p53 and skin carcinomas with skull base invasion: a case-control study.

BACKGROUND: Some skin carcinomas may be very aggressive. Increased expression of the protein p53 has been associated with tumor aggressiveness. In this study, p53 expression was evaluated in basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) with skull base invasion, and was compared to tumors with good outcome. STUDY DESIGN AND SETTING: Expression of p53 was immunohistochemically analyzed and it was reported as present or absent in 24 BCC and 11 SCC with skull base invasion. Control group (good outcome) included 23 BCC and 10 SCC. RESULTS: Expression of p53 was noted in 70.83% of BCC with skull base invasion, compared to 43.48% in the control group (P = 0.058). Regarding SCC, p53 positivity was noted in only 9.09% of SCC with skull base invasion, compared to 40.00% in the control group (P = 0.149). CONCLUSIONS: In this study, p53 expression was more common among BCC with skull base invasion, compared to controls with good outcome, and the difference was considered marginally significant. This proportion was reversed in SCC, but the difference was not statistically significant. EBM rating: B-3b.     

Relationship between maternal- and fetal-specific IgE

AIM: A positive correlation between maternal and cord-blood IgE levels is well documented for total IgEs, but not for specific IgEs. The difficulty in detecting specific cord-blood IgEs is due to their low concentrations, which hinder their dosage by low-sensitivity methods. The study aimed to correlate maternal and foetal specific IgEs against individual cow's milk proteins, detected by highly sensitive and specific techniques. METHODS: Cow's milk specific IgE detection was performed by chemiluminescence on 52 specimens of maternal and cord blood after cow's milk protein separation by 1D and 2D gel electrophoresis. Cow's milk protein (CMP) antigens were identified by mass spectrometry techniques. RESULTS: Specific IgEs for CMPs were found in 25/52 (48.1%) of maternal sera and in 19/52 (37%) of cord-blood sera. In order of decreasing frequency, the proteins found were BSA, IgG heavy chain, caseins and, in a single case, b-lactoglobulin. Positive cord-blood sera in all cases corresponded to a positive maternal result, and maternal and foetal immunoreactivity patterns were closely correlated. Moreover, in no case was there a positive cord-blood response with a negative maternal response. CONCLUSION: The study demonstrates a close relationship between maternal and cord-blood specific IgE patterns. The phenomenon observed could provide a model to elucidate the general production method of foetal IgEs, which might only be produced in the presence of both the corresponding maternal IgE and the related allergen.     

Sleep disorders in women: clinical evidence and treatment strategies.

Sleep disorders are more prevalent in women than in men. Sex hormones modulate sleep-wake behaviors and mood and may contribute to heightened risk across the life cycle of women. Sleep disorders may have a unique expression in women, emerging throughout their reproductive life cycle. These conditions require careful treatment strategy to manage medical, hormonal, and behavioral contributing factors to poor sleep efficiency and impaired quality of life. This review focuses on clinical evidence for sleep disorders in women and discusses existing evidence of risk factors and treatment options for insomnia and sleep-disordered breathing in women.     

The effect of oral appliance therapy on blood pressure in patients with obstructive sleep apnea

The objective of the study was to investigate the effects of oral appliance (OA) therapy on ambulatory blood pressure in patients with obstructive sleep apnea (OSA). Eleven OSA patients who received OA therapy were prospectively investigated. Ambulatory blood pressure was measured for 20 h from 4:00 p.m. to 12:00 noon the next day using an ambulatory blood pressure monitor. The Respiratory Disturbance Index (RDI) was measured in the pretreatment and posttitration periods. The OA was titrated to reach a therapeutic jaw position over 2 to 8 months, and posttitration measurements were repeated. At posttitration, the RDI was significantly decreased from a mean (SD) of 24.7 (20.1) to 6.1 (4.5). Significant reductions in diastolic blood pressure (DBP) and mean arterial pressure (MAP) were found for the 20-h periods, and systolic blood pressure (SBP), DBP, and MAP while asleep. The mean values were 79.5 (5.5) to 74.6 (6.0) for DBP and 95.9 (5.4) to 91.2 (5.9) for MAP, for over a 20-h period, and 118.4 (10.0) to 113.7 (9.1) for SBP, 71.6 (8.0) to 67.2 (7.9) for DBP, and 88.4 (8.0) to 83.9 (7.5) for MAP, while asleep. This study suggests that successful OSA treatment with an OA may also be beneficial to lower blood pressure in OSA patients, as previously suggested for nasal continuous positive airway pressure therapy. This study was conducted in the Division of Orthodontics, The University of British Columbia, Canada     

Selecting antibodies to detect HER2 overexpression by immunohistochemistry in invasive mammary carcinomas.

There is an increasing clinical demand for HER2 analysis in breast cancer, especially since the release of trastuzumab. The authors assessed the ability of immunohistochemistry to detect HER2 overexpression in invasive mammary carcinomas (IMC) using five antibodies. Paraffin-embedded samples of 86 IMCs (T2N0) were used to compare the immunohistochemical overexpression of HER2 using two polyclonal antibodies (HercepTest [DAKO] and A0485 [DAKO]) and three monoclonal antibodies (CB11 from two different laboratories, Biogenex and Novocastra, and 4D5 [Genentech]). All immunostainings were scored according to the FDA-approved HercepTest recommendations. The HercepTest-positive cases were compared with gene amplification by FISH (Oncor Inform, Ventana). The HercepTest was positive in 31 of the 86 cases (36.1%). The DAKO antibody A0485 was positive in 25 of the 66 (37.8%). Monoclonal antibody 4D5 was positive in only 15 of the 86 cases (17.4%). There was almost total agreement in results between the two CB11 antibodies: 25 of the 86 positive cases (29.1%). All cases positive for CB11 or 4D5 were HercepTest positive. Most of the HercepTest 2+ cases were negative when using either monoclonal antibody. FISH was positive in 19 of the 20 HercepTest 3+ cases and negative in 5 HercepTest 2+ cases. Three CB11-2+ cases showed no amplification by FISH. In three FISH-positive cases the immunohistochemistry showed no overexpression by all antibodies used. These findings suggest that immunohistochemistry may be used reliably as a primary methodology for evaluating HER2; however, the use of polyclonal antibodies may not be adequate to assess HER2 overexpression. CB11, regardless of the manufacturer (Biogenex or Novocastra), showed better concordance with FISH (kappa=0.83) than did the polyclonal antibodies.     

Frontal white matter volume and delta EEG sources negatively correlate in awake subjects with mild cognitive impairment and Alzheimer's disease.

OBJECTIVE: A relationship between brain atrophy and delta rhythmicity (1.5-4 Hz) has been previously explored in Alzheimer's disease (AD) subjects [Fernandez A, Arrazola J, Maestu F, Amo C, Gil-Gregorio P, Wienbruch C, Ortiz T. Correlations of hippocampal atrophy and focal low-frequency magnetic activity in Alzheimer disease: volumetric MR imaging-magnetoencephalographic study. Am J Neuroradiol. 2003 24(3):481-487]. In this study, we tested the hypothesis that such a relationship does exist not only in AD patients but also across the continuum of subjects with mild cognitive impairment (MCI) and AD. METHODS: Resting, eyes-closed EEG data were recorded in 34 MCI and 65 AD subjects. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were estimated by LORETA. Cortical EEG sources were correlated with MR-based measurements of lobar brain volume (white and gray matter). RESULTS: A negative correlation was observed between the frontal white matter and the amplitude of frontal delta sources (2-4 Hz) across MCI and AD subjects. CONCLUSIONS: These results confirmed for the first time the hypothesis that the sources of resting delta rhythms (2-4 Hz) are correlated with lobar brain volume across MCI and AD subjects. SIGNIFICANCE: The present findings support, at least at group level, the 'transition hypothesis' of brain structural and functional continuity between MCI and AD.     

Laparoscopic Deployment of Biliary Self-Expandable Metal Stent (SEMS) for One-Step Palliation in 23 Patients with Advanced Pancreatico-Biliary Tumors—a Pilot Trial

Background Exploratory laparoscopy is commonly undertaken in patients with highly suspicious biliary and pancreatic lesions to facilitate diagnosis and staging cancer is present. If an unresectable tumor is identified, a second endoscopic procedure may be required do deploy a self-expandable metal stent (SEMS) for palliation. As endoscopic retrograde cholangio pancreatography (ERCP) may be unsuccessful in up to 20% of patients, we evaluated the feasibility and safety of deployment of self-expandable metal stents at the same time as the initial laparoscopy. Patients and Methods A total of 23 eligible patients (8 male and 15 female) with malignant obstruction of the common bile duct underwent deployment of SEMS at laparoscopy. Primary outcome measure was the successful laparoscopic deployment of stent and secondary outcome measure was complications rates. Results Indications for stent deployment were unresectable pancreatic cancer in 18, cholangiocarcinoma in two, neuroendocrine tumor in one and ampullary adenocarcinoma in two patients. The median age was 73 years (range 49–93). Twenty-two of 23 stents were deployed successfully: 17 stents were deployed transcystically and five via a choledochotomy. Median times for laparoscopic exploration and SEMS deployment were 165 min (range 105–230) and 20 min (range 10–50), respectively. Pre- and post-procedures median total bilirubin were 9.4 mg/dl (range 5.4–17.5) and 4.0 (range 2.6–7.1). The median size of the pancreatic mass was 3 cm (range 2–5 cm) and that of the common bile duct (CBD) from 9.2 mm (range 7.2–17.4). The mean duration of laparoscopy was 170 min (range 120–230 min) and that for stent deployment 23 min (range 10–50 min). Complications included bleeding, obstruction, and wound infection. Bleeding occurred on day 7 in two patients and on day 30 in one patient; bleeding occurred at the gastrojejunal anastomosis site and was successfully treated with endoscopic hemostasis. A total of three stent obstructions were identified: one each at 60, 90, and 120 days follow-up. All complications were successfully managed endoscopically. There were a total of seven deaths, six as a result of progressive cancer and one of surgical wound infection and ensuing complications. Conclusion This study demonstrates that laparoscopic deployment of self-expandable metal bile duct stents is feasible and safe. This option appears to be a reasonable option in patients with inoperable malignant obstruction of the distal common bile duct.     

Histopathological effects of [D-Leu]Microcystin-LR variants on liver, skeletal muscle and intestinal tract of Hypophthalmichthys molitrix (Valenciennes, 1844)

This study evaluated the effects of [D-Leu¹]Microcystin-LR variants, by the exposure of Hypophthalmichthys molitrix to Microcystis aeruginosa NPLJ4. Fish was placed in aquariums and exposed to 10⁵ cells mL⁻¹. For 15 days, 05 individuals were removed every 05 days, and tissue samples of liver, skeletal muscle and intestinal tract were collected for histopathologic analyses. Following exposure, those surviving were placed in clean water for 15 days to evaluate their recovery. A control without toxins was maintained in the same conditions and exhibited normal histology and no tissue damage. In exposed fish, samples were characterized by serious damages that similarly affected the different organs, such as dissociation of cells, necrosis and haemorrhage. Samples showed signs of recovery but severe damages were still observed. The results should be valuable to analyze the potency of microcystin toxicity and to help in the diagnosis of fish deaths.