Insulin reduces the BOLD response but is without effect on the VEP during presentation of a visual task in humans.

Functional magnetic resonance imaging (fMRI) based on blood oxygen level-dependent (BOLD) contrast has become an invaluable tool in the assessment of in vivo neuronal activation. Quantification of the BOLD response is determined by the hemodynamic and metabolic changes that occur in response to brain stimulation. However, these changes may vary by changes in insulin, a hormone known to be vasoactive in some tissues. To determine if insulin has an effect on fMRI, we measured the BOLD response to a visual stimulus in five normal volunteers in which insulin was first suppressed and then brought to a high physiological concentration. In addition, we also examined the effect of insulin on activation of the visual cortex as measured by the visual-evoked potential (VEP). We found that the BOLD response measured in the presence of insulin (serum insulin=236+/-29 pmol/L) was significantly lower (P<0.001) than that measured in its absence (serum insulin=8+/-2 pmol/L). Insulin was without effect on P100 amplitude or latency acquired in the presence or absence of insulin in 28 subjects using the same stimulus as that used for the fMRI experiments. Our observations suggest that insulin may have effects on cerebral blood flow and/or metabolism that affect the BOLD signal that are independent of its effects on neuronal activation identified by event related potentials (ERP). These findings highlight the complexity that must be considered when interpreting differences in fMRI responses between groups of subjects that differ in insulin concentration and/or insulin sensitivity.     

Positive estrogen receptor status is a poor prognostic factor in node-negative breast cancer: An observational study in Asian patients

This study evaluated the outcomes and prognostic factors for breast cancer according to initial lymph node (LN) status. Among patients with LN-negative breast cancer, we also focused on the prognostic value of estrogen receptor (ER) status.Medical records were retrospectively reviewed for 715 patients who underwent curative surgery for breast cancer between January 2005 and December 2015 at a single Korean institution. We evaluated factors that were associated with metastasis-free survival (MFS) according to LN status.Among the 715 patients (age: 28–87 years), 458 patients (64.1%) did not have axillary LN metastasis. Relative to patients without LN metastasis, patients with LN metastasis had larger tumor sizes and higher histological grades. Among patients with no LN metastasis, ER positivity was associated with non-significantly poorer MFS than ER negativity (mean survival: 138.90 months vs. 146.99 months, p = .17), and patients with LN-negative ER-positive disease had MFS rates of 91.7% at 5 years and 74.5% at 10 years. Among patients with LN-negative ER-positive disease, a poor prognosis was significantly associated with larger tumor size (≥2 cm, P = .03) and older age (≥50 years, P = .03).These results indicate that the risk of metastasis increases over time for patients with LN-negative ER-positive breast cancer, and especially for older patients or patients with larger tumors.     

Beta-blockers for the treatment of problematic hemangiomas

OBJECTIVE:

To examine treatment indications, efficacy and side effects of oral beta-blockers for the treatment of problematic hemangiomas.

METHODS:

A retrospective review of patients with hemangiomas presenting to the Alberta Children’s Hospital Vascular Birthmark Clinic (Calgary, Alberta) between 2009 and 2011 was conducted. The subset of patients treated with oral beta-blockers was further characterized, investigating indication for treatment, response to treatment, time to resolution of indication, duration of treatment, occurrence of rebound growth and side effects of therapy.

RESULTS:

Between 2009 and 2011, 311 new patients with hemangiomas were seen, of whom 105 were treated with oral beta-blockers. Forty-five patients completed beta-blocker treatment while the remainder continue to receive therapy. Indications for treatment were either functional concerns (68.6%) or disfigurement (31.4%). Functional concerns included ulceration (29.5%), periocular location with potential for visual interference (28.6%), airway interference (4.8%), PHACES syndrome (3.8%), auditory interference (0.95%) and visceral location with congestive heart failure (0.95%). The median age at beta-blocker initiation was 3.3 months; median duration of therapy was 10.6 months; and median maximal treatment dose was 1.5 mg/kg/day for propranolol and 1.6 mg/kg/day for atenolol. Ninety-nine patients (94.3%) responded to therapy with size reduction, colour changes, softened texture and/or healing of ulceration. Rebound growth requiring an additional course of therapy was observed in 23 patients. Side effects from beta-blockers included cool extremities (26.7%), irritability (17.1%), lower gastrointestinal upset (14.3%), emesis (11.4%), hypotension (10.5%), poor feeding (7.6%), lethargy (4.8%), bronchospasm (0.95%) and rash (0.95%). Side effects did not result in complete discontinuation of beta-blocker treatment in any case; however, they prompted a switch to a different beta-blocker preparation in some cases. Resolution of the primary indication, requiring a median time of three months, occurred in 87 individuals (82.9%).

CONCLUSIONS:

Treatment of infantile hemangiomas with oral beta-blocker therapy is highly effective and well tolerated, with more than 94% of patients demonstrating a response to treatment and 90% showing resolution of the primary functional indication for treatment.     

Imaging findings of implanted absorbable mesh in patients with breast partial resection

PURPOSE: The author presents imaging findings of patients that underwent partial resection of the breast followed by absorbable mesh implantation. MATERIALS AND METHODS: Ultrasonographic (n = 18) and mammographic (n = 11) images of patients that had undergone absorbable mesh implantation after breast partial resection were reviewed retrospectively. Sequential changes of the lesions were analyzed in follow-up ultrasonographic examinations, focusing on the change of the size and pattern of the lesion. The presence of a mass, asymmetry, focal asymmetry, architectural distortion, and calcification were evaluated by mammography. Pathologic findings of the implanted mesh in available cases were analyzed. RESULTS: Ultrasonograms revealed a well-encapsulated anechoic lesion with (pattern 1, n = 11) or without (pattern 2, n = 5) internal isoechoic nodular portion, and a hyperechoic mass-like lesion without anechoic portion (pattern 3, n = 2). The mean length of the longest diameter decreased gradually as determined in follow-up examinations (3 months, 6.12 +/- 2.599cm; 6 months, 5.08 +/- 2.105cm; 12 months, 3.26 +/- 2.206cm). In mammograms, a mass (n = 4) was noted at the surgical site and focal asymmetry, overlapping with the postoperative change, was seen in the remaining seven cases. Pathologic findings of two cases revealed foreign body reaction. CONCLUSION: Ultrasonography of the patients that underwent breast partial resection followed by absorbable mesh implantation showed a well-encapsulated cyst at the surgical site that gradually decreased in follow-up examinations. Adjunctive ultrasonography combined with mammography would be recommended in postoperative follow-up examinations.     

Characteristics of a donor population in western Venezuela

To determine the characteristics of blood donors in western Venezuela, we collected data from 1983 to 1985 on 31,320 volunteer donors at the Blood Bank of the State of Zulia in Maracaibo. Fifty-nine percent of the donors were blood group O, 30 percent were group A, 9 percent were group B, and 2 percent were group AB. Most of the donors (93%) were Rh positive. One percent of donors had positive reactions to hepatitis B surface antigen, 3.15 percent for syphilis, 1.43 percent for antibodies to Trypanosoma cruzi, and 0.32 percent to human immunodeficiency virus antibodies. About one-half of the donors were between 18 and 30 years old, and only 10 percent were women. To determine if iron deficiency anemia was a cause for the small size of the female donor pool, we measured serum ferritin in 50 first-time female donors. Ten of these (20%) had serum ferritin values below normal, and the distribution of serum ferritin levels of all 50 was very similar to that reported for frequent donors in Europe and the United States, with a clustering of ferritin values between 10 and 70 ng per ml. The data indicate that blood donors in western Venezuela are markedly different from those in the United States and that iron supplementation may be indicated for female Venezuelan donors.     

Effects of vitamin E on oxidative stress and membrane fluidity in brain of streptozotocin-induced diabetic rats

Background: Diabetics and experimental animal models exhibit high oxidative stress due to persistent and chronic hyperglycemia, thereby deplete the activity of the antioxidative defense system and thereby promote the generation of free radicals. The current study examined the effects of vitamin E on oxidative stress and membrane fluidity in the brain of diabetes-induced rats. Methods: Sprague–Dawley male rats were randomly assigned to normal and streptozotocin (STZ)-induced diabetic groups. The diabetic groups were fed a vitamin E-free diet, 40 mg vitamin E/kg diet, or 400 mg vitamin E/kg diet. Diabetes was induced with STZ after 3 weeks of the experimental diet, then the rats were sacrificed 9 days later to determine the oxidative stress and cell membrane fluidity in the brain. Results: Dietary vitamin E strengthened the antioxidative defense system with an increased activity of the antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) and increased vitamin E content, in the brain of the diabetes-induced exeperimental rats. Accordingly, vitamin E was found to reduce the accumulation of reactive oxygen species (ROS), such as superoxide radical decrease the generation of oxidative damage substances, such as the carbonyl value, increase the membrane fluidity lowered by oxidative damage, and significantly improve the lipid composition. Conclusions: Vitamin E was found to be excellent for strengthening the antioxidative defense system, reducing the generation of ROS and damaging oxidative substances, and maintaining membrane fluidity in the brain of diabetes-induced rats.     

Evidence for neuroprotective effect of sulbutiamine against oxygen-glucose deprivation in rat hippocampal CA1 pyramidal neurons

Hippocampus is one of the earliest brain regions that gets affected by ischemia, however, no pharmacological therapy exists yet that can fully counteract the ischemic damage. Here we study the effect of sulbutiamine, a synthetic thiamine analogue that can cross the blood-brain barrier easily, on hippocampal neurons under an in vitro model of ischemia, oxygen-glucose deprivation (OGD). We find that exposure to OGD in the presence of sulbutiamine significantly increases neuronal viability and enhances electrophysiological properties such as excitatory synaptic transmissions and intrinsic neuronal membrane input resistance in a concentration-dependent manner. Overall, here we report, for the first time, the neuroprotective evidence of sulbutiamine on hippocampal CA1 pyramidal neurons under OGD, which may have beneficial implications as a possible therapeutic agent/substance against ischemic insult.     

Value of contrast-enhanced power Doppler sonography using a microbubble echo-enhancing agent in evaluation of small breast lesions

PURPOSE: The purpose of this study was to prospectively evaluate the usefulness of contrast-enhanced power Doppler sonography (PDUS) using a microbubble echo-enhancing agent in differentiating between malignant and benign small breast lesions. PATIENTS AND METHODS: Between July 1, 2000, and September 30, 2001, we performed gray-scale sonographic examination of patients in whom diagnostic sonography or screening mammography had revealed solid breast lesions measuring less than 2 cm in the largest dimension. The patients were then examined on PDUS before and after injection of a microbubble contrast agent. The sonographic findings for all 3 techniques, as well as the morphologic features of the Doppler signals for each patient before and after injection of the contrast agent on PDUS, were independently assessed. Each lesion was classified as "benign" or "malignant" on the basis of specific criteria for sonographic interpretation. A hemodynamic study was performed in which time-transit profiles of the Doppler signals on contrast-enhanced PDUS were generated using a computer-assisted program, and the results for each patient were compared with the findings of a histopathologic examination of surgical specimens. RESULTS: Thirty-six patients (35 women and 1 man) with a mean age of 43.5 years (range, 18-69 years) were evaluated. The tumors ranged from 4 to 19 mm in the largest dimension. Histopathologic examination revealed that 19 tumors were benign and 17 were malignant. For morphologic diagnosis of the malignant lesions, the sensitivity of gray-scale sonography was 100%, compared with 29% for PDUS without contrast enhancement. The specificity of gray-scale sonography was 47%, compared with 74% for PDUS without contrast enhancement. Contrast-enhanced PDUS had a sensitivity of 71% and a specificity of 58%. The diagnostic accuracy was 72% for gray-scale sonography, 53% for PDUS without contrast enhancement, and 64% for contrast-enhanced PDUS. The time-transit profiles of the hemodynamic study did not reveal a statistically significant difference in the accuracy rates of contrast-enhanced PDUS between benign and malignant breast lesions. CONCLUSIONS: Compared with PDUS without contrast enhancement, contrast-enhanced PDUS provides better visualization of the morphology of vascular Doppler signals that is characteristic of malignancy and therefore has a higher sensitivity and diagnostic accuracy, albeit a lower specificity. In differentiating between benign and malignant small breast lesions, contrast-enhanced PDUS can be helpful when used with gray-scale sonography and PDUS without contrast enhancement.