Effect of Glucagon-like Peptide-2 (GLP-2) on Diurnal SGLT1 Expression

Glucagon-like peptide 2 (GLP-2) is a 33-amino acid gut peptide that leads to villus hyperplasia and altered gene expression. We examined the effect of chronically administered GLP-2 on diurnal gene expression rhythms using the Na+/glucose cotransporter 1 (SGLT1) as the index. Animals were treated with [Gly2]GLP-2 (twice daily; 1microg/g body weight) or vehicle (control) for 10 days. Rats were killed at either 3 hr or 9 hr after light onset (ZT3 and ZT9, respectively), an interval during which SGLT1 expression exhibits a robust induction. SGLT1 mRNA expression was assessed by Northern blotting and in situ hybridization. SGLT1 protein was examined by immunofluorescence and Western blotting. Tissues from GLP-2-treated rats had increased villus height, crypt depth, and proliferation index (P < 0.05). GLP-2 administration did not alter the diurnal increase in mRNA levels of SGLT1, GLUT2, or GLUT5. However, in GLP-2-treated rats, the SGLT1 protein amount increased at both ZT3 and ZT9. Moreover, SGLT1 was preferentially localized to the apical membranes in this group. GLP-2 does not adversely affect the diurnal expression rhythm of SGLT1 and appears to increase membrane expression of the protein. These biological actions of GLP-2 may contribute to its therapeutic value in intestinal diseases.     

The effect of cardiac genetic testing on psychological well-being and illness perceptions

Objective

To assess the effects of positive cardiac genetic diagnoses, ICD discharges, and arrhythmias on measures of psychological well-being.

Methods

Fifty-eight adults with prior cardiac genetic testing were enrolled. Patient well-being was determined using the SF-36 (QoL), HADS-A and HADS-D (anxiety/depression), and IPQ-R (patients' perceptions of illness). Patients with positive and negative cardiac genetic test results were compared using non-parametric statistics.

Results

Genetic testing yielded 76% with a positive diagnosis and 29% reported an ICD shock. QoL assessments (n = 33) were within normal ranges (mean of 50) with the exceptions of general health (44.1 ± 12.2, p < 0.01) and bodily pain (55.1 ± 9.1, p < 0.01) domains, but only the bodily pain domain showed differences between those with positive and negative cardiac genetic test results. Subjects with ICD discharges had higher scores than those without shocks in consequential and emotional IPQR subscales as well as greater perceived risks of experiencing a serious cardiac event, developing additional symptoms, or limitations in daily activities.

Conclusion

Positive genetic results did not negatively impact patient well-being with the exception of the bodily pain domain of the SF-36.     

创伤及休克肠道细菌移位的研究

研究大面积皮肤撕脱伤和失血性休克情况下，肠道细菌移位的发生率，设计了兔的试验模型。实验组30只兔，腹部皮肤撕脱100×90mm,并行股动脉放血成休克模型。对照组10只兔，仅放血致休克。结果：对照组术后5h取标本未发现肠道细菌移位；实验组术后lh采标本已有肠道细菌移位，3h、5h组肠道细菌移位达30％。讨论了创伤及休克肠道细菌移位的临床价值。     

The safety and efficacy of OP-1 (rhBMP-7) as a replacement for iliac crest autograft for posterolateral lumbar arthrodesis: minimum 4-year follow-up of a pilot study.

BACKGROUND CONTEXT: Although autogenous bone is still considered to be the gold standard graft material for promoting spinal fusion, other bone graft substitutes have been developed in an attempt to improve arthrodesis rates and avoid the complications associated with the procurement of autograft. The bone morphogenetic proteins (BMPs) represent a family of osteoinductive growth factors that are known to stimulate the osteoblastic differentiation of stem cells. Osteogenic protein-1 (OP-1) Putty is a commercially available BMP preparation that is already approved for use in humans. Previous clinical studies involving patients with degenerative spondylolisthesis have reported that the efficacy and safety of OP-1 Putty is comparable to that of autograft at both 1- and 2-year follow-up. PURPOSE: The purpose of this study was to evaluate the intermediate-term efficacy and safety of OP-1 Putty as an alternative to autogenous bone by comparing the 4-year radiographic, clinical, and safety data of these same patients who underwent decompression and uninstrumented fusion with either OP-1 Putty or iliac crest autograft. STUDY DESIGN/SETTING: A prospective, randomized, controlled, multicenter clinical pilot study. PATIENT SAMPLE: Thirty-six patients undergoing decompressive laminectomy and single-level uninstrumented fusion for degenerative spondylolisthesis and symptomatic spinal stenosis were randomized in a 2:1 fashion to receive either OP-1 Putty (24 patients) or autogenous iliac crest bone graft (12 patients). OUTCOME MEASURES: Patient-reported outcome measures consisting of Oswestry Disability Index and Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) scores were used to evaluate clinical efficacy. Perioperative data including operative time, estimated blood loss, and duration of hospital stay were also recorded for each surgery. Postoperatively, a neurological examination and an assessment of donor-site pain (if applicable) were performed at every follow-up visit. Radiographic fusion success was defined as the presence of continuous bridging bone formation between the transverse processes at the level of the spondylolisthesis with minimal motion evident on dynamic lateral x-ray films. The primary efficacy endpoint was the overall success rate, a composite measure derived from both radiographic and clinical parameters. The safety of OP-1 Putty was confirmed by comparing the nature and frequency of all adverse events and complications that were prospectively observed in either of the groups. METHODS: Thirty-six patients with degenerative spondylolisthesis and symptoms of neurogenic claudication underwent decompressive laminectomy and single-level uninstrumented fusion with either OP-1 Putty or autograft. All patients were evaluated at 6 weeks and 3, 6, 9, 12, and 24 months, after which time they were instructed to return on a yearly basis. Multiple neuroradiologists blinded to the assigned treatment reviewed static and dynamic X-ray films with digital calipers to assess fusion status according to the presence of continuous bridging bone across the transverse processes as well as the amount of residual motion evident at the level of interest. Oswestry Disability Index surveys and SF-36 questionnaires were used to assess clinical outcomes. RESULTS: At the 48-month time point, complete radiographic and clinical data were available for 22 of 36 patients (16 OP-1 Putty and 6 autograft) and 25 of 36 patients (18 OP-1 Putty and 7 autograft), respectively. Radiographic evidence of a solid arthrodesis was present in 11 of 16 OP-1 Putty patients (68.8%) and 3 of 6 autograft patients (50%). Clinically successful outcomes defined as at least a 20% improvement in preoperative Oswestry scores were experienced by 14 of 19 OP-1 Putty patients (73.7%) and 4 of 7 autograft patients (57.1%); these clinical findings were corroborated by similar increases in SF-36 scores. The respective overall success rates of the OP-1 Putty and autograft group were 62.5% and 33.3%. In this study, there were no incidents of local or systemic toxicity, ectopic bone production, or other adverse events directly related to the use of OP-1 Putty. CONCLUSION: Despite the challenges associated with obtaining a solid uninstrumented fusion in patients with degenerative spondylolisthesis, the rates of radiographic fusion, clinical improvement, and overall success associated with the use of OP-1 Putty were at least comparable to that of the autograft controls for at least 48 months after surgery. These results appear to validate the short-term results previously reported for OP-1 Putty and suggest that this material may potentially represent a viable bone graft substitute for certain fusion applications.     

Added value of diffusion‐weighted imaging in the MRI assessment of perilesional tumor recurrence after chemoembolization of hepatocellular carcinomas

Purpose

To investigate the additional value of diffusion‐weighted imaging (DWI) in the MRI assessment of perilesionally recurrent hepatocellular carcinomas (HCCs) after transcatheter arterial chemoembolization (TACE).

Materials and Methods

For gadopentetate dimeglumine‐enhanced multiphasic dynamic images with precontrast T1‐ and T2‐weighted images of 23 patients treated with TACE, two radiologists independently sorted the confidence levels for the presence of a viable tumor in the vicinity of the treated lesions into five grades. In another session, images from DWI (b factor = 50, 400, and 800 s/mm²) were added to the previously reviewed images and the same radiologists sorted the confidence levels.

Results

A total of 26 lesions (0.7–3.5 cm) from 16 patients were confirmed to be perilesional recurrences of HCC. The area under the receiver operating characteristic curve (A_z) for the second interpretation session (0.826) was not significantly different (P = 0.299) from that of the first session (0.859). The overall sensitivity was increased from 85% to 92%, but the specificity decreased from 65% to 50% after adding DWI.

Conclusion

The addition of DWI has the potential to improve sensitivity, but not the overall diagnostic accuracy, in the assessment of perilesional recurrence of HCCs after chemoembolization. J. Magn. Reson. Imaging 2009;30:153–160. © 2009 Wiley‐Liss, Inc.     

Accuracy of gadoxetic acid-enhanced magnetic resonance imaging for the diagnosis of sinusoidal obstruction syndrome in patients with chemotherapy-treated colorectal liver metastases

Objective  

To assess whether reticular hypointensity on hepatobiliary phase images of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) is a diagnostic finding of sinusoidal obstruction syndrome (SOS) in patients with hepatic metastases who have undergone chemotherapy.     

Transvaginal cholecystectomy without laparoscopic support using prototype flexible endoscopic instruments in a porcine model

Background

Transvaginal cholecystectomy with laparoscopic assistance has been performed safely in humans. The next goal was to develop a natural orifice transluminal endoscopic surgery (NOTES) technique to perform cholecystectomy without laparoscopic instruments using one flexible endoscope and flexible accessories. The aim of the study was to test the feasibility of the procedure in a survival porcine model.

Methods

Cholecystectomies were attempted in five 88–130-lb. pigs with a planned 2-week survival. Prototype flexible instruments (NOTES Toolbox, Ethicon Endo-Surgery, Inc.) were used to aid in access, dissection, and removal of the gallbladder via the transvaginal route.

Results

Cholecystectomy could be completed without abdominal incision using prototype instruments in four out of five pigs. The cystic duct could be exposed with a flexible hook knife and clips applied. The steerable trocar improved stability and the precision of the dissection. The critical view was established in all five pigs. Dissection of the gallbladder off the liver bed was imprecise resulting in gallbladder perforation in all pigs and liver hemorrhage in two. At necropsy, all clips on the cystic duct were secure and no bile leak, bowel injury, or adhesions were present.

Conclusions

NOTES cholecystectomy without laparoscopic support is feasible but challenging using prototype flexible endoscopic devices. A prototype clip applier was effective in controlling the cystic duct. Further improvements in instrument design to ensure precision and safety are needed before flexible devices should be used for pure NOTES procedures in humans.     

A case of mesenteric cystic lymphangioma: fat saturation and chemical shift MR imaging

Mesenteric cystic lymphangioma is an uncommon lesion that may be difficult to diagnose radiologically. In our case, a septate cystic mass showed fluid attenuation on a computed tomography scan. We were able to define the fat content within the cystic tumor by magnetic resonance (MR) imaging. The presence of fat within an intra-abdominal cystic mass is suggestive of a dermoid cyst, cystic lymphangioma, or lymphocele. The pathologic diagnosis revealed a cystic lymphangioma, which originated from the mesentery. Although the MR imaging features of dermoid cysts and lymphangiomas are well known, the demonstration of fat content by chemical shift and fat saturation MRI has not yet been reported for a cystic lymphangioma.