T-cell depletion and graft survival induced by anti-human CD3 immunotoxins in human CD3epsilon transgenic mice

BACKGROUND: Anti-CD3 immunotoxins are broad-spectrum immunosuppressive agents in a wide range of organ transplantation animal models with potential use in eliciting antigen-specific tolerance. However, the anti-CD3 immunotoxins used in animal studies do not cross-react with human T cells, limiting extrapolation to humans and hindering clinical development. METHODS: Three anti-human CD3-directed immunotoxins, DT389-scFv(UCHT1), scFv(UCHT1)-PE38, and UCHT1-CRM9, were compared in vitro and in transgenic mice, tg(epsilon)600+/-, that have T cells expressing both human and murine CD3epsilon antigens. RESULTS: These immunotoxins were extraordinarily potent in vitro against human or transgenic mouse T cells, with IC50 values in cellular assays ranging from pM to fM. Systemic administration of these immunotoxins dose-dependently depleted >99% of tg(epsilon)600+/- lymph node and spleen T cells in vivo. Depletion was specific for T cells. The loss of the concanavalin A-induced, but not the lipopolysaccharide-induced, splenic proliferative response from immunotoxin-treated animals further demonstrated specific loss of T-cell function. Immunotoxin treatment prolonged fully allogeneic skin graft survival in tg(epsilon)600+/- recipients to 25 days from 10 days in untreated animals. T-cells recovered to approximately 50% of normal levels after approximately 22 days in animals with or without skin grafts; T-cell recovery correlated with skin graft rejection. All three immunotoxins elicited >100 day median survival of fully allogeneic heterotopic heart grafts. By 100 days, T cells recovered to normal numbers in these animals, but the grafts showed chronic rejection. CONCLUSION: These immunotoxins profoundly deplete T cells in vivo and effectively prolong allogeneic graft survival.     

The Effect of Nutrient Intake on Bone Mineral Status in Young Adults: The Northern Ireland Young Hearts Project

Optimizing peak bone mass in early life may reduce osteoporosis risk in later life. Such optimization may be partly dependent upon diet. In the present study, nutrient intakes and selected lifestyle parameters were assessed in adolescent subjects (238 males, 205 females; aged 15 y) and again, in the same subjects, on one occasion in young adulthood (aged between 20 and 25 y). The extent of the relationships between these parameters and bone mineral density (BMD), dual energy X-ray absorptiometry (DXA), lumbar spine (L2-L4), and femoral neck measured concurrently with diet in young adulthood only, was assessed. Adjusted linear regression models were constructed. Variables included a measure of pubertal status (at age 15 y), age (at young adulthood), height, weight, physical activity, smoking, and mean daily intakes of energy, calcium, protein, vitamin D, phosphorus, total fat, and alcohol. In both sexes, body weight at adolescence and young adulthood was the only factor consistently positively associated with BMD at both measurement sites. Effects of nutrient intake on BMD were inconsistent. Vitamin D and calcium intakes reported by female adolescents showed significant positive relationships with BMD measured in young adulthood (vitamin D measured at the lumbar spine; calcium measured at the femoral neck). The positive relationship between vitamin D and BMD remained significant at young adulthood, but at the femoral neck rather than at the lumbar spine. Also in females, intakes of phosphorus and the calcium:phosphorus ratio (Ca:P) at adolescence were strongly negatively related to femoral neck BMD measured at young adulthood. In males, however, Ca:P reported at young adulthood had a significant positive relationship with lumbar spine BMD, whereas Ca:protein was negatively associated with BMD at the lumbar spine. Intakes of Ca reported by adolescent males also had a strong negative effect on lumbar spine BMD measured at young adulthood.     

Survival disparities in newborns with congenital diaphragmatic hernia: a national perspective

Purpose

The aim of the study was to examine national outcomes for congenital diaphragmatic hernia (CDH).

Methods

We analyzed the Kids' Inpatient Database for patients admitted at less than 8 days of age.

Results

Overall, 2774 hospitalizations were identified. Most patients were white and had private insurance. Most patients were treated at urban (96%), teaching (75%), and not identified as children's hospital (NIACH) (50%). Birth was the most common admission source at NIACH (91%) and children's unit in general hospital (CUGH) (59%), compared to hospital transfer at children's general hospital (CGH) (81%). Most CDH were repaired through the abdomen (81%), and 25% required extracorporeal membrane oxygenation (ECMO). Most NIACH patients were transferred to another hospital, whereas most at CGH and CUGH were discharged home. Survival to discharge was 66% after excluding hospital transfers. Univariate analysis revealed higher survival for males, birth weight (BW) of 3 kg or more, whites, patients with private insurance, and those in the highest median household income quartile. Survival was 86% after CDH repair but 46% for ECMO. Multivariate analysis identified black race (hazard ratio [HR], 1.536; P = .03) and other race (HR, 1.515; P = .03) as independent predictors of mortality.

Conclusions

Hospital survival for CDH is related to sex, BW, race, and socioeconomic status. Blacks and other non-Hispanic minorities have higher mortality rates.     

Endovascular repair of a common iliac artery aneurysm using the Cook Zenith abdominal aortic aneurysm Endovascular Graft Converter

Isolated common iliac artery aneurysm is a rare condition that is treated aggressively because of its high risk of rupture. Endovascular abdominal aortic aneurysm (AAA) repair has recently been extended to the clinical management of the iliac artery aneurysm. Stent grafts have been used successfully to exclude iliac artery aneurysms. Successful graft deployment and aneurysm exclusion require adequate seal and fixation at the proximal and distal attachment sites. This article presents a high-risk surgical patient whose 6.8-cm-diameter iliac artery aneurysm was repaired with a Zenith AAA Endovascular Graft Converter (Cook, Bloomington, Indiana). This device is normally used to convert an aortobiiliac endograft to an aortouniiliac endograft during AAA repair. The tapered 80-mm-long graft has diameters of 24 mm proximally and 12 mm distally. Completion arteriogram demonstrated exclusion of the iliac artery aneurysm with no evidence of endoleak. No postoperative complications occurred. No endoleak was seen on the follow-up abdominal computed tomography scan.     

Direct effects of propofol on myocardial and vascular tissue from mature and immature rats

OBJECTIVE: To determine the effect of age on the direct myocardial and vascular effects of propofol in rats. DESIGN: Randomized, prospective with repeated measures. SETTING: University research laboratory. PARTICIPANTS: Myocardial and aortic tissue from 12 immature (4-week-old) and 12 mature (16-week-old) male Sprague-Dawley rats. INTERVENTIONS: Change in force of contraction was measured in isolated myocardial strips or in isolated descending thoracic aorta rings during exposure to propofol or intralipid. MEASUREMENTS AND MAIN RESULTS: Propofol produced a dose-dependent decrease in vascular tone (p < 0.05). This effect was similar for intralipid. Propofol was more potent in the younger animals (EC(50), 5.3 microg/mL [confidence interval, 2.5 to 11.1] for 4-week-old and 26.6 microg/mL [confidence interval, 6.8 to 103.7] for 16-week-old rats; p < 0.05). In contrast, propofol produced a dose-dependent decrease in contractility (p = 0.001), whereas intralipid produced no decrease in contractility. CONCLUSIONS: Although propofol does produce a dose-dependent decrease in contractility, this effect is similar at different ages. Propofol produces more direct vascular relaxation in the immature tissue. Propofol's direct cardiovascular effect and its indirect cardiovascular effects should be considered in the young and old, especially when cardiovascular reserve is limited.     

Distal Venous Patch improves results in PFTE bypasses to Tibial arteries

In recent years, the management of limb-threatening ischemia has involved the use of distal bypasses to vessels beyond the popliteal trifurcation. Excellent patency rates and limb salvage data are achieved through the use of autologous long saphenous vein. However, an increasing number of patients in need of tibial bypass do not have adequate saphenous vein due to previous procedures, thrombophlebitis, or inadequate vein. In such cases alternative conduits have been proposed including lesser saphenous vein, arm vein, composite veins, composite vein with poly-tetrafluoroethylene (PTFE), and PTFE with or without a distal arteriovenous fistula. Unfortunately these alternative conduits have not resulted in equivalent results when used for distal bypass to tibial arteries. Several authors have reported upon the use of venous tissue at the distal anastomosis in the form of cuffs, collars, and boots to improve the results of prosthetic grafts in this challenging patient population. These techniques have been proposed as an option for revascu-larization in patients without adequate saphenous vein in an attempt to obtain limb salvage. The purpose of this review is to examine some of those techniques and focus on distal vein patch configuration with its perceived advantages and drawbacks.     

Qualitative comparison of sonic or laser energisation of 4% sodium hypochlorite on an Enterococcus faecalis biofilm grown in vitro

The effectiveness of sonic activation, laser activation and syringe irrigation of 4% sodium hypochlorite in removing an Enterococcus faecalis biofilm was compared. Biofilms were grown in extracted human single rooted teeth using a flow cell apparatus. After 4 weeks' growth, teeth were subjected to each treatment using 4% sodium hypochlorite and radicular dentinal surfaces of the root canals were analysed by scanning electron microscopy. Results showed that sonic activation and syringe irrigation with sodium hypochlorite showed reduced numbers of bacterial cells on the radicular dentine but were not effective in eliminating E. faecalis in the dentinal tubules. Laser activation of sodium hypochlorite resulted in clean dentine walls and undetectable levels of bacteria within dentinal tubules. Qualitatively, sonic or laser activation of 4% NaOCl resulted in greater bacterial reduction compared with syringe irrigation, with laser activation producing the greatest overall reduction.     

Visual-evoked potential evidence of chiasmal hypoplasia

PURPOSE: To show that chiasmal hypoplasia or aplasia need not be an isolated developmental anomaly and to examine the spectrum of associated clinical findings to explore the possibility that these patients may represent a phenotypic manifestation of a developmental gene anomaly. DESIGN: An observational case series. PARTICIPANTS: Five infants, between several weeks and 7 months of age, in whom the electrophysiologic characteristic of chiasmal hypoplasia had been noted were included. METHODS: Flash electroretinography and flash and pattern visual-evoked potentials (VEPs) were elicited from all patients. Clinical ophthalmologic examinations, including funduscopy, were performed, and all patients had magnetic resonance imaging (MRI) brain scans. MAIN OUTCOME MEASURES: The occipital distribution of monocular VEP response peaks was studied. The symmetry of lateral channel responses was compared for monocular stimulation. RESULTS: All five patients had a crossed asymmetry in the monocular VEP occipital distribution, which is consistent with a paucity of fibers crossing at the chiasm. The MRI findings supported this electrophysiologic observation, illustrating degrees of chiasmal hypoplasia and variable coincidence of other midline abnormalities of the brain. Optic disc appearances varied from normal to hypoplastic and colobomatous. CONCLUSIONS: The ophthalmologic and MRI findings of five patients who showed a crossed asymmetry in monocular flash VEPs are consistent with a paucity of axons crossing at the chiasm. The similarities between achiasmia in humans and mice due to a Pax2 gene anomaly are discussed.     

MR imaging of facial nerve enhancement in Bell palsy or after temporal bone surgery

The authors evaluated magnetic resonance (MR) images obtained with intravenously administered gadolinium in ten patients who had facial paralysis and no facial nerve tumor. In patients with either Bell palsy (four patients) or facial paralysis after temporal bone surgery (six patients), intratemporal facial nerve enhancement was seen. Facial nerve enhancement on MR images proved to be a nonspecific finding.