A-FABP and Oxidative Stress Underlie the Impairment of Endothelium-Dependent Relaxations to Serotonin and the Intima-Medial Thickening in the Porcine Coronary Artery with Regenerated Endothelium

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Prospective Study on Lamivudine-Resistant Hepatitis B in Renal Allograft Recipients

The natural history of lamivudine-resistant hepatitis B virus (HBV) infection in renal transplant recipients (RTx) is unclear, despite its increasing incidence. Twenty-nine HBsAg-positive RTx with rising HBV DNA received lamivudine therapy. The course of lamivudine-resistant HBV infection was studied prospectively. During 68.7 +/- 12.5 months of follow-up, 14 (48.3%) patients developed lamivudine resistance, at 10-35 months (mean 16.9 +/- 7.0). All showed mutant sequences at codons 552 and 528 of the YMDD motif, while 13 patients demonstrated wild-type sequence at codon 555. Lamivudine resistance was unrelated to patient demographics, HBeAg status/sero-conversion, or genotype. Following resistance, HBV DNA and alanine aminotransferase showed an initial increase followed by spontaneous gradual reduction. The subsequent peak HBV DNA was lower (1.26 +/- 1.09 x 10(9) vs. 6.26 +/- 12.23 x 10(9) copies/mL, p = 0.011), while that of alanine aminotransferase was higher (196 +/- 117 vs. 77 +/- 47 imicro/l, p = 0.005), compared with pretreatment levels. Post-resistance hepatitic flare occurred in 11 (78.6%) patients. This was transient in four (36.4%), but became chronic in six (54.5%) patients. Decompensation was noted in one patient during this flare, but all survived. We conclude that drug resistance is prevalent in lamivudine-treated RTx. Despite a lower ensuing peak viremia compared with baseline, hepatitic flare is common. While most patients have spontaneous resolution, a minority may develop potentially fatal decompensation during the preceding exacerbation.     

CD4-T-cell antigen receptor complexes on human leukemia T cells.

CD4 and T-cell antigen receptor (TCR) comodulate from the surface of human and murine T cells following exposure to monoclonal anti-CD4 or anti-TCR. This comodulation may occur because expression of CD4 and TCR is regulated by similar transmembrane signals or because CD4 and TCR are physically associated. To study multimolecular assemblies on the plasma membrane, we developed a flow cytometric method for detecting singlet-singlet energy transfer between fluorescein isothiocyanate (FITC)- and tetramethylrhodamine isothiocyanate (TRITC)-conjugated monoclonal antibodies as sensitized TRITC emission on intact, single cells. Using this procedure, we detected CD4-TCR complexes on the surface of the transformed human leukemia T cells, HPB-ALL, in the absence of stimulation. More than one CD4 were found in association with one TCR. CD4-TCR complexes were not in rapid equilibrium with free CD4 and free TCR, and they were not induced by the dye-labeled anti-CD4 or anti-TCR.     

Oxygen radical-mediated injury of myocytes-protection by propranolol

UIe effects of propranolol and atenolol on free radical mediated injury in myocytes were examined. Freshly isolated adult canine myocytes were incubated with a superoxide generating (from dihydroxyfumarate) and Fe-catalyzed free radical system. Exposure of the myocytes to free radicals for 20 min resulted in more than a 5-fold increase in thiobarbituric acid reactant (peroxide) formation and elevated levels of lactate dehydrogenase (LDH) activity released into the media compared to controls. Ultrastructurally, severe sarcolemmal damage, mitochondrial and myofibril derangements were evident. At 40 min, cellular viability (trypan blue exclusion) in the samples exposed to free radicals decreased to about one-third of controls; concomitantly, major losses in total cellular phospholipids occurred. When the cells were pretreated with 200 microM propranolol before the addition of free radicals, both peroxide formation and increased LDH release were inhibited; in agreement, complete ultrastructural preservation was observed. In addition, the subsequent losses in cellular viability and phospholipids were prevented. For comparison, the more water soluble beta-blocker, atenolol at 200 microM was shown ineffective in providing significant protection against the induced injury. The results suggest that propranolol may provide antiperoxidative protection to myocytes when elevated levels of free radicals are present.     

First trimester combined screening for Trisomy 21 in Hong Kong: outcome of the first 10,000 cases

Objective.?To examine the effectiveness of first trimester fetal Trisomy 21 (T21) screening using a combination of maternal age, nuchal translucency, maternal serum levels of free β-hCG and PAPP-A in a predominantly Chinese population in Hong Kong.

Methods.?Consecutive women who underwent the combined screening for T21 between 11 and 13 + 6 weeks of gestation between 2003 and 2007 were recruited. Risk of T21 was calculated using Fetal Medicine Foundation algorithm and karyotyping was advised when the risk was 1:300 or above. All women were followed up for pregnancy and fetal outcome.

Results.?10,363 fetuses underwent screening. 99% of the women were Chinese and 27.4% were at or above 35 years old. 618 fetuses were screened positive (5.9%), which included 31 cases of T21, 14 cases of T18, 7 cases of T13, 10 cases of 45XO and 7 cases of other chromosomal abnormalities. Among the 9745 screened negative fetuses all but 50 (0.5%) had a known outcome, which included three T21 and four other chromosomal abnormalities. All were subsequently identified at the morphology scan except for one case of T21. The detection rate and false positive rates for T21 were 91.2% and 5.4%, respectively and the positive predictive value for all chromosomal abnormalities was 1 in 9.

Conclusions.?Combined screening for T21 is highly effective among Chinese women. Training, quality control, regular auditing and follow up are essential to maintain screening standards.     

Sirolimus is associated with reduced islet engraftment and impaired beta-cell function

Successful islet transplantation depends on the infusion of sufficiently large quantities of islets, but only a fraction of transplanted islets can survive and become engrafted, and yet the underlying mechanism remains unclear. In this study, we examined the effect of sirolimus, a key component of the immunosuppressive regimen in clinical islet transplantation, on islet engraftment and function. To distinguish the effect of sirolimus on immune rejection from its effect on islet engraftment, we used a syngeneic model. Diabetic mice were transplanted with 250 islets under the renal capsule, followed by treatment with sirolimus or vehicle for 14 days. Thirty days posttransplantation, islet grafts were retrieved for the determination of insulin content and vascular density. Compared with mock-treated controls, diabetic recipient mice receiving sirolimus exhibited impaired blood glucose profiles and reduced glucose-stimulated insulin secretion, correlating with reduced intragraft insulin content and decreased vascular density. Islets exposed to sirolimus for 24 h in culture displayed significantly diminished glucose-stimulated insulin release, coinciding with decreased pancreas duodenum homeobox-1 and GLUT2 expression in cultured islets. Furthermore, sirolimus-treated diabetic recipient mice, as opposed to mock-treated controls, were associated with dyslipidemia. These data suggest that sirolimus, administered in the early posttransplantation phase, is a confounding factor for reduced islet engraftment and impaired beta-cell function in transplants.     

Anatomic approximation approach to correction of transverse facial clefts

Transverse clefts of the oral cavity have significant impacts on both appearance and function. Many methods of repair have been described, but there is no consensus on optimal approach. In addition, dissatisfaction with scars, distortion of appearance, and recurrent deformity have led to complex surgical designs that are difficult to understand and reproduce. We describe a simple approach to repair that is based upon anatomic approximation of lip components and accurate repair of the muscle.Twenty patients underwent repair by the senior author, who devised the approach, and the corresponding author, who adopted it. Eight (62%) patients had right-sided clefts, three (23%) patients had left-sided clefts, and two (15%) patients had bilateral clefts. One patient had an associated branchial cleft remnant, two patients had multiple branchial cleft remnants and tragus deformities, one patient had craniofacial microsomia with microtia, and one patient had a contralateral Tessier 1 cleft. Mean age of the patients at repair was 23 months. All patients achieved normal oral competence, have favorable scars and commissure appearance, and have had no recurrent deformity. None of the patients have required revision.The described surgical approach is reproducible, easy to understand, and can produce favorable outcomes.     

Pelvic floor ultrasound in the diagnosis of sling complications

Purpose

The mid-urethral synthetic sling (MUS) procedure has become the standard of care for treatment of female stress urinary incontinence. However, a small number of patients will have complications following MUS including failure, obstructive voiding, sling erosion, or chronic pain. This paper discusses the role of 2D and 3D ultrasound imaging in the evaluation of the female patient with complications following placement of a synthetic mid-urethral sling.

Results

The MUS is easily visualized as an echogenic structure on ultrasound and can be imaged by transperineal, transvaginal and introital approaches. Ultrasound allows dynamic assessment of the sling and can assist in the diagnosis of sling failure, obstruction, erosion and mesh related pain.

Conclusions

Pelvic floor ultrasound has an emerging role in the assessment of complications following MUS surgery. 3D ultrasound can assist the clinician in assessment of the complex patient with multiple slings or meshes in situ.