Stercoral perforation requiring subtotal colectomy in a patient on methadone maintenance therapy.

Stercoral perforation of the colon is a rare but serious complication of chronic constipation. We present a case of stercoral perforation requiring subtotal colectomy in a 41-year-old female who had been on methadone maintenance for a history of long-term intravenous heroin use. Our case highlights the importance of prompt and thorough surgical intervention in the successful treatment of this rare condition.

Role of 3beta-hydroxysteroid-delta 24 reductase in mediating antiinflammatory effects of high-density lipoproteins in endothelial cells.

OBJECTIVE: The purpose of this study was to investigate the ability of high-density lipoproteins (HDLs) to upregulate genes with the potential to protect against inflammation in endothelial cells. METHODS AND RESULTS: Human coronary artery endothelial cells (HCAECs) were exposed to reconstituted HDLs (rHDLs) for 16 hours before being activated with tumor necrosis factor-alpha (TNF-alpha) for 5 hours. rHDLs decreased vascular cell adhesion molecule-1 (VCAM-1) promoter activity by 75% (P<0.05), via the nuclear factor-kappa B (NF-kappaB) binding site. rHDLs suppressed the canonical NF-kappaB pathway and decreased many NF-kappaB target genes. Suppression of NF-kappaB and VCAM-1 expression by rHDLs or native HDLs was dependent on an increase in 3beta-hydroxysteroid-Delta 24 reductase (DHCR24) levels (P<0.05). The effect of HDLs on DHCR24 is dependent on SR-BI but not ABCAI or ABCGI. Silencing DHCR24 expression increased NF-kappaB (1.2-fold, P<0.05), VCAM-1 (30-fold, P<0.05), and NF-kappaB p50 (4-fold, P<0.05) and p65 subunits (150-fold, P<0.05). TNF-alpha activation of siDHCR24-treated cells increased expression of VCAM-1 (550-fold, P<0.001) and NF-kappaB (9-fold, P<0.001) that could no longer be suppressed by rHDLs. CONCLUSIONS: Results suggest that antiinflammatory effects of rHDLs are mediated partly through an upregulation of DHCR24. These findings raise the possibility of considering DHCR24 as a target for therapeutic modulation.

Advanced glycation end products decrease mesangial cell MMP-7: a role in matrix accumulation in diabetic nephropathy?

Increased extracellular matrix material is a pathological hallmark of diabetic nephropathy. In addition to collagens, a variety of non-collagenous glycoproteins such as fibronectin also accumulate in the kidney of diabetics. The effect of diabetes on degradative pathways, in particular those involving non-collagenous proteins, are relatively unexplored. In this study, we determined the expression of the major matrix metalloproteinase (MMP) responsible for degrading the non-collagenous matrix glycoprotein fibronectin. Furthermore, the modulation of these MMPs by advanced glycation end products (AGE), a key factor in the diabetic milieu, was explored. Exposure of mesangial cells to AGEs led to a significant reduction in MMP-7, but not MMP-3 or -10. MMP-7 expression was normalized by both aminoguanidine, an inhibitor of glycation product formation, or by a neutralizing anti-transforming growth factor-beta (TGF-beta) antibody. In streptozotocin-induced diabetic rats, the diminution in MMP-7 expression and excessive fibronectin accumulation were attenuated by aminoguanidine. Humans with type 2 diabetes and nephropathy displayed similar alterations in MMP-7 to their rodent counterparts. Our findings suggest that diminished expression of the glycoprotein-degrading enzyme, MMP-7, may play a role in fibronectin accumulation in the diabetic kidney in response to AGEs and/or TGF-beta.

Simple technique for proper approximation and closure of peritoneal and rectus sheath defects at port site after laparoscopic surgery.

Complex intra-abdominal surgical procedures can now be performed with laparoscopy, and laparoscopic cholecystectomy has become the gold standard in the care of patients with cholelithiasis. This and other surgically challenging procedures involve use of multiple large (10-mm-15-mm) ports. A standard laparoscopic cholecystectomy employs two 10-mm trocar incisions. Development of incisional hernia from these port sites is well recognized unless the rectus sheath is closed properly. This makes proper closure of the incisions for larger ports critical, especially 10-mm to 15-mm ports. However, securing abdominal wall bleeding and closing facial defects through a small incision can be a cumbersome task. We have developed a simple technique using the regular curved needle and sutures for closure of rectus sheath defects through a small port-site incision.

Carbon dioxide volume and intra-abdominal pressure determination before the creation of a pneumoperitoneum.

Laparoscopic surgery generally is regarded as a safe procedure when a preset pressure is used in the carbon dioxide insufflator. However, a fixed pressure setting is not appropriate when insufflating a very large or a very small abdomen. Presently, extrapolation from the commonly used 15 mm Hg to an appropriate and safe pressure cannot be easily determined except by a crude trial and error method. We developed an anthropometric formula to calculate the total abdominal cavity capacity and the corresponding pressure necessary to obtain safe pneumoperitoneum. This anthropometric formula calculates the total abdominal capacity by measuring one diameter from the symphysis pubis to the xyphoid bone, a second diameter as half the initial measurement, and a third diameter by dividing the waist measurement (minus an estimated percentage of body fat) and dividing that product by pi. The product of the three diameters is then multiplied by a constant (K = 0.5). We studied prospectively 20 patients whose indications for laparoscopic surgery necessitated creation of a pneumoperitoneum. The patients were divided into two groups: group A (n = 10), patients who were observed with the intra-abdominal pressure fixed at 15 mm Hg while recording the amount of distension produced in the abdominal cavity during creation of the pneumoperitoneum; and group B (n = 10) in whom pneumoperitoneum was obtained based on the initial volume of carbon dioxide-insufflation previously calculated using our formula. Based on our observations, we conclude that this anthropometric formula can be used successfully in predicting a safe level of insufflation in relation to the patient's size.