Epidural extension failure in obese women is comparable to that of non-obese women.

BACKGROUND: Management of labor epidurals in obese women is difficult and extension to surgical anesthesia is not always successful. Our previous retrospective pilot study found epidural extension was more likely to fail in obese women. This study used a prospective cohort to compare the failure rate of epidural extension in obese and non-obese women and to identify risk factors for extension failure. METHODS: One hundred obese participants (Group O, body mass index ≥ 40 kg/m2 ) were prospectively identified and allocated two sequential controls (Group C, body mass index ≤ 30 kg/m2 ). All subjects utilized epidural labor analgesia and subsequently required anesthesia for cesarean section. The primary outcome measure was failure of the labor epidural to be used as the primary anesthetic technique. Risk factors for extension failure were identified using Chi-squared and logistic regression. RESULTS: The odds ratio (OR) of extension failure was 1.69 in Group O (20% vs. 13%; 95% CI: 0.88-3.21, P = 0.11). Risk factors for failure in obese women included ineffective labor analgesia requiring anesthesiologist intervention, (OR 3.94, 95% CI: 1.16-13.45, P = 0.028) and BMI > 50 kg/m2 (OR 3.42, 95% CI: 1.07-10.96, P = 0.038). CONCLUSION: The failure rate of epidural extension did not differ significantly between the groups. Further research is needed to determine the influence of body mass index > 50 kg/m2 on epidural extension for cesarean section.

A hybrid approach for fusing 4D-MRI temporal information with 3D-CT for the study of lung and lung tumor motion.

PURPOSE: Accurate visualization of lung motion is important in many clinical applications, such as radiotherapy of lung cancer. Advancement in imaging modalities [e.g., computed tomography (CT) and MRI] has allowed dynamic imaging of lung and lung tumor motion. However, each imaging modality has its advantages and disadvantages. The study presented in this paper aims at generating synthetic 4D-CT dataset for lung cancer patients by combining both continuous three-dimensional (3D) motion captured by 4D-MRI and the high spatial resolution captured by CT using the authors' proposed approach. METHODS: A novel hybrid approach based on deformable image registration (DIR) and finite element method simulation was developed to fuse a static 3D-CT volume (acquired under breath-hold) and the 3D motion information extracted from 4D-MRI dataset, creating a synthetic 4D-CT dataset. RESULTS: The study focuses on imaging of lung and lung tumor. Comparing the synthetic 4D-CT dataset with the acquired 4D-CT dataset of six lung cancer patients based on 420 landmarks, accurate results (average error <2 mm) were achieved using the authors' proposed approach. Their hybrid approach achieved a 40% error reduction (based on landmarks assessment) over using only DIR techniques. CONCLUSIONS: The synthetic 4D-CT dataset generated has high spatial resolution, has excellent lung details, and is able to show movement of lung and lung tumor over multiple breathing cycles.

A spatiotemporal-based scheme for efficient registration-based segmentation of thoracic 4-D MRI.

Dynamic three-dimensional (3-D) (four-dimensional, 4-D) magnetic resonance (MR) imaging is gaining importance in the study of pulmonary motion for respiratory diseases and pulmonary tumor motion for radiotherapy. To perform quantitative analysis using 4-D MR images, segmentation of anatomical structures such as the lung and pulmonary tumor is required. Manual segmentation of entire thoracic 4-D MRI data that typically contains many 3-D volumes acquired over several breathing cycles is extremely tedious, time consuming, and suffers high user variability. This requires the development of new automated segmentation schemes for 4-D MRI data segmentation. Registration-based segmentation technique that uses automatic registration methods for segmentation has been shown to be an accurate method to segment structures for 4-D data series. However, directly applying registration-based segmentation to segment 4-D MRI series lacks efficiency. Here we propose an automated 4-D registration-based segmentation scheme that is based on spatiotemporal information for the segmentation of thoracic 4-D MR lung images. The proposed scheme saved up to 95% of computation amount while achieving comparable accurate segmentations compared to directly applying registration-based segmentation to 4-D dataset. The scheme facilitates rapid 3-D/4-D visualization of the lung and tumor motion and potentially the tracking of tumor during radiation delivery.

Radical radiotherapy with high-dose-rate brachytherapy for uterine cervix cancer long-term results.

The aim of this is to report the results of radical radiotherapy in carcinoma of the cervix treated by high-dose rate (HDR) intracavitary brachytherapy and external beam radiotherapy (XRT) at a single centre in Singapore. This is a retrospective analysis of 106 consecutive cases with histologically proven cervical cancer, treated by HDR brachytherapy and XRT at the Mount Elizabeth Hospital from 1990 to 1993. External beam radiotherapy to the pelvis was delivered with 6 MV photons, to 45-50.4 Gy in 1.8 Gy fractions. High-dose-rate brachytherapy comprised two to three applications of an intrauterine tandem with paired ovoids, to a median dose of 18 Gy to point 'A', carried out during XRT. All 106 patients completed treatment. Their ages ranged from 32 to 80 years (median 57 years). Most patients presented with stage II or III disease (44 and 37%, respectively) and with squamous cell carcinoma (91%). Median follow-up time was 59 months (range 2-169 months). The 5-year relapse-free survival rate across all stages was 71%. The corresponding overall survival rate was 69%. Local control was achieved in 86 patients (81%); six patients had residual disease (6%), and 14 patients had local recurrence (13%). Fourteen patients developed metastatic disease (13%). On univariate analysis, tumour stage, haemoglobin level, number of brachytherapy treatments and overall treatment time were found to be prognostic factors for overall survival. Late complications were mild (Radiation Therapy Oncology Group score 1-2), except for one patient with grade 4 rectal toxicity. The complication rates were 8, 14 and 45%, respectively, for the rectum, bladder and vagina (stenosis). The use of two to three fractions of HDR intracavitary brachytherapy in addition to pelvic XRT achieves good outcomes.

Emergence and kinetics of simian immunodeficiency virus-specific CD8(+) T cells in the intestines of macaques during primary infection.

In this report, three Mamu-A*01(+) rhesus macaques were examined to compare the emergence of simian immunodeficiency virus (SIV)-specific CD8(+) T cells in the intestines and blood in early SIV infection using a major histocompatibility complex class I tetramer complexed with the Gag(181-189) peptide. Fourteen days after intravenous inoculation with SIVmac251, large numbers of SIV Gag(181-189)-specific CD8(+) T cells were detected in the intestinal mucosa (3.1 to 11.5% of CD3(+) CD8(+) lymphocytes) as well as in the blood (3.1 to 13.4%) of all three macaques. By 21 days postinoculation, levels of tetramer-binding cells had dropped in both the intestines and blood. At day 63, however, levels of SIV Gag(181-189)-specific CD8(+) T cells in the intestines had rebounded in all three macaques to levels that were higher (8.6 to 18.7%) than those at day 21. In contrast, percentages of tetramer-binding cells in the peripheral blood remained comparatively stable (2.5 to 4.5%) at this time point. In summary, SIV Gag(181-189)-specific CD8(+) T cells appeared in both the intestinal mucosa and peripheral blood at a comparable rate and magnitude in primary SIV infection. Given that the intestine is a major site of early viral replication as well as the site where most of the total body lymphocyte pool resides, these data indicate that it is also an early and important site of development of antiviral immune responses.

Early immunologic events in mucosal and systemic lymphoid tissues after intrarectal inoculation with simian immunodeficiency virus.

The pathogenesis of human immunodeficiency virus transmission via the rectal route remains poorly understood. By use of the simian immunodeficiency virus (SIV)-rhesus macaque model and intrarectal inoculation with pathogenic SIVmac251, a significant increase was found in the percentage of CD11b(+) monocyte lineage cells expressing HLA-DR and/or B7-2 in local and peripheral immune inductive sites, but not in mucosal effector sites, as early as 7 days after inoculation and up to 50 days after inoculation. Moreover, at 21 and 50 days after inoculation, not only the gut but also the lung mucosa were depleted of CD4(+) T cells, which suggests that early loss of CD4(+) T cells may be a common feature of mucosal effector sites. These data suggest that, after intrarectal inoculation with SIV, early activation occurs within the monocyte lineage cell population at immunologic inductive sites, which is followed by a loss of CD4(+) T cells at local and distant mucosal effector sites.

Dynamics of CCR5 expression by CD4(+) T cells in lymphoid tissues during simian immunodeficiency virus infection.

Early viral replication and profound CD4(+) T-cell depletion occur preferentially in intestinal tissues of macaques infected with simian immunodeficiency virus (SIV). Here we show that a much higher percentage of CD4(+) T cells in the intestine express CCR5 compared with those found in the peripheral blood, spleen, or lymph nodes. In addition, the selectivity and extent of the CD4(+) T-cell loss in SIV infection may depend upon these cells coexpressing CCR5 and having a "memory" phenotype (CD45RA(-)). Following intravenous infection with SIVmac251, memory CD4(+) CCR5(+) T cells were selectively eliminated within 14 days in all major lymphoid tissues (intestine, spleen, and lymph nodes). However, the effect on CD4(+) T-cell numbers was most profound in the intestine, where cells of this phenotype predominate. The CD4(+) T cells that remain after 14 days of infection lacked CCR5 and/or were naive (CD45RA(+)). Furthermore, when animals in the terminal stages of SIV infection (with AIDS) were examined, virtually no CCR5-expressing CD4(+) T cells were found in lymphoid tissues, and all of the remaining CD4(+) T cells were naive and coexpressed CXCR4. These findings suggest that chemokine receptor usage determines which cells are targeted for SIV infection and elimination in vivo.

Identifying the target cell in primary simian immunodeficiency virus (SIV) infection: highly activated memory CD4(+) T cells are rapidly eliminated in early SIV infection in vivo.

It has recently been shown that rapid and profound CD4(+) T-cell depletion occurs almost exclusively within the intestinal tract of simian immunodeficiency virus (SIV)-infected macaques within days of infection. Here we demonstrate (by three- and four-color flow cytometry) that this depletion is specific to a definable subset of CD4(+) T cells, namely, those having both a highly and/or acutely activated (CD69(+) CD38(+) HLA-DR(+)) and memory (CD45RA(-) Leu8(-)) phenotype. Moreover, we demonstrate that this subset of helper T cells is found primarily within the intestinal lamina propria. Viral tropism for this particular cell type (which has been previously suggested by various studies in vitro) could explain why profound CD4(+) T-cell depletion occurs in the intestine and not in peripheral lymphoid tissues in early SIV infection. Furthermore, we demonstrate that an acute loss of this specific subset of activated memory CD4(+) T cells may also be detected in peripheral blood and lymph nodes in early SIV infection. However, since this particular cell type is present in such small numbers in circulation, its loss does not significantly affect total CD4(+) T cell counts. This finding suggests that SIV and, presumably, human immunodeficiency virus specifically infect, replicate in, and eliminate definable subsets of CD4(+) T cells in vivo.

Immunoregulatory changes in Kawasaki disease.

Kawasaki disease (KD) is an acute vasculitis of unknown etiology, occurring in young children and treated with intravenous gamma globulin (IVIG) to prevent significant cardiac morbidity and mortality. We studied KD patients pre- and post-IVIG therapy and at >40 days posttherapy, additionally comparing them with matched pediatric control patients and parents. Using three-color flow cytometry, we examined immune changes in KD, especially previously unassessed markers of T-lymphocyte activation, memory, and adhesion. The percentage of cells positive for CD19, CD25, CD38, and CD71 was significantly lower during convalescence compared with pre-IVIG (medians: CD19, 18% vs 26%, P = 0.0004; CD25, 6% vs 9% for CD3(+) cells, P = 0.0074; CD38, 78% vs 89% for CD8(+) cells, P = 0.0015; CD71, 1% vs 6% for CD4(+) cells, P = 0.0024). The proportion of CD3(+) cells increased (medians: CD3, 66% vs 45%, P < 0.0001). Values for all parameters varied greatly pre- and post-IVIG, but not in a consistent direction. The sole patient with cardiac abnormalities had the greatest pre-/post-IVIG variability. These changes support the involvement of T-lymphocytes in the acute KD vasculitic process. They also suggest that T-lymphocytes involved in endothelial damage during acute KD may be subsequently removed or eliminated from the peripheral blood.