Immune defense at the ocular surface

The ocular surface is constantly exposed to a wide array of microorganisms. The ability of the outer ocular system to recognize pathogens as foreign and eliminate them is critical to retain corneal transparency, hence preservation of sight. Therefore, a combination of mechanical, anatomical, and immunological defense mechanisms has evolved to protect the outer eye. These host defense mechanisms are classified as either a native, nonspecific defense or a specifically acquired immunological defense requiring previous exposure to an antigen and the development of specific immunity. Sight-threatening immunopathology with autologous cell damage also can take place after these reactions. This article discusses the innate and acquired corneal elements of the immune defense at the ocular surface. The relative roles of the various factors contributing to prevention of eye infection remain to be fully defined.     

Our experience in cardiac transplantation in Baskent University

Recently cardiac transplantation has an important place in treatment of end-stage cardiac failure. In Turkey between 2003 and 2005 at 10 centers 64 cardiac transplantations were performed including five at our facility. Herein we have presented our results. All patients were men of mean age 34.2 +/- 10.7 (17 to 44) years. Upon preoperative echocardiography their mean ejection fraction was 18% +/- 3.27% (17% to 23%). Pulmonary vascular resistance was 4.47 wood unit in one patient and in one case, there was Rh incompatibility between donor and recipient. We used HTK solution for protection of donor hearts. Mean ischemia time was 251.2 +/- 62.7 minutes (155 to 314). Mean aortic clamping time was 84 +/- 4.7 minutes (80 to 90). In all patients we performed a biatrial anastomosis technique. Hemofiltration was used to prevent hemodilution during operation. In the postoperative period four patients had acute renal dysfunction; one, a minor cerebrovascular accident; two, reoperated because of bleeding; one, cholestasis; one, temporary atrio-ventricular block; and one, mediastinitis. Mean follow-up time was 15.6 +/- 19.7 months (2 to 50). Neither early nor late mortality has occurred. All patients are in New York Heart Association class I. In all cases we used triple immunosuppressive therapy. In the follow-up period the mean number of cardiac biopsies per patient was 4.2 +/- 3.03 (2 to 8). Two cases had cardiac catheterization. As a complication of cardiac biopsy, pericardial tamponade developed in one patient; in another one we observed a right ventricular aneursym after cardiac biopsy. Cardiac transplantation was performed with low mortality and morbidity rates in end-stage cardiac failure patients with longer life expectancy and higher life quality. Unfortunately in our country, because of difficulties to find donor hearts, cardiac transplantations were small in number. For better results, we need a larger series.     

Regulation of metabolic responses by adipocyte/macrophage Fatty Acid-binding proteins in leptin-deficient mice

Fatty acid-binding proteins (FABPs) are cytosolic fatty acid chaperones that play a critical role in systemic regulation of lipid and glucose metabolism. In animals lacking the adipocyte/macrophage FABP isoforms aP2 and mal1, there is strong protection against diet-induced obesity, insulin resistance, type 2 diabetes, fatty liver disease, and hypercholesterolemic atherosclerosis. On high-fat diet, FABP-deficient mice also exhibit enhanced muscle AMP-activated kinase (AMPK) and reduced liver stearoyl-CoA desaturase-1 (SCD-1) activities. Here, we performed a cross between aP2(-/-), mal1(-/-), and leptin-deficient (ob/ob) mice to elucidate the role of leptin action on the metabolic phenotype of aP2-mal1 deficiency. The extent of obesity in the ob/ob-aP2-mal1(-/-) mice was comparable with ob/ob mice. However, despite severe obesity, ob/ob-aP2-mal1(-/-) mice remained euglycemic and demonstrated improved peripheral insulin sensitivity. There was also a striking protection from liver fatty infiltration in the ob/ob-aP2-mal1(-/-) mice with strong suppression of SCD-1 activity. On the other hand, the enhanced muscle AMPK activity in aP2-mal1(-/-) mice was lost in the ob/ob background. These results indicated that both decreased body weight and enhanced muscle AMPK activity in aP2-mal1(-/-) mice are potentially leptin dependent but improved systemic insulin sensitivity and protection from liver fatty infiltration are largely unrelated to leptin action and that insulin-sensitizing effects of FABP deficiency are, at least in part, independent of its effects on total-body adiposity.     

Pancreatic insufficiency in patients with chronic graft-versus-host disease

Diarrhea is a difficult diagnostic problem in patients with chronic graft-versus-host disease (cGVHD) because there are many causes of it. Although intestinal involvement has been reported in early studies of untreated cGVHD, this is now a very rare presentation of the disease. In addition to other etiologies, pancreatic insufficiency should also be considered in patients with cGVHD who demonstrate malabsorption. The pathogenesis of pancreatic insufficiency in these patients is unknown. Pancreatic enzyme supplements can be very effective in treating this rare condition.     

Immunomodulatory effects of extracorporeal photochemotherapy in patients with extensive chronic graft-versus-host disease

Extracorporeal photochemotherapy (ECP) has been associated with clinical improvement in several patients with acute and chronic graft-versus-host disease (cGVHD) after allogeneic bone marrow transplantation, but the mechanism of action is unknown. This study tested the hypothesis that in patients with cGVHD, ECP modulates alloreactivity by affecting activated lymphocyte populations or by altering the interaction between effector lymphocytes and antigen-presenting cells (APCs). Ten patients who had refractory cGVHD were treated with ECP, and the clinical response to and immunologic effects of this therapy were assessed. Seven patients had a response and 3 had no change in clinical manifestations of cGVHD. One patient died from catheter-related sepsis. Immunologic effects observed after ECP included normalization of inverted ratios of CD4 to CD8 cells, an increase in the number of CD3-CD56+ natural killer (NK) cells, and a decrease in CD80+ and CD123+ circulating dendritic cells. The results suggest that ECP modulates both NK cells and APC populations in patients with cGVHD.     

Intermediate-dose intravenous melphalan and blood stem cells mobilized with sequential GM+G-CSF or G-CSF alone to treat AL (amyloid light chain) amyloidosis

AL amyloidosis patients ineligible for dose-intensive melphalan (200 mg/m2) were enrolled on a phase 11 trial to be treated with two cycles of intermediate-dose melphalan (IDM 100 mg/m2) and mobilized blood stem cells (BSC). For mobilization patients were randomized to either GM-CSF 250 microg/m2 for 3 d followed by G-CSF 10 microg/ kg for 3 d (GM+G), or G-CSF 10 microg/kg for 6 d (G-alone), with leukaphereses on days 5, 6 and 7. To minimize morbidity, we planned to support each cycle with 3 5 x 106 CD34+ cells/kg and had a collection target of 7 x 10(6) CD34+ cells/kg. Those who did not achieve the target were treated with one cycle of IDM. 30 patients, a median of 62 years old and 7 months from diagnosis, were enrolled. Both mobilization regimens were generally well tolerated, and similar in terms of CD34+ cells and CFU-GM collected, but only 6/28 patients achieved the collection target (GM+G four, G-alone two). Despite a 19% incidence of grade 4 toxicities, IDM therapy was well tolerated. At a median follow-up of 24 months (19-36) 57% of patients had survived, 17% with durable complete haematological responses and 40% with improved or stable amyloid organ involvement, including 3/9 patients with predominant cardiac amyloid who are alive 2-3 years after treatment. The 100 d mortality was 20%. In conclusion, no definitive differences were identified between the mobilization regimens and IDM was an active regimen in AL for selected patients.     

Comparison of hospital costs for single-port and conventional laparoscopic colorectal resection: a case-matched study

Background

Whether single-port laparoscopic (SPL) colorectal resection is cost-effective in comparison to conventional laparoscopy remains unclear. The aim of this study is to compare hospital costs for single-port versus conventional laparoscopic colorectal resections.

Methods

Patients with available cost data who underwent (SPL) colorectal resection between December 2007 and December 2010 were matched with conventional (multiport) laparoscopic (CL) counterparts for age, gender, American Society of Anesthesiologists score, body mass index, operation type and year of surgery. Patients who underwent hand-assisted laparoscopic surgery were not included in the study. Direct hospital costs for the two groups were compared.

Results

There were 90 patients in the SPL group and 90 patients in the CL group. Age (p = 0.79), gender (p = 0.88), body mass index (p = 0.82), American Society of Anesthesiologists score (p = 1) and diagnosis (p = 0.85) were similar in both groups. Operation type (p = 1), estimated blood loss (p = 0.17) and length of hospital stay (p = 0.06) were comparable between the groups. Operation time was significantly shorter in the SPL group (p < 0.001), thus anesthesia cost was significantly lower in this group (p = 0.003). Total costs (p = 0.5), operating room (p = 0.65), nursing (p = 0.13), pharmacy (p = 0.6), radiology (p = 0.27), professional (p = 0.38) and pathology/laboratory (p = 0.46) costs were similar between the two groups.

Conclusions

Single-port laparoscopic colorectal resection can be performed with comparable hospital costs to conventional multiport laparoscopy.