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.     

Sensitivity to acute insulin-mediated suppression of plasma free fatty acids is not a determinant of fasting VLDL triglyceride secretion in healthy humans

One important mechanism whereby obesity-associated insulin resistance leads to VLDL overproduction is thought to be by the increased flux of free fatty acids (FFAs) from extrahepatic tissues to liver, which arises as a direct consequence of impaired insulin action in adipose tissue and skeletal muscle. The aim of the present study was to address whether direct measures of peripheral tissue insulin sensitivity with regard to FFAs and glucose in the fasting state are good predictors of postabsorptive VLDL triglyceride secretion rate (VLDL-TG ASR) in humans, independent of obesity. Eighteen healthy control subjects, after an overnight fast, underwent three studies 3 weeks apart, in random order. Study 1: VLDL-TG levels, fractional clearance rate (per h), and VLDL-TG ASR were determined after an intravenous bolus of [1,1,2,3,3-(2)H(5)] glycerol. Study 2: Insulin sensitivity (S(I)), acute insulin response (AIR), and acute C-peptide response to glucose were assessed by frequently sampled intravenous glucose tolerance test using the minimal model approach. Study 3: Insulin-mediated suppression of plasma FFAs (k) and insulin clearance were assessed in response to a low-dose stepwise intravenous insulin infusion. BMI (R(2) = 0.54), AIR, and fasting insulin levels were positively and S(I) negatively correlated with VLDL-TG ASR, but there was no significant association with plasma FFAs or k. Only BMI remained significantly associated with VLDL-TG ASR in multivariate analysis. The best multivariate model for VLDL-TG ASR (R(2) = 0.61, P = 0.0008) included BMI (P = 0.0008) and S(I) (P = 0.12, inversely correlated). VLDL-TG secretion is predicted by BMI, independently of direct measures of insulin sensitivity. The sensitivity to insulin's acute suppressive effect on plasma FFA levels during fasting is not an important determinant of postabsorptive VLDL-TG secretion in humans.     

Immunoglobulin heavy chain transgenic mice expressing Galalpha(1,3)Gal-reactive antibodies

BACKGROUND: Natural antibodies that bind the carbohydrate antigen Galalpha1-3Galbeta1-4GlcNAc-R (alphaGal) mediate rigorous rejection of porcine xenografts and represent a major immunological hurdle to successful discordant xenotransplantation. However, little is known about how production of antibodies specific for alphaGal is regulated. METHODS: Transgenic mice expressing an IgM heavy chain isolated from a B-cell hybridoma that produces antibodies specific for alphaGal were constructed. These mice were bred to mutant mice that lack the alphaGal epitope (GT0 mice) or wild-type (GT+) mice to generate animals in which the transgene is expressed in the presence or absence of alphaGal as a "self"-antigen. Development of transgene-expressing B cells and production of alphaGal-specific serum antibodies were then analyzed in transgenic mice on GT0 and GT+ backgrounds. RESULTS: B cells expressing the transgenic heavy chain and transgene-encoded serum antibodies specific for alphaGal were readily detected in mice on the GT0 background. Most alphaGal-reactive antibodies in GT0 mice used the transgene rather than endogenous Ig heavy chains. In contrast, transgene-encoded serum antibodies specific for alphaGal were not detected in GT+ mice. In transgenic mice on the GT+ background, B cells expressing the transgene underwent deletion as a result of encountering alphaGal during their development, indicating that expression of alphaGal as part of self-mediated efficient negative selection of B cells expressing transgene-encoded alphaGal-specific antibodies. CONCLUSIONS: The development of transgenic mice expressing a B cell receptor specific for alphaGal provides a novel system to study developmental regulation of B cells making carbohydrate-specific antibodies. In addition, these mice may be useful for examining methods to prevent production of alphaGal-reactive antibodies.     

Increasing incidence of bilateral mastectomies: the patient perspective

Background

Numerous studies have reported increasing rates of contralateral prophylactic mastectomies (CPMs). Understanding patient rationale for the surgical choice may provide insight into this trend.

Methods

A questionnaire was mailed to 350 mastectomy patients identified from a community health system tumor registry.

Results

Two hundred fifty questionnaires were received; of these, 237 had undergone mastectomy. Fifty-two percent had unilateral mastectomy (UM), and 43% had bilateral mastectomies (BMs) (6% for bilateral disease). Women younger than 60 years of age were more likely to choose BM (P = .0046). Those who had CPM were significantly more likely to make the same surgical decision (P < .0001). Reconstruction was performed in 52%, with BM patients more likely to undergo reconstruction (P = .009). Twenty-three (19%) needed unanticipated reoperation for reconstruction complications. CPM had equivalent rates of unanticipated surgery versus UM (P = .64).

Conclusions

Patients choosing BMs are younger, have equivalent rates of reoperation because of reconstruction complications, and are significantly more satisfied with their decision than those who chose UM.     

Eleventh international Argos proceedings: critical decision making in degenerative spinal stenosis

The eleventh Argos international symposium was held on 25 and 26 January 2007 at Maison des Arts et Métiers, Paris. Regular attendees were present as well as newcomers from around the world.     

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.     

Surgery for small-bowel neuroendocrine tumors: Is there any benefit of the laparoscopic approach?

Background

Surgery of small-bowel neuroendocrine (SBNE) tumors is demanding because of the need for associated extensive node dissection and assessment of possible synchronous lesions. For this reason, possible benefit of laparoscopy in SBNE tumors has not been reported to date.

Methods

From 1996, all patients operated on in Beaujon Hospital for SBNE tumors were retrospectively extracted from a prospectively maintained database of intestinal resections.

Results

Overall, 73 patients [55 % males, median age 55 years (range 27–79)] underwent small bowel resection (n = 38; 54 %), ileocolectomy (n = 25; 36 %), or both (n = 7; 10 %). In 18 patients, resection of synchronous liver metastasis was performed simultaneously. Resection was performed laparoscopically in 12 patients (16 %). Resection was R0 in 40 patients (55 %), R1 in 1 patient (1 %), and R2 in 32 patients (44 %) because of unresectable liver metastases (n = 29), nodal involvement (n = 1), or both (n = 2). Laparoscopy was associated with similar R0 (p = 0.06) and morbidity (p = 0.95) rates, but a shorter hospital stay (p = 0.003) compared with laparotomy. Median follow-up was 39 months. Progression-free survival (PFS) at 1, 3, and 5 years were 95, 83 and 75 %, respectively, for R0 patients without liver metastasis; 92, 83, and 57 %, respectively, for R0 patients with resected liver metastasis; and 82, 58 and 30 %, respectively, for R2 patients (p = 0.045). Overall survival and PFS did not show any difference when comparing the laparoscopic and open groups.

Conclusion

Complete resection of primary SBNE tumors with or without liver metastasis is associated with good long-term survival. In selected patients, laparoscopy for SBNE tumors is feasible and associated with a shorter hospital stay than laparotomy.