The Effects of Continuous Positive Airway Pressure on Prehypertension and Masked Hypertension in Men With Severe Obstructive Sleep Apnea

Obstructive sleep apnea and hypertension are common conditions that frequently coexist. Continuous positive airway pressure (CPAP) reduces blood pressure in patients with obstructive sleep apnea and sustained hypertension. However, the impact of CPAP on patients with obstructive sleep apnea and prehypertension and masked hypertension, conditions associated with increased cardiovascular risk, is unknown. Thirty-six male patients (age, 43 +/- 7 years; body mass index, 28.8 +/- 3.0 kg/m(2)) with untreated severe obstructive sleep apnea (apnea-hypopnea index, 56 +/- 22 events/hr on polysomnography) with diagnostic criteria for prehypertension and/or masked hypertension, based on office and 24-hour ambulatory blood pressure monitoring, respectively, were studied. The patients randomized to no treatment (control; n=18) or CPAP (n=18) for 3 months had similar frequency of prehypertension and masked hypertension at study entry. There were no significant changes in blood pressure in patients randomized to the control group. In contrast, patients randomized to CPAP presented significant reduction in office systolic (from 126 +/- 5 to 121 +/- 7 mm Hg; P=0.001) and a trend for diastolic blood pressure (from 75 +/- 7 to 73 +/- 8 mm Hg; P=0.08) as well as a significant decrease in daytime and nighttime systolic and diastolic blood pressure (P < 0.05 for each comparison). There was a significant reduction in the frequency of prehypertension (from 94% to 55%; P=0.02) and masked hypertension (from 39% to 5%; P=0.04) only in the CPAP group. In conclusion, effective CPAP therapy promotes significant reduction in the frequency of prehypertension and masked hypertension by promoting significant blood pressure reductions in patients with severe obstructive sleep apnea. (Hypertension. 2011;57[part 2]:549-555.)

Cardiopulmonary Effects of Matching Positive End-Expiratory Pressure to Abdominal Pressure in Concomitant Abdominal Hypertension and Acute Lung Injury

Background: To evaluate the cardiopulmonary effects of positive end-expiratory pressure (PEEP) equalization to intra-abdominal pressure (IAP) in an experimental model of intra-abdominal hypertension (IAH) and acute lung injury (ALI). Methods: Eight anesthetized pigs were submitted to IAH of 20 mm Hg with a carbon dioxide insufflator for 30 minutes and then submitted to lung lavage with saline and Tween (2.5%). Pressure x volume curves of the respiratory system were performed by a low flow method during IAH and ALI, and PEEP was subsequently adjusted to 27 cm center dot H(2)O for 30 minutes. Results: IAH decreases pulmonary and respiratory system static compliances and increases airway resistance, alveolar-arterial oxygen gradient, and respiratory dead space. The presence of concomitant ALI exacerbates these findings. PEEP identical to AP moderately improved oxygenation and respiratory mechanics; however, an important decline in stroke index and right ventricle ejection fraction was observed. Conclusions: Simultaneous IAH and ALI produce important impairments in the respiratory physiology. PEEP equalization to AP may improve the respiratory performance, nevertheless with a secondary hemodynamic derangement.

Estrogen receptor-positive breast carcinomas in younger women are different from those of older women: A pathological and immunohistochemical study

The higher frequency of triple-negative and HER-2-positive tumors detected in younger patients has been suggested as an explanation for the more aggressive tumor types observed in this age group. However, estrogen receptor (ER)-positive tumors are the most frequent subtype of breast carcinomas identified, even in younger patients. In this retrospective study, the morphological and immunohistochemical profiles of ER-positive breast carcinomas from women 35 yrs and younger that were diagnosed between 1997 and 2007 were evaluated. From these cases, 213 were selected based on the availability of pathology reports and paraffin blocks. For comparison, 117 consecutive cases of breast carcinomas diagnosed in patients >60 yrs from 2006 were included. Paraffin-embedded tumors were stained for expression of ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2). Ki-67 antigen, epidermal growth factor receptor (EGFR), cytokeratin 5/6, p53, vimentin, CD117, and p63 using tissue microarrays. ER-positive carcinomas were diagnosed in 120 (56.1%) samples of the younger patient group and in 92 (78.6%) samples of the older patient group. Of these ER-positive carcinomas, 48 (40%) from the younger patient group presented the subtype luminal A, compared with 53 (57.6%) from the older patient group (p=0.01). Tumors from the younger patient group were also associated with increased vascular involvement, co-expression of HER-2, and decreased expression of CD117. These results highlight differences in expression markers and the pathology of ER-positive tumors detected in younger women, with a notable characteristic being co-expression of HER-2. (C) 2010 Elsevier Ltd. All rights reserved.

Increased number and function of natural killer cells in human immunodeficiency virus 1-positive subjects co-infected with herpes simplex virus 2

P>Natural killer (NK) cells bridge the interface between innate and adaptive immunity and are implicated in the control of herpes simplex virus 2 (HSV-2) infection. In subjects infected with human immunodeficiency virus 1 (HIV-1), the critical impact of the innate immune response on disease progression has recently come into focus. Higher numbers of NK cells are associated with lower HIV-1 plasma viraemia. Individuals with the compound genotype of killer cell immunoglobulin-like receptor (KIR) 3DS1 and human leucocyte antigen (HLA)-Bw4-80I, or who have alleles of KIR3DL1 that encode proteins highly expressed on the NK cell surface, have a significant delay in disease progression. We studied the effect of HSV-2 co-infection in HIV-1-infected subjects, and show that HSV-2 co-infection results in a pan-lymphocytosis, with elevated absolute numbers of CD4+ and CD8+ T cells, and NK cells. The NK cells in HSV-2 co-infected subjects functioned more efficiently, with an increase in degranulation after in vitro stimulation. The number of NK cells expressing the activating receptors NKp30 and NKp46, and expressing KIR3DL1 or KIR3DS1, was inversely correlated with HIV-1 plasma viral load in subjects mono-infected with HIV-1, but not in subjects co-infected with HSV-2. This suggests that HSV-2 infection mediates changes within the NK cell population that may affect immunity in HIV-1 infection.

Combination of Multiple Molecular Markers Can Improve Prognostication in Patients With Locally Advanced and Lymph Node Positive Bladder Cancer

Purpose: We tested whether the combination of 4 established cell cycle regulators (p53, pRB, p21 and p27) could improve the ability to predict clinical outcomes in a large multi-institutional collaboration of patients with pT3-4N0 or pTany Npositive urothelial carcinoma of the bladder. We also assessed whether the combination of molecular markers is superior to any individual biomarker. Materials and Methods: The study comprised 692 patients with pT3-4N0 or pTany Npositive urothelial carcinoma of the bladder treated with radical cystectomy and bilateral lymphadenectomy (median followup 5.3 years). Scoring was performed using advanced cell imaging and color detection software. The base model incorporated patient age, gender, stage, grade, lymphovascular invasion, number of lymph nodes removed, number of positive lymph nodes, concomitant carcinoma in situ and adjuvant chemotherapy. Results: Individual molecular markers did not improve the predictive accuracy for disease recurrence and cancer specific mortality. Combination of all 4 molecular markers into number of altered molecular markers resulted in significantly 1 higher predictive accuracy than any single biomarker (p < 0.001.). Moreover addition of number of altered molecular markers to the base model significantly improved the predictive accuracy for disease recurrence (3.9%, p < 0.001) and cancer specific mortality (4.3%, p < 0.001). Addition of number of altered molecular markers retained statistical significance for improving the prediction of clinical outcomes in the subgroup of patients with pT3N0 (280), pT4N0 (83) and pTany Npositive (329) disease (p < 0.001). Conclusions: While the status of individual molecular markers does not add sufficient value to outcome prediction in patients with advanced urothelial carcinoma of the bladder, combinations of molecular markers may improve molecular staging, prognostication and possibly prediction of response to therapy.

Laparoscopic Enucleation of Liver Tumors. Corkscrew Technique Revisited

Background: Enucleation of small lesions located near the hepatic surface can be achieved with low morbidity and mortality. This article describes a simple laparoscopic technique for enucleation of liver tumors. Methods: After inspection and intraoperative ultrasonography, Glisson`s capsule is marked with eletrocautery 2 cm away from the tumor margin. Ultrasonography is used to ascertain surgical margin right before liver transection. Hemihepatic ischemia is applied and marked area is anchored by stitches. The suture is held together by metallic clips and upward traction is performed, facilitating the transection of the parenchyma and correct identification of vascular and biliary structures. Results: This technique has been successfully employed in six consecutive patients. There were four men and two women, mean age 50.3 years. Four patients underwent liver resection for malignant disease and two for benign liver neoplasm. Pathologic surgical margins were free in all cases and mean hospital stay was 2 days. No postoperative mortality was observed. Conclusion: This technique may facilitate laparoscopic nonanatomical liver resection and reduce risk of positive surgical margins. It is also useful in combination with anatomical laparoscopic liver resections such as right or left hemihepatectomies in patients with bilateral liver tumors as occurred in one of our patients.

Study into the use of continuous positive airway pressure in obstructive sleep apnoea-hypopnoea syndrome patients with daytime drowsiness

Background: Obstructive sleep apnoea-hypopnoea syndrome (OSAHS) is a respiratory disorder with high morbidity and mortality. Continuous positive airway pressure (CPAP) is the most commonly prescribed conservative treatment for adults with OSAHS. CPAP therapy normalises or decreases OSAHS symptoms and can reduce and prevent OSAHS complications. Aims: To evaluate adherence to nasal CPAP treatment and CPAP impact on daytime drowsiness. Method: A sample of 20 patients evaluated for daytime drowsiness using the Epworth sleepiness scale and interviewed for adherence to nasal CPAP use. Results: There was a significant decrease in the level of daytime sleepiness of the patients users of nasal CPAP (p=0.017); patients not using nasal CPAP experienced a decrease without statistical significance (p=0.162). 100% of CPAP users reported benefits and 50% of these reported related discomforts. Conclusions: Patients with OSAHS that use CPAP have a greater reduced level of sleepiness than those who do not use it.

Comparative neuroanatomical and temporal characterization of FluoroJade-positive neurodegeneration after status epilepticus induced by systemic and intrahippocampal pilocarpine in Wistar rats

The aims of this study were to characterize the spatial distribution of neurodegeneration after status epilepticus (SE) induced by either systemic (S) or intrahippocampal (H) injection of pilocarpine (PILO), two models of temporal lobe epilepsy (TLE), using FluoroJade (FJ) histochemistry, and to evaluate the kinetics of FJ staining in the H-PILO model. Therefore, we measured the severity of behavioral seizures during both types of SE and also evaluated the FJ staining pattern at 12, 24, and 168 h (7 days) after the H-PILO insult. We found that the amount of FJ-positive (FJ+) area was greater in SE induced by S-PILO as compared to SE induced by H-PILO. After SE induced by H-PILO, we found more FJ+ cells in the hilus of the dentate gyrus (DG) at 12 h, in CA3 at 24 h, and in CA1 at 168 h. We found also no correlation between seizure severity and the number of FJ+ cells in the hippocampus. Co-localization studies of FJ+ cells with either neuronal-specific nuclear protein (NeuN) or glial fibrillary acidic protein (GFAP) labeling 24 h after H-PILO demonstrated spatially selective neurodegeneration. Double labeling with FJ and parvalbumin (PV) showed both FJ+/PV+ and FJ+/PV- cells in hippocampus and entorhinal cortex, among other areas. The current data indicate that FJ+ areas are differentially distributed in the two TLE models and that these areas are greater in the S-PILO than in the H-PILO model. There is also a selective kinetics of FJ+ cells in the hippocampus after SE induced by H-PILO, with no association with the severity of seizures, probably as a consequence of the extra-hippocampal damage. These data point to SE induced by H-PILO as a low-mortality model of TLE, with regional spatial and temporal patterns of FJ staining. (C) 2010 Elsevier B.V. All rights reserved.

The role of tumor hypoxia in MUC1-positive breast carcinomas

Mucin 1 (MUC1) is a glycoprotein that is expressed on apical cell membranes in a variety of normal tissues. MUC1 is involved in cell signaling, inhibition of cell-cell and cell matrix adhesion, apoptosis, proliferation, and transcription. Hypoxia is an important factor that promotes cancer metastasis and stimulates angiogenesis and tumor progression. Hypoxia inducible factor 1 (HIF-1 alpha) and carbonic anhydrase IX (CAIX) are two molecules that are involved in this process. The role of hypoxia in MUC1+ invasive ductal breast carcinomas is not well established. In this study, the expression of MUC1 was correlated with the hypoxia-associated markers HIF-1 alpha and CAIX, as well as several immunohistochemical markers and clinicopathologic features of prognostic significance in 243 invasive ductal carcinomas. MUC1 was overexpressed in 37.0% of patients and correlated with the expression of estrogen receptor (p = 0.0001), progesterone receptor (p = 0.0001), HIF-1 alpha (p = 0.006), VEGF (p = 0.024), and p53 (p = 0.025). In breast cancer, MUC1 expression has been associated with increased degradation of inhibitor of NF-kappa B (I kappa B alpha), driving NF-kappa B to the nucleus and blocking apoptosis and promoting cell survival. We analyzed NF-kappa B expression in MUC1+ breast carcinoma and found a very significant relationship between these proteins (p = 0.0001). Our findings indicate that MUC1 may play a role in the regulation of hormone receptors by increasing the inactivation of p53 and targeting NF-kappa B to the nucleus. Our data also support the notion that activation of HIF-1 alpha in MUC1+ breast carcinomas may modulate VEGF expression, allowing a metabolic adaptation to hypoxia.

Positive impact of omega-3 fatty acid supplementation in a dog with drug-resistant epilepsy: A case study

Epilepsy is the most common neurological disorder in both dogs and humans. Although the pharmacological options for treatment of epilepsies have increased. it has been reported that two-thirds of dogs with epilepsy are refractory to antiepileptic drug therapy. To our knowledge, there are no experimental Studies in the literature that show an effect of omega-3 supplementation oil epilepsy in dogs. Our case study describes the effectiveness of daily intake of a moderate amount of fish oil in a case of canine epilepsy. (C) 2009 Elsevier Inc. All rights reserved.

In vitro analysis of inhibitory effects of the antibacterial monomer MDPB-containing restorations on the progression of secondary root caries

Objective: This study aimed to analyze in vitro inhibitory effects of restorative materials containing the antibacterial monomer 12-methacryloyloxydodecylpyridinium bromide (MDPB) on the formation of artificial secondary root caries lesions. Methods: Class V cavities (2 mm x 2 mm) were prepared in 75 human root fragments. Specimens were randomly divided into five groups (n = 15 fragments per group) and restored as follows: (I) MDPB-free adhesive system + MDPB-free composite (negative control); (II) resin modified glass ionomer (RM-GIC; positive control); (III) MDPB-free adhesive system + MDPB-containing composite (2.83% MDPB); (IV) MDPB-containing adhesive system + MDPB-free composite; M MDPB-containing adhesive system + MDPB-containing composite. Artificial secondary root caries lesions were produced by a biological artificial caries challenge. The restored specimens were immersed into a culture medium containing Streptococcus mutans and sucrose for 15 days. Histological slices (80 +/- 20 mu m) of the specimens were used for measuring the mean depths of the artificial lesions produced in both margins of the restorations using polarized light microscopy. Results were expressed in percentage related to the mean depth of the negative control, considered 100%. Data were compared by ANOVA followed by the Tukey`s test (p <= 0.05). Results: The depths of lesions adjacent to cavities filled with RM-GIC (GII; 85.17 +/- 15.2%) were significantly (p < 0.01) shallower than those adjacent to restorations with MDPB-free composite (GI; 100.00 +/- 10.04%), despite the presence of MDPB in the adhesive system (GIV; 101.95 +/- 21.32%). The depths of lesions adjacent to cavities restored with MDPB-containing composite (GIII; 82.68 +/- 12.81% and GV; 85.65 +/- 15.42%), despite the adhesive system used, were similar to those of RM-GIC (GII). Mean lesions depths in these groups decreased from 13% (GV) to 17% (GIII) in relation to the negative control (GI). Conclusions: MDPB-containing composite inhibits the progression of artificial secondary root caries lesions regardless of adhesive systems. (C) 2009 Elsevier Ltd. All rights reserved.