An automated procedure for the assessment of white matter hyperintensities by multispectral (T1, T2, PD) MRI and an evaluation of its between-centre reproducibility based on two large community databases

Introduction An automated procedure for the detection, quantification, localization and statistical mapping of white matter hyperintensities (WMH) on T2-weighted magnetic resonance (MR) images is presented and validated based on the results of a between-centre reproducibility study. Methods The first step is the identification of white matter (WM) tissue using a multispectral (T1, T2, PD) segmentation. In a second step, WMH are identified within the WM tissue by segmenting T2 images, isolating two different classes of WMH voxels – low- and high-contrast WMH voxels, respectively. The reliability of the whole procedure was assessed by applying it to the analysis of two large MR imaging databases (n = 650 and n= 710, respectively) of healthy elderly subjects matched for demographic characteristics. Results Average overall WMH load and spatial distribution were found to be similar in the two samples, (1.81 and 1.79% of the WM volume, respectively). White matter hyperintensity load was found to be significantly associated with both age and high blood pressure, with similar effects in both samples. With specific reference to the 650 subject cohort, we also found that WMH load provided by this automated procedure was significantly associated with visual grading of the severity of WMH, as assessed by a trained neurologist. Conclusion The results show that this method is sensitive, well correlated with semi-quantitative visual rating and highly reproducible.     

Vertical Scar Mammaplasty in Gigantomastia: Retrospective Study of 115 Patients Treated Using the Modified Lejour Technique

Since 1996, the original technique of superior pedicle vertical scar mammaplasty described by Lejour has been modified by decreasing skin and glandular undermining, limiting liposuction, avoiding tight glandular stitches, and adding a small horizontal scar for very large breasts. Between 1996 and 2002, 115 consecutive patients underwent a bilateral reduction mammaplasty of more than 500 g per breast using the modified Lejour technique. The early, late, and delayed complications were studied according to four parameters: glandular resection, age, smoking habits, and body mass index (BMI). There was no difference in terms of complications according to the glandular resection. Patients with a high BMI were found to have a higher rate of wound dehiscence. The occurrence of partial areolar necrosis proved to be related to smoking habits. Patients younger than 20 years presented a lower rate of seroma. The modified Lejour technique has proved to be safe and effective for large breasts.     

Challenges of Implementing Depression Care Management in the Primary Care Setting

Empirical evidence shows that care management is an effective tool for improving depression treatment in primary care patients. However, several conceptual and practical issues have not been sufficiently addressed. This article explores questions concerning the scope of care management services within the chronic illness care model; optimal ways to identify depressed patients in the primary care setting; responsibilities and desirable qualifications of depression care managers; the location and manner in which care managers interact with patients; costs of services provided by care managers; and the level of supervision by mental health specialists that is necessary to ensure quality care.     

Mary Glover Lecture 2006: the contributions of neuroscience nursing to the field of quality of life

The scholarly literature related to quality of life (QoL) is reviewed. Specific contributions by neurosciences nursing related to quality of life for patients and family caregivers is presented in the areas of stroke, neuro-oncology, traumatic brain injury, multiple sclerosis, and epilepsy. QoL information is important, as it is used in decisions concerning treatment and interventions for patients and their family members who are living with neurological conditions and their consequences.     

Using reagent-supported thromboelastometry (ROTEM((R))) to monitor haemostatic changes in congenital heart surgery employing deep hypothermic circulatory arrest

Objective: Cardiac surgery employing cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) can induce coagulation disturbances and bleeding complications that may be especially severe in infants. A better understanding of the coagulopathy and a quick method for its evaluation would be helpful in the management of patients exposed to CPB and DHCA. This study aimed to monitor coagulation defects in congenital heart surgery using rotational thromboelastometry (ROTEM((R))), standard coagulation tests and platelet flow cytometry. Methods: The study comprised 10 infants undergoing surgery for congenital heart disease on CPB and DHCA. Blood was sampled at skin incision, after heparinisation during CPB (directly pre- and directly post-DHCA) and after protamine administration post-CPB. ROTEM((R)) using different reagents including a heparinase-containing assay to evaluate coagulation during heparinisation, APTT and INR, and flow cytometry to evaluate platelet activation were performed. Results: During CPB, the ROTEM((R)) indicated CPB-induced clotting factor depletion and platelet dysfunction that persisted after CPB and heparin neutralisation. ROTEM((R)) results were available within 15min and therefore much faster than standard tests. ROTEM((R))-guided specific blood product treatment resulted in satisfactory coagulatory function. The highest degree of platelet activation was found directly after DHCA. Conclusions: A major benefit of ROTEM((R)) is the quick detection of a developing coagulopathy already during CPB. ROTEM((R)) guides quick and specific blood product treatment after CPB, which may decrease bleeding complications in cardiac surgery. The finding of maximal platelet activation directly after DHCA suggests that not only CPB but also hypothermia activates platelets in vivo, thereby contributing to platelet dysfunction.     

Use of amniotic membrane transplantation in the treatment of venous leg ulcers

Amniotic membrane (AM), the most internal placental membrane, has unique properties including antiadhesive effects, bacteriostatic, wound protection and pain-reduction properties, as well as epithelialization initialization capacities. Furthermore, AM is widely available and less costly than other bioengineered skin substitutes. In a prospective pilot study, we evaluated the safety, feasibility, and the effects on healing of AM graft in 15 patients with chronic venous leg ulcers. AM grafts were prepared from placentas harvested during cesarean section. All grafted AM had adhered to the wound bed 7 days after being applied with a 100% engraftment rate. The percentage of granulation tissue increased significantly (from 17% on day 0 to 69% on day 14, p<0.0001), along with a significant decrease of fibrinous slough (from 36% at day 0 to 16% at day 14, p<0.001). A significant clinical response occurred in 12 patients (80%) including complete healing (20%) in three during the 3-month follow-up period. The ulcer surface area decreased significantly from a mean value (+/- standard deviation) of 4.59 +/- 2.49 cm(2) at baseline to 2.91+/-2.01 cm(2) on day 30 (p<0.001). All patients experienced a significant reduction of ulcer-related pain rapidly after AM transplantation. No adverse events were recorded. AM transplantation seems to function as a safe substrate, promoting proper epithelialization while suppressing excessive fibrosis. Further advantages of biotherapy with AM are its easy and low-cost production, and that it can be applied as an ambulatory treatment without immobilization. AM transplantation may thus be considered to be an alternative method for treating chronic leg ulcers.     

Effects of sleeve gastrectomy in high fat diet-induced obese mice: respective role of reduced caloric intake,white adipose tissue inflammation and changes in adipose tissue and ectopic fat depots

Background

Sleeve gastrectomy (SG) has become a popular bariatric procedure. The mechanisms responsible for weight loss and improvement of metabolic disturbances have still not been completely elucidated. We investigated the effect of SG on body weight, adipose tissue depots, glucose tolerance, and liver steatosis independent of reduced caloric intake in high-fat-diet-induced obese mice.

Methods

C57BI/6 J mice fed a high fat diet (45 %) for 33 weeks were divided into three groups: sleeve gastrectomy (SG, 13 mice), sham-operated ad libitum fed (SALF, 13 mice) and sham-operated pair fed (PFS, 13 mice). The animals were humanely killed 23 days after surgery.

Results

In SG mice, food intake was reduced transiently, but weight loss was significant and persistent compared to controls (SG vs. PFS, P < 0.05; PFS vs. SALF, P < 0.05). SG mice showed improved glucose tolerance and lower levels of liver steatosis compared with controls (area under the curve, SG vs. PFS, P < 0.01; PFS vs. SALF, P < 0.05) (liver steatosis, SG vs. PFS, P < 0.05; PFS vs. SALF, P < 0.01). This was associated with a decrease in the ratios of the weight of pancreas, epididymal and inguinal adipose tissues to body weight, and an increase in the ratio of brown adipose tissue weight to body weight. Epididymal adipose tissue was also infiltrated by fewer activated T cells and by more anti-inflammatory regulatory T cells. Serum levels of fasting acyl ghrelin were still significantly decreased 3 weeks after surgery in SG mice compared to PFS mice (P < 0.05).

Conclusions

Reduced white adipose tissue inflammation, modification of adipose tissue development (brown vs. white adipose tissue), and ectopic fat are potential mechanisms that may account for the reduced caloric intake independent effects of SG.     

Regulation of aromatase activity of rat granulosa cells: induction of synthesis of NADPH-cytochrome P-450 reductase by FSH and dibutyryl cyclic AMP

Aromatase is an enzyme complex that is composed of a specific form of cytochrome P-450 and a flavoprotein, NADPH-cytochrome P-450 reductase. Aromatase activity of granulosa cells is increased markedly by follicle-stimulating hormone (FSH) and by analogs of cyclic AMP. It was the objective of the present study to investigate the effects of FSH and dibutyryl cyclic AMP (Bt₂cAMP) on the synthesis of NADPH-cytochrome P-450 reductase in rat granulosa cells maintained in vitro. Granulosa cells were obtained from the ovaries of diethylstilbestrol (DES)-treated immature rats and were incubated in the presence of DES (10⁻⁷ M), DES + FSH (250 ng/ml), or DES + Bt₂cAMP (1 mM) for up to 72 h. After 72 h of incubation, aromatase activity of cells incubated with DES alone was 5 pmoles estrogen formed 2 h⁻¹ mg⁻¹ protein and was increased > 60-fold in cells incubated with FSH or Bt₂cAMP. NADPH-cytochrome P-450 reductase was immunoisolated from [³⁵S]methionine-labeled lysates of granulosa cells incubated for 72 h in the absence or presence of stimulatory factors. The rate of synthesis of reductase was found to be increased about 3-fold in cells incubated with DES + FSH or DES + Bt₂cAMP as compared to cells incubated with DES alone. By immunoblot analysis we found that the cellular content of reductase was increased about 2-fold by FSH and Bt₂cAMP treatment. Reductase specific activity was 10 nmoles min⁻¹ mg⁻¹ protein in membrane fractions of DES-treated cells and was increased 1.6-fold by FSH treatment. These findings are indicative that FSH increases the rate of synthesis, cellular content and specific activity of NADPH-cytochrome P-450 reductase in rat granulosa cells in vitro. The finding that Bt₂cAMP causes a similar induction of reductase synthesis is suggestive that the stimulatory effect of FSH on this component of the aromatase enzyme complex is mediated by an increase in cyclic AMP formation.     

Consequences of lipid droplet coat protein downregulation in liver cells: abnormal lipid droplet metabolism and induction of insulin resistance

OBJECTIVE—Accumulation of intracellular lipid droplets (LDs) in non-adipose tissues is recognized as a strong prognostic factor for the development of insulin resistance in obesity. LDs are coated with perilipin, adipose differentiation–related protein, tail interacting protein of 47 kd (PAT) proteins that are thought to regulate LD turnover by modulating lipolysis. Our hypothesis is that PAT proteins modulate LD metabolism and therefore insulin resistance.RESEARCH DESIGN AND METHODS—We used a cell culture model (murine AML12 loaded with oleic acid) and small interfering RNA to directly assess the impact of PAT proteins on LD accumulation, lipid metabolism, and insulin action. PAT proteins associated with excess fat deposited in livers of diet-induced obese (DIO) mice were also measured.RESULTS—Cells lacking PAT proteins exhibited a dramatic increase in LD size and a decrease in LD number. Further, the lipolytic rate increased by ∼2- to 2.5-fold in association with increased adipose triglyceride lipase (ATGL) at the LD surface. Downregulation of PAT proteins also produced insulin resistance, as indicated by decreased insulin stimulation of Akt phosphorylation (P < 0.001). Phosphoinositide-dependent kinase-1 and phosphoinositide 3-kinase decreased, and insulin receptor substrate-1 307 phosphorylation increased. Increased lipids in DIO mice livers were accompanied by changes in PAT composition but also increased ATGL, suggesting a relative PAT deficiency.CONCLUSIONS—These data establish an important role for PAT proteins as surfactant at the LD surface, packaging lipids in smaller units and restricting access of lipases and thus preventing insulin resistance. We suggest that a deficiency of PAT proteins relative to the quantity of ectopic fat could contribute to cellular dysfunction in obesity and type 2 diabetes.The surge in obesity predicts a further increase in associated complications, insulin resistance, diabetes, and heart disease (1,2). Increased fatty acid availability in obesity is associated with accumulation of ectopic fat, mainly in the form of triacylglyerol (TAG) (3). Although ectopic fat correlates with systemic and tissue insulin resistance (4–6), a number of circumstances are known in which high tissue lipid stores are not associated with insulin resistance. Endurance-trained athletes have high intramyocellular lipids yet are highly insulin sensitive. Importantly, the size and intracellular distribution of lipid droplets (LDs) differs in muscle from insulin-sensitive athletes compared with insulin-resistant patients (7). Thus, the negative consequences of high cellular lipids may be related to the ability of the cell to regulate lipid storage and utilization.LDs are energy-storage organelles but have a surprisingly complex function in lipid homeostasis. LD biogenesis is a fundamental cellular function; when exposed to nonesterified fatty acids (NEFAs), cells store them as TAG in LDs (8). Such LD accumulation maintains low intracellular NEFAs, avoiding their toxic effects on cellular physiology while supporting cellular needs by releasing NEFAs for use in β-oxidation and membrane synthesis. LDs’ function to sequester and release NEFAs is thus critical for proper cellular function. Nonadipogenic tissues in patients with metabolic syndrome are exposed to chronically elevated serum levels of NEFAs, and these tissues respond by LD accumulation. Such ectopic fat deposition protects from NEFA-mediated lipotoxicity (9), but in patients with metabolic syndrome the LD is inadequate to prevent pathological consequences. An important question arises: what molecular mechanisms regulate lipid storage in nonadipogenic tissues?To date, we have only limited information on nonadipose LDs. Recent studies (10,11) identified a proteomic “signature,” consistently including at least one member of the PAT protein family: perilipin, adipose differentiation–related protein (ADFP), tail interacting protein of 47 kDa (Tip47), S3–12, and lipid dosage droplet protein-5 (LSDP-5). Despite tissue dependence, the ubiquitous nature of the family suggests an important role in LD machinery. ADFP, Tip47, and LSDP-5 are broadly distributed, notably in nonadipogenic liver and muscle tissues that do not express perilipin (13,24). Our hypothesis is that saturation of nonadipogenic tissue''s capacity to appropriately regulate storage and release of NEFAs via LDs results from variations in the expression and/or activity of PAT proteins. To study functional consequences of downregulating two major PAT proteins, ADFP and Tip47, on insulin resistance and lipid metabolism, we used small interfering RNA (siRNA) in a cell culture model. To assess the in vivo relevance of this finding, we measured the expression of PAT proteins associated with excess lipids accumulated in the livers of high-fat–fed obese mice.     

Evaluating peer support for prostate cancer: the Prostate Cancer Peer Support Inventory

OBJECTIVE: To develop and test a measure for assessing peer support for men attending prostate cancer support groups, and to describe socio-demographic, medical and adjustment characteristics of Australian men who attend these support groups. PATIENTS AND METHODS: In all, 1224 men (51% response) from 44 prostate-cancer support groups across Australia were recruited by mail. Men completed self-report measures that included the Prostate Cancer Peer Support Inventory (PCSI), the UCLA Prostate Cancer Index bother scales, psychological distress, quality of life (QoL), bother from pain and tiredness, perception of the clinician's support for group participation. Group-level variables were also included in the analyses. RESULTS: Peer support was rated positively by most men; a high satisfaction with support groups was related to better QoL, lower pain, younger age, higher perceived clinician support for group participation, use of alternative therapies, lower education, and regular attendance; dissatisfaction with support groups was related to higher psychological distress, lower QoL, and lower perceived clinician support for group participation. Group variables did not predict positive or negative support. Overall QoL was similar to community norms and psychological distress was low, with only 8% of men reporting high distress. The most common physical symptom was sexual bother, with 74% of men reporting moderate or high bother. CONCLUSIONS: The PCSI was a useful measure of peer support. Perception of the benefits of peer support was related to individual but not group differences. The clinicians' attitudes to participation in support groups influenced the men's experience of these groups, and this finding has implications for developing support services for these men.