A persistent tracheocutaneous fistula closed with two hinged skin flaps and rib cartilage interpositional grafting

Persistent tracheal fistula after tracheostomy decannulation is a recognized sequel to long-term tracheostomy use, causing important morbidity including difficult to vocalization and control of air secretions, recurrent pulmonary infections, and cosmetic and social problems. Herein, we reported a new method for closure of persistent tracheocutaneous fistula with rib cartilages. Compared to other techniques previously reported, the variations of our strategy were the use of temporary metal-covered tracheal stent and the hinged turnover skin bi-flaps reinforced with rib cartilage grafts. Rib cartilages were useful in order to reconstruct the trachea and prevent stenosis. Since it become difficult to obtain the maintenance of the trachea stability until healing of suture was well established, a covered metallic stent was also inserted to avoid flap collapse. The stent was removed 3 months later. Six months follow-up showed normal tracheal patency.     

Platelet function profiles in patients with type 2 diabetes and coronary artery disease on combined aspirin and clopidogrel treatment

To assess platelet function profiles in diabetic and nondiabetic patients on aspirin and clopidogrel therapy, two patient populations were included to investigate the 1) acute effects of a 300-mg clopidogrel loading dose (group 1, n = 52) and 2) long-term effects of clopidogrel (group 2, n = 120) on platelet function in diabetic compared with nondiabetic patients already on aspirin treatment. Patients were stratified according to the presence of type 2 diabetes. Platelet aggregation was assessed using light transmittance aggregometry (groups 1 and 2). Platelet activation (P-selectin expression and PAC-1 binding) was determined using whole-blood flow cytometry (group 2). Clopidogrel response was also assessed. In group 1, platelet aggregation was significantly increased in diabetic (n = 16) compared with nondiabetic (n = 36) patients at baseline and up to 24 h following a 300-mg loading dose (P = 0.005). In group 2, platelet aggregation and activation were increased in diabetic (n = 60) compared with nondiabetic (n = 60) subjects (P < 0.05 for all platelet function assays). Diabetic subjects had a higher number of clopidogrel nonresponders (P = 0.04). Diabetic patients have increased platelet reactivity compared with nondiabetic subjects on combined aspirin and clopidogrel treatment. Reduced sensitivity to antiplatelet drugs may contribute to the increased atherothombotic risk in diabetic patients.     

Influence of preservation solution on the isolation and culture of human hepatocytes from liver grafts

A major problem for the isolation and transplantation of hepatocytes is the lack of resources for obtaining viable hepatocytes. Improving this situation would enhance hepatic cell transplantation programs. Our objective was to evaluate the influence of the preservation solutions used during organ retrieval on the quality of hepatocytes isolated from liver tissue. We compared the results of the collagenase perfusion technique for isolation of hepatocytes in human livers flushed with University of Wisconsin (UW) and Celsior preservation solutions. Yield (number of viable cells per gram of tissue), cellular viability, efficiency of cells to attach to culture plates and form a monolayer, and drug metabolizing competence of the hepatocytes were measured. Successful isolation was achieved in 63% of the procedures using the UW solution and 100% of the procedures using the Celsior solution. In the UW group, significantly lower cell viability (38 +/- 41% vs. 79 +/- 14%, p < 0.05), yield of cells (4.0 +/- 5.2 x 10(6) vs. 8.2 +/- 5.6 x 10(6) cells/g, p < 0.05), and protein content at 24 h of culture (0.6 +/- 0.6 vs. 1.2 +/- 0.3 mg protein per plate, p < 0.05) than in Celsior solution were found. However, similar values of P450 activities were found in both groups. The more successful isolation, better yield, and higher cell viability obtained from human liver grafts preserved in Celsior solution, in comparison to UW solution, suggest Celsior solution as the most appropriate for preserving cadaveric hepatic tissue to be used for hepatocyte harvesting.     

Markers of inflammation before and after renal transplantation

BACKGROUND: This study aims to compare serum C-reactive protein (CRP), interleukin (IL-6), and tumor necrosis factor (TNF)-alpha in end-stage renal disease (ESRD) patients before versus after receiving renal transplantation (RT) and versus donors. METHODS: Serum samples from 37 ESRD patients (24 male, age 34+/-13 years) were collected before and after RT; in addition, samples from 31 donors were obtained at transplantation. CRP concentrations were measured using nephelometry, and TNF-alpha and IL-6 were measured by enzyme-linked immunoadsorbent assay. RESULTS: Ninety-two percent of recipients had a living donor, 73% received cyclosporine A, 27% tacrolimus, and 70% induction with daclizumab. Thirteen percent had acute rejection and 16% chronic allograft nephropathy. All inflammation markers decreased 6 months after RT, but only CRP was below baseline values (baseline: 5.0+/-3.5; 6 months: 3.0+/-0; 12 months: 3.2+/-0.7; 18 months: 3.2+/-0.6; donors: 3.6+/-1.5 mg/L; P<0.05), whereas median TNF-alpha (baseline: 0.1 [0.03-0.2]; 6 months: 0 [0-0.1]; 12 months: 0.3 [0.1-2.6]; 18 months: 0.6 [0.1-1.9]; donors: 0 [0-0.1] pg/mL; P<0.05) and IL-6 (baseline: 1.9 [1.2-7.1]; 6 months: 1.2 [0.6-28.3]; 12 months: 2.6 [1.3-3.4]; 18 months: 2.7 [1.7-4.2]; donors: 1.1 [0.6-1.9] pg/mL; P<0.05) significantly increased up to the end of follow-up. Before RT, CRP correlated with age (r 0.45, P=0.006) and albumin (r -0.36, P=0.04). TNF-alpha and IL-6 were correlated before (r 0.34, P=0.04) and after (r 0.55, P=0.02) RT. Inflammation markers were not different in patients who had acute rejection episodes or chronic nephropathy. CONCLUSIONS: Compared with controls, patients displayed an inflammatory phenomenon before receiving RT. Serum CRP decreased significantly after RT, whereas TNFalpha and IL-6 increased.     

Correlation of pupil size with visual acuity and contrast sensitivity after implantation of an apodized diffractive intraocular lens

PURPOSE: To determine whether pupil size is correlated with visual acuity and contrast sensitivity at all distances in eyes with an apodized diffractive intraocular lens (IOL). SETTING: Private Clinic, Oviedo, Spain. METHODS: Six months after surgery, the best corrected distance visual acuity, best distance-corrected near visual acuity, intermediate visual acuity, and distance contrast sensitivity under photopic (85 cd/m2) and mesopic (5 cd/m2) conditions were measured in 670 eyes of 335 consecutive patients who had implantation of the AcrySof ReSTOR Natural IOL (SN60D3, Alcon). Pupil diameters in distance vision were measured using a pupillometer. RESULTS: The logMAR best corrected distance acuity was significantly better with larger pupils (r = 0.297; P = 1.36 x 10(-8)), whereas logMAR best distance-corrected near acuity was significantly worse with larger pupils (r = 0.276, P = 1.02 x 10(-7)). For all pupil diameters, intermediate visual acuity worsened significantly as the distance of the test increased (P<.01). Statistically significant differences in photopic and mesopic contrast sensitivity at all spatial frequencies were found between the small-pupil and large-pupil groups (P<.01). Distance photopic contrast sensitivity and mesopic contrast sensitivity were better in patients with large pupils than in patients with small pupils. CONCLUSIONS: A larger pupil was correlated significantly with better distance visual acuity and with worse near visual acuity. For all pupil diameters, intermediate visual acuity worsened significantly as the distance of the test increased. Distance contrast sensitivity was better with larger pupils at all spatial frequencies in bright-light and dim-light conditions.     

HAART drugs induce mitochondrial damage and intercellular gaps and gp 120 causes apoptosis

HIV-1 infection is associated with serious cardiovascular complications, but the roles of HIV-1, viral proteins, and highly active antiretroviral therapy (HAART) drugs are not understood. HAART decreases the overall risk of heart disease but leads to metabolic disturbances and possibly coronary artery disease. We investigated toxicities of HIV-1, HIV-1 glycoprotein 120 (gp120), and HAART drugs for human coronary artery endothelial cells (CAECs), brain microvascular endothelial cells, and neonatal rat ventricular myocytes (NRVMs). HIV-1 and gp120, but not azidothymidine (AZT), induced apoptosis of NRVMs and CAECs. Ethylisothiourea, an inhibitor of nitric oxide synthase, inhibited apoptosis induction by gp120. AZT, HIV-1, and gp120 all damaged mitochondria of cardiomyocytes. HAART drugs, AZT, and indinavir, but not HIV-1, produced intercellular gaps between confluent endothelial cells and decreased transendothelial electrical resistance. In conclusion, HIV-1 and gp120 induce toxicity through induction of cardiomyocyte and endothelial cell apoptosis. HAART drugs disrupt endothelial cell junctions and mitochondria and could cause vascular damage.     

Therapy-related myelodysplastic syndrome

Introduction: Myelodysplastic syndrome (MDS) is a heterogeneous clonal disorder characterized by deregulation of apoptosis, dysplastic features in hematopoietic precursors, peripheral blood cytopenias and an increased risk for transformation to acute leukemia. Roughly 20% of MDS are therapy related (t-MDS), and this is considered an independent adverse prognostic factor.

Areas covered: This review based on a comprehensive literature search provides an overview on the main features of t-MDS, including its epidemiology, risk factors, molecular pathogenesis, prognostic classifications and therapy.

Expert opinion: Increasing evidence points out that the most important event in t-MDS is genetic alterations in hematopoietic stem precursor cells, however, ineffective hematopoiesis may also result from abnormalities in the bone marrow microenvironment. Thus, novel views onto the processes of t-MDS are needed such as the osteohematology concept. On the other hand, the number of people living with and beyond cancer is increasing worldwide; thus, most emphasis should be placed on preventing secondary malignancies such as t-MDS. From this review, it becomes clear that we are in urgent need not only to deepen our understanding of the leukemogenesis mechanisms induced by exposure to chemotherapy and radiation but also to translate this knowledge into clinical strategies aimed at risk reduction.     

Squamous-cell carcinoma developing within anal lichen planus

AIM: We present a case of squamous-cell carcinoma developing within perianal lichen planus. This is a chronic or recurrent cutaneous and/or mucosal dermatosis affecting less than 1 percent of the population. Neoplastic degeneration of cutaneous lichen planus is rare; only one case of squamous-cell carcinoma developing within perianal lichen planus has been described up until now in the international literature. CASE REPORT: Our case involved a 68-year-old woman with chronic, long-term lichen planus spreading all over the vulva and perianal region and the mucosa of the anal canal, where squamous-cell carcinoma developed within the perianal lichen planus. Treatment consisted of wide, circular excision of the perianal skin and mucosectomy of the anal canal up to as far as 1 cm above the dentate line. Reconstruction was performed by means of two V-Y bilateral subcutaneous flaps. CONCLUSION: Wide excision was performed not only to remove the squamous-cell carcinoma but also the lichen planus to prevent recurrence of metachronous or synchronous squamous-cell carcinoma. Follow-up at one year after surgery showed no local recurrence of either lichen planus or squamous-cell carcinoma, which suggests that surgical removal should be the therapy of choice for long-term, chronic perianal lichen planus that has proved to be resistant to medical therapy.