Pre-treatment quality of life as a predictor of distant metastasis-free survival and overall survival in patients with head and neck cancer who underwent free flap reconstruction.

PURPOSE: This study examined the prognostic associations of pre-treatment quality of life (QoL) with overall survival (OS) and distant metastasis-free survival (DFMS) among patients with head and neck cancer (HNC) who underwent free flap reconstruction. METHODS: A cohort of 127 HNC patients who received free flap reconstruction between November 2010 and June 2014 at a hospital were recruited. Pre-treatment QoL was measured by the University of Washington Quality of Life Questionnaire, which contains six physical domains, including speech, swallowing, appearance, saliva, taste and chewing, as well as the six social-emotional domains of pain, activity, recreation, shoulder, mood, and anxiety. Cox regression analyses were performed. RESULTS: Results showed that pre-treatment QoL was predictive of OS and DMFS. Of the domains, swallowing, chewing, speech, taste, saliva, pain and shoulder were demonstrated to be significant predictors of OS. Additionally, swallowing, chewing, speech, pain and activity were demonstrated making significant contributions to DMFS. CONCLUSION: Our data supported that physical domains of pre-treatment QoL were predictors for OS and DFMS in HNC patients with free-flap reconstruction. Longitudinal studies are warranted to clarify the prognostic abilities of social-emotional domains. Information on pre-treatment QoL should be taken into account to individualize care plan for these patients, and hence prolong their survival.

The in vitro protection of human decay accelerating factor and hDAF/heme oxygenase-1 transgenes in porcine aortic endothelial cells against sera of Formosan macaques.

To mitigate hyperacute rejection, pigs have been generated with alpha-Gal transferase gene knockout and transgenic expression of human decay accelerating factor (hDAF), MCP, and CD59. Additionally, heme-oxygenase-1 (HO-1) has been suggested to defend endothelial cells. Sera (MS) (0%, 1%, 5%, 10%, and 15%) from Formosan macaques (Macaca cyclopis, MC), an Old World monkey wildly populated in Taiwan, was used to test the protective in vitro, effects of hDAF or hDAF/hHO-1 on porcine aortic endothelial cells (pAEC) derived from hDAF(+), hDAF(+)/hHO-1(+), and hDAF(+)/hHO-1(-) and 1 nontransgenic pAEC. Ten percent human serum (HS) served as a positive control. When MS addition increased to 10% or 15%, all transgenic pAEC exhibited a greater survival than nontransgenic pAEC. Noticeably, 15% MS reduced survived to <10% versus >40% in nontransgenic and transgenic pAEC, respectively. These results revealed that hDAF exerted protective effects against MC complement activation. However, comparing with 10% MS and HS in pAEC of nontransgenic pigs, the survivability was higher in HS, suggesting that complement activation by MS was more toxic than that by HS. Furthermore, hDAF(+)/hHO-1(+) showed no further protection against effects of MS on transgenic pAEC.

Urachal adenocarcinoma following kidney transplantation: the first case report.

A 53-year-old man who underwent successful kidney transplantation for stage 5 chronic kidney disease presented to our clinic with intermittent painless gross hematuria. Urachal adenocarcinoma, stage III A by Sheldon system, was diagnosed after serial histopathologic and radiological studies. The patient was treated with extended partial cystectomy, en bloc resection of urachus and umbilicus, pelvic lymphadenectomy, and ileocystoplasty. There were no complications seen in this patient. Neither urachal adenocarcinoma recurrence, metastasis, nor de novo uroileal cancer developed during 48-month follow-up. His reconstructed bladder functioned efficiently, without compromising the transplanted kidney function. Our case demonstrated that conservative surgery and augmentation ileocystoplasty could be offered to kidney transplant recipients with localized urachal carcinoma.

Optimal C2 concentration of cyclosporin corrected with good efficacy and safety in Asian kidney transplant recipients.

INTRODUCTION: Calcineurin inhibitors (CNI) are known for their renal toxicity. Lower CNI exposure is a reasonable option to mitigate potential CNI-induced renal toxicity. Herein we have presented our long-term results after lower cyclosporine (CsA) exposure in the first year. MATERIALS AND METHODS: Between 1997 and 2004, 63 renal transplant recipients received CsA-based immunosuppression. CsA dosing was adjusted according to the 2-hour whole blood concentration (C2) level. We retrospectively reviewed acute rejection and graft survivals rates, as well as whole blood C2 levels. RESULTS: Review of serial mean C2 concentrations at 1, 2, 3, 6, and 12 months after transplantation were 1341, 1241, 1191, 1059, and 927 ng/mL, respectively. These levels were slightly lower than those suggested by the Consensus for C2 levels by Levy et al in 2002, namely, 1600 to 2000 ng/mL (mean, 1700); 1400 to 1600 ng/mL (mean, 1500); 1200 to 1400 ng/mL (mean, 1300); 1000 to 1200 ng/mL (mean, 1100), and 800 to 1000 ng/mL (mean, 900), respectively. Acute rejection rate at 3 months and 1 year are 17.5% and 23.8%. Graft survival at 1 year was 97% and at 5 years, 89%. Two patient were lost to fulminant hepatitis and acute myocardial infarction during the first year, which were not associated with underimmunosuppression. CONCLUSION: Appropriate CsA C2 levels may be lower among Taiwanese. Our C2 dosing strategy resulted in good outcomes with acceptable side effects in our single-center experience. Appropriate CsA C2 levels for Asians deserve more attention in trials of larger scale; most reference levels are presently concluded from studies of Caucasians.

Sirolimus does not absolutely abolish the occurrence/recurrence of urothelial carcinoma in renal transplant recipients.

OBJECTIVE: Sirolimus (SRL), an immunosuppressant shown to possess anti-proliferative properties, was hypothesized to mitigate the occurrence of posttransplantation malignancy. We examined its effect on posttransplantation urothelial carcinoma (UC). METHODS: This retrospective case analysis included renal allograft recipients with UC treated with SRL in a single institute. RESULTS: Among 90 renal recipients treated with SRL, 6 had previous/new-onset UC in the native kidney/ureter or bladder: at a mean period of 28 months (range, 7-49) of administering SRL for these recipients, UC occurred/recurred in 4 of the 6 patients. Individual cases are presented in detail. CONCLUSION: SRL does not absolutely abolish the occurrence/recurrence of UC among renal transplant recipients. Its potency as an anti-cancerous immunosuppressant for transplant recipients with UC deserves to be further defined in larger studies, probably by controlling SRL blood levels at lower or much higher ranges than used herein.

Acute lobar nephronia in a renal allograft: a case report and literature review.

We report a diabetic renal transplant recipient who presented with fever and right lower quadrant abdominal pain. Acute appendicitis was considered initially and she underwent emergent appendectomy. However, persistent symptoms postoperatively made us perform an imaging study to identify the problems. Abdominal and pelvic computed tomography disclosed several focal wedge-shaped lesions of low attenuation in the renal allograft. Acute lobar nephronia was successfully managed with parenteral antibiotics. The patient recovered without any sequela. A renal allograft in the right iliac fossa complicates the diagnosis among acute renal infection, malignancy, acute rejection, and even acute appendicitis. Biopsy of the renal allograft is sometimes needed due to clinically ambiguous imaging results. In this report, we not only detail the clinical course of such a rare case, but also review the previous 3 cases of acute lobar nephronia in renal allografts in the literature.

The impact of human ABO blood groups on human xenoreactive antibody-mediated cytotoxicity and the protective effect of human decay-accelerating factors exogene on swine endothelium.

UNLABELLED: Swine tissue can express antigens similar to human A/B blood types. We evaluated whether the variation in human blood type influences the human xenoreactive antibody-mediated cytotoxicity and modifies the protective effect of human decay-accelerating factor (hDAF) exogene, a complement activation regulator, on swine endothelium. METHODS: Pig aortic endothelial cells were harvested form normal and hDAF transgenic pigs. Cellular viability was evaluated with an MTT assay. RESULTS: As compared with that of other human blood types, human serum from blood type O donors induced more prominent cytotoxicity on swine endothelial cells both from hDAF transgenic or normal pigs (P < .05). In addition, this difference of xenoreactive antibody-induced cytotoxicity between treatment with O and other human blood type sera was more evident in hDAF transgenic swine endothelial cells than those of normal pigs (P < .05). The hDAF exogene can significantly protect the endothelial cells from human xenoreactive antibody-mediated cytotoxicty when treated with human serum from AB blood type (P < .05). Our data demonstrated that human ABO blood type significantly affected human xenoreactive antibody-induced cytotoxicity, which may modulate the protective effect of hDAF exogene expression on swine endothelial cells.

Long-term survival of HLA-DR15+ pig skin in SCID mice after reconstitution with human peripheral blood mononuclear cells and under short-term immunosuppression.

In allotransplantation, donor-recipient human leukocyte antigen (HLA) matches improve graft survival. For studies of the role of donor-recipient HLA II matching on xenotransplantation, we successfully generated HLA-DR15+ transgenic pigs the the skins of which were transplanted to SCID mice, which were thereafter reconstituted with HLA-DR15+ or -DR15(-) hPBMC. Cyclosporine was given intraperitoneally to SCID mice for 12 days. Human T cells were observed in SCID mice after reconstitution. Mixed lymphocytes responses showed greater responses by HLA-DR15(-) human peripheral blood mononuclear cells (hPBMC) against HLA-DR15+ porcine PBMC. HLA-DR15+ porcine skins survived more than 100 days in all SCID mice. HLA-DR15+ porcine skins were rejected in all non-SCID (Balb/c) mice. The histologic pictures of transplanted HLA-DR15+ porcine skins showed surviving porcine epithelium in remodeling murine dermis and little lymphocyte infiltration into the murine dermis. The long-term survival of HLA-DR15+ pig skin in all hPBMC-SCID mice might be due to poor engraftment or function of reconstituted T cells. Further studies are needed to clarify the role of donor-recipient matching of HLA-DR15.

Human leukocyte antigen-DR matching improved skin graft survival from transgenic pigs to accommodate SCID mice reconstituted with human peripheral blood mononuclear cells.

The shortage of human organs has encouraged scientists to develop genetically modified pigs for xenotransplantation, such as CD55 or CD46, and CD59 transgenesis as well as alpha-galactosyl transferase gene knockouts. In allotransplantation, the match of human leukocyte antigen class II (HLA-II) may improve graft survival although the role of HLA-II in xenotransplantation is unknown. HLA-II transgenic pigs, including DP, DQ, and DR, have been successfully generated and HLA-DR15+ transgenic pig skin pieces grafted onto severe congenital immunodeficiency (SCID) mice reconstituted intraperitoneally with HLA-DR15+ or HLA-DR15(-) human peripheral blood mononuclear cells (hPBMCs). This study sought to develop an animal model to evaluate the effects of HLA-DR matching on xenograft survival. Human CD4+ and CD8+ were detected from days 7 to 29 after hPBMC reconstitution in SCID mice. Both CD4+ and CD8+ cells of HLA-DR15(-) reconstituted SCID mice were significantly higher at day 29 postgrafting compared with HLA-DR15+ reconstituted SCID mice. An HLA-DR15+ transgenic pig dermal graft survived and integrated into SCID mice reconstituted with hPBMCs/HLA-DR15+ as proven by the histopathological finding that the collagen layer remained intact with little lymphocytic response. In contrast, the transgenic pig dermal graft showed more collagen disruption as well as mild to moderate lymphocytic infiltration when reconstituted in an hPBMC/HLA-DR15(-) SCID mouse. The results suggested that HLA-DR matching eased xenograft rejection; however, it was not yet clear that the response was mediated by T cells.

The hDAF exogene protects swine endothelial and peripheral blood mononuclear cells from xenoreactive antibody mediated cytotoxicity in hDAF transgenic pigs.

Xenoreactive antibody-induced complement activation and cytotoxicity poses a major obstracle to xenograft survival in humans. Previously, we have generated transgenic pigs carrying the hDAF exogene to help overcome this problem. In this study, we examined whether the hDAF exogene in various swine cells shows an equally protective effect for the complement-mediated cytotoxicity induced by human xenoreactive antibodies. Pig peripheral blood mononuclear cells (PBMCs) and aortic endothelial cells (PAECs) were used as targets. Fresh human serum was harvested from a single healthy human donor as the source of human xenoreactive antibodies and complement. The target cells cocultured with medium containing various concentrations of human serum for 24 hours were evaluated using the 3-[4,5-dimethylthiaolyl]-2,5-diphenyl-tetrazolium bromide assay for cellular viability. We observed that xenoreactive antibody plus human complement-mediated cellular cytoxicity dose-dependently correlated with the concentration of human serum in the culture medium. As compared with the PBMCs from the normal pigs, PBMCs from hDAF transgenic pigs showed significantly better survival after treatment with human serum (P < .05). Similarly, the survival of PAECs from the hDAF transgenic pig were also significantly higher than that from normal pigs (P < .05). Our data demonstrated a protective effect from human xenoreactive antibodies and complement-mediated cytoxicity of hDAF exogenes in pig PBMCs and PAECs. These observations support the clinical value of the hDAF transgenic pig as an organ donor in xenotransplantation.

Lower urinary tract symptoms in female patients with rheumatoid arthritis.

OBJECTIVE: Patients with autoimmune diseases such as systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) are associated with an increased severity of lower urinary tract symptoms (LUTS). Recent surveys also reveal that rheumatoid arthritis (RA) is prevalent in patients with interstitial cystitis (IC). Therefore, we have investigated LUTS in patients with RA. METHODS: A total of 198 female patients with RA, aged 40 years or older, from the rheumatology outpatient clinic completed this prospective study. The American Urological Association Symptom Index (AUASI) score was used to assess the severity of LUTS and the O'Leary-Sant Symptom Index (ICSI) was used to evaluate IC-like urinary symptoms in these patients, which were compared to those of 679 age-matched controls. The possible associations of clinical parameters with LUTS were also explored. RESULTS: The Mean AUASI score and the percentage of individuals reporting severe LUTS (AUASI score > or = 20) or IC-like urinary symptoms (ICSI score > or = 12) showed no significant differences between the RA and control groups. However, in the RA group multivariate regression analyses identified patients with secondary SS (n = 21) to be associated with a significantly higher AUASI score (p = 0.007) and a higher percentage of severe LUTS (p = 0.02); these were also significantly higher than those of the control group (p = 0.02 and p = 0.01, respectively). CONCLUSION: Patients with RA have similar urinary complaints when compared to controls. However, those with secondary SS have a greater severity of LUTS, a finding similar to that observed in patients with primary SS.

Acute and chronic phase platelet aggregability studies in Chinese patients after implantation of a permanent transvenous pacemaker.

It has been suggested that the incidence of thromboembolic events always increases in patients after insertion of a transvenous pacemaker. Blood samples from twenty consecutive patients (fifteen males and five females) before and after pacemaker implantation was retained for platelet aggregability studies which were analyzed separately with ADP, collagen, epinephrine and arachidonic acid. The maximal amplitude of platelet aggregatory curve was detected by an aggregometer. The samples collected the day before pacemaker implantation (day 0) were used as self-control. Day 1 and day 3 after pacemaker implantation were defined as the acute phase, while day 30 was defined as the chronic phase. The maximal amplitude of platelet aggregatory curve was observed to be lowest on day 1 and then return to normal on day 3 and day 30. The results of platelet aggregability, however, showed no significant difference (P>0.05) between self-control and post-implantation samples. In conclusion, there was no significant change in platelet aggregability for either acute or chronic phases after pacemaker implantation. Antiplatelet medications may not be necessary for the prevention of thromboembolic events after the implantation of a pacemaker.

Methods for the study of nerve cell migration and patterning.

Recent advances in our ability to microfabricate tissue culture environments (1), and to store and retrieve microscopy data in a digital format, have made it increasingly possible to study fundamental aspects of neuronal migration and response to environmental cues. Neuronal migration refers to the migration of the growth cone at the tip of an extending neurite, a process that guides the neurite to its destination during neural development and regeneration (2). This chapter describes techniques for the observation of neuronal migration on both plain and patterned surfaces through the use of high-resolution, phase-contrast videomicroscopy. These techniques are particularly appropriate for analyzing the dynamics of single growth cone behavior in the presence of two-dimensional environmental microfeatures similar in scale to the growth cone dimensions (1-50 µm). Growth cone response to topographical features (3) or other three-dimensional environments are beyond the scope of this chapter. Substrate preparation procedures are derived from microlithography techniques first used in the microelectronics industry and adapted to cell culture systems (4-7). Glass cover slips are used as the substrate support to provide the required optical clarity for high-resolution microscopy, and patterns are created using laminin or collagen.

Neurite outgrowth and growth cone morphology on micropatterned surfaces.

The quantitative effects of micropatterned laminin surfaces on neurite outgrowth and growth cone morphology were investigated. Using microlithography, 20- or 30-micron-wide laminin stripes were applied to the surface of a glass coverslip, alternating with BSA-coated glass stripes of the same dimension. Growth on these surfaces was strongly biased in the direction parallel to the stripes, but the mean length of outgrowth was reduced relative to that on uniform laminin surfaces. Growth cones were slightly more elongated on micropatterned surfaces than on controls and were aligned with the pattern. These results provide a starting point for examining the fundamental effects of micropatterned surfaces on neurite outgrowth and ways in which these may be useful in controlling and guiding neurite outgrowth for biotechnological applications.

Influence of hydroxyapatite particle size on bone cell activities: an in vitro study.

Over the past decade, a large number of biomaterials have been proposed as artificial bone fillers for repairing bone defects. The material most widely used in clinical medicine is hydroxyapatite. The aim of our investigation was to study the effect of hydroxyapatite size mechanism on osteoblasts. The osteoblasts were cultured in vitro with 0.1% (1 mg/mL) of various sized hydroxyapatite particles (0.5-3.0, 37-63, 177-250, and 420-841 microm) for 1 h, 3 h, 1 day, 3 days, and 7 days. The results showed that adding hydroxyapatite particles to osteoblast cultures can significantly affect osteoblast cell count. Osteoblast populations decreased significantly. Osteoblast mean surface areas also changed significantly. Transforming growth factor-beta1 (TGF-beta1) concentrations in culture medium decreased significantly with the addition of hydroxyapatite particles. Prostaglandin E2 (PGE2) concentrations in medium increased significantly. The changes in TGF-beta1 and PGE2 concentration were more significant and persisted longer in smaller-particle groups. The inhibitory effects of hydroxyapatite particles on osteoblast cell cultures were mediated by the increased synthesis of PGE2. Caution should be exercised before using a hydroxyapatite product which could easily break down into fine particles.

Biocompatibility and osteoconductivity of the pyrost bone substitutes.

The purpose of this study was to re-evaluate the bone regeneration power and the in vitro biocompatibility of the Pyrost bone substitute. Twenty-four adult New Zealand White rabbits were used. Bony defect over both iliac crest and mid-diaphyseal portion of the ulna bone were created. Appropriate sized-block of Pyrost bone substitute were implanted. Four of the animals were killed at each postoperative month to evaluate its bone regeneration power by histologic study. The Pyrost bones were co-cultured with osteoblasts to evaluate its biocompatibility. The results showed that Pyrost bone substitute was quite stable and incorporated well with active bone regeneration. The Pyrost heal better at the iliac crest than at the ulnar defect. The Pyrost was compatible to the osteoblasts. Osteoblasts had successfully seeded and mitotically expanded on the porous surface of the Pyrost bone graft. The result showed that Pyrost bone obviously exerts an intense stimulus on osteo-regeneration in the presence of osteoblasts. We consider Pyrost to be an alternate to the conventional preserved allografts that is occasionally necessary.