were more severely affected in patients with ongoing pain than in those with provoked pain (P < 0.0001). Our findings indicate that the impairment of Aβ-fibres has no role in the development of ongoing or provoked pain. In patients with ongoing pain the severe LEP suppression and the correlation between pain intensity and LEP attenuation may indicate that this type of pain reflects damage to nociceptive axons. The partially preserved LEPs in patients with provoked pain suggest that this type of pain is related to the abnormal activity arising from partially spared and sensitised nociceptive terminals. Because clinical and neurophysiological abnormalities followed similar patterns regardless of aetiology, pain should be classified and treated on mechanism-based grounds.     

Relation of various plasma growth factor levels in patients with stable angina pectoris and total occlusion of a coronary artery to the degree of coronary collaterals

We assessed (1) angiogenic factors in patients with stable angina and longstanding (> or =24 months) total occlusion of a single coronary artery and (2) the relation between plasma levels of angiogenic factors and the development of collateral vessels as evaluated by coronary angiography. Plasma concentrations of vascular endothelial growth factor (VEGF(165)), fibroblast growth factor, placenta-derived growth factors (PlGFs), and hepatocyte growth factor were assessed in 96 patients with stable angina and longstanding (> or =24 months) total occlusion of a single coronary artery. According to coronary angiographic results, 18 patients had no visible collaterals (group 0), 21 patients had visible collaterals but no filling of the recipient epicardial vessel (group 1), and 57 patients showed filling (partial or complete) of the recipient epicardial vessel by collaterals (group 2). Plasma VEGF(165) and PlGF concentrations were higher in group 1 than in groups 0 and 2 (VEGF(165) 75 pg/ml, range 24 to 105, vs 23 pg/ml, range 15 to 29, and 19 pg/ml, range 10 to 41, respectively, F = 5.53, p = 0.006; PlGF 35 pg/ml, range 3.5 to 105, vs 1 pg/ml, range 1 to 38, and 1 pg/ml, range 1 to 5, respectively, F = 7.09, p = 0.008). Plasma VEGF(165) and PlGF levels were similar in groups 0 and 2. There was no significant difference in plasma levels of fibroblast and hepatocyte growth factor concentrations across the 3 groups. In conclusion, plasma levels of angiogenic growth factors differ among patients with stable angina pectoris and longstanding total coronary occlusion.     

Effects of IL-6 variants in multiple myeloma: growth inhibition and induction of apoptosis in primary cells

Interleukin-6 (IL-6) plays a pathogenetic role in B-cell malignancies and is a growth factor for multiple myeloma (MM) cells. Elevated serum IL-6 levels and a higher proliferative activity of bone marrow plasma cells are poor prognostic factors in MM patients. In addition to clinical trials with anti-IL-6 monoclonal antibodies, an alternative therapeutic approach based on the use of IL-6 receptor (R) super-antagonists (Sants) has been proposed. Sants are variants of the native cytokine characterized by a wild type affinity for the ligand-specific receptor chain IL-6R alpha and by a reduced ability to bind and/or dimerize the signaling chain gp-130. We report the in vitro effects of four different Sants on cell kinetic modulation and induction of apoptosis of primary cells from MM patients. Ten MM samples were cultured in the presence of four different Sants and heterogeneous effects in terms of reduction of proliferation and induction of apoptosis could be observed. A decrease of the S phase cells (> or = 25%) coupled with the induction of apoptosis was obtained in 4/10 samples: three of these samples had a diploid DNA stem line and an inferior initial percentage of S phase cells. Serum IL-6 concentrations did not correlate with the anti-proliferative activities of the Sants. Cell growth inhibition was observed especially in samples with soluble IL-6R serum concentrations > 200 ng/ml. We conclude that Sants can exert antiproliferative effects on selected MM samples. Such effects may depend on the availability of large amounts of soluble IL-6R. Further studies should aim at defining the conditions necessary for optimal antiproliferative activity.     

A small molecule Smac mimic potentiates TRAIL-mediated cell death of ovarian cancer cells

OBJECTIVES: Ovarian cancer remains a leading cause of death in women and development of new therapies is essential. Second mitochondria derived activator of caspase (Smac) has been described to sensitize for apoptosis. We have explored the proapoptotic activity of a small molecule mimic of Smac/DIABLO on ovarian cancer cell lines (A2780 cells and its chemoresistant derivatives A2780/ADR and A2780/DDP), cancer cell lines and in primary ovarian cancer cells. METHODS: The effects of a small molecule mimic of Smac/DIABLO on ovarian cancer cell lines and primary ovarian cancer cells were determined by cell proliferation, apoptosis and biochemical assays. RESULTS: This compound added alone elicited only a weak proapoptotic effect; however, it strongly synergizes with tumor necrosis factor-related apoptosis inducing ligand (TRAIL) or agonistic TRAILR2 antibody (Lexatumumab) in inducing apoptosis of ovarian cancer cells. CONCLUSIONS: These observations suggest that small molecule mimic of Smac/DIABLO could be useful for the development of experimental strategies aiming to treat ovarian cancer. Interestingly, in addition to its well known proapoptotic effects, Smac/DIABLO elicited a significant increase of pro-caspase-3 levels.     

Temporal variation in the prevalence of weight and obesity excess in adults: Brazil, 2006 to 2009

Overweight and obesity are public health issues that affect an important part of the world population. This study aims at describing the trends in overweight and obesity prevalence rates from 2006 to 2009, by means of telephone surveys in 27 Brazilian cities, with a population aged 18 years or older. The body mass index (BMI) was calculated by the reported height and weight; overweight and obesity were considered as BMI >25 kg/m2 and >30 kg/m2, respectively. Temporal variation in overweight and obesity prevalence is presented for men and women, according to age group, schooling, stable relationship, and skin color. Poisson regression was used for the analysis. Overweight prevalence was 43.0, 42.7, 44.2 and 46.6%,for each year of the period from 2006 to 2009, respectively. For obesity, in the same period, the trend was: 11.4, 12.7, 13.2 and 13.8%. The temporal trend varied in relation to some demographic and socioeconomic variables. The prevalence was higher among women and young adults. The temporal trend was independent of the relationship status of the interviewees, but the prevalence was higher among white women and those with less years of schooling. The results in this study confirmed the urgent need for effective prevention and control measures, as the increasing trend is occurring in a short period of time, especially among youngsters.     

Aging, immunity, and critical care nursing

Age-related changes of the immune system along with underlying disease can reduce the elderly patients' chances of survival in critical care. Complications can be minimized when the health care team responds not only to the needs of the critically ill patient, but also to the needs specific to the elderly patient.