In utero transplantation of human fetal haemopoietic cells in NOD/SCID mice

BACKGROUND: Carotid angioplasty (CA) has been suggested to be a safer and more cost-effective alternative to carotid endarterectomy (CEA) in the management of symptomatic severe internal carotid artery (ICA) disease. METHODS: The study was conducted as a prospective consecutive randomized trial of CEA versus CA for symptomatic severe ICA disease in a university teaching hospital. All patients were assessed before and after surgery by a neurologist. The study consisted of 23 patients with focal carotid territory symptoms and severe ICA stenosis (> 70%) who were randomized to either CEA or CA. However, only 17 had received their allocated treatment before trial suspension. CEA with patching or CA with stenting were used as interventions. The main outcome measures were death or disabling or nondisabling stroke within 30 days. RESULTS: All 10 CEA operations proceeded without complication, but 5 of the 7 patients who underwent CA had a stroke (P=.0034), 3 of which were disabling at 30 days. CONCLUSIONS: After referral, the Data Monitoring Committee invoked the stopping rule and the trial was suspended. The investigators and the Ethics Committee subsequently concluded that the trial could not be restarted--even in an amended format-primarily because of problems with informed consent. We review many of the ethical dilemmas encountered in the performance of this study. If future trials do suggest a selected role for CA, it is essential that both the inclusion and the exclusion criteria are fully documented.     

The effects of cochlear hearing loss, age and sex on the auditory brainstem response

This study analyzed the effects of auditory impairment, age and sex on the auditory brainstem response (ABR) wave latencies. ABR wave I, wave V and I-V interval measures were extracted from the clinical records of 201 patients with cochlear hearing loss. Females had consistently earlier wave V latencies and shorter I-V intervals than males. No age effects were observed. Degree of impairment had a systematic effect on ABR wave latencies and I-V intervals. Wave I displayed latency extension with increasing levels of high-frequency hearing loss, whilst for wave V increases in latency were dependent upon both degree and slope of the hearing loss. Present results suggest that many of the previously reported sex differences and variable interactions seen for the ABR can be accounted for by differences in the underlying distribution of audiogram shapes within and between study populations. Different audiometric configurations were found to produce consistent differential effects on both wave I and wave V latency and thus influence the I-V interval. This study underlines the need to develop a more detailed model of impairment effects if correction factors are to be employed more effectively in ABR testing for retrocochlear pathology.     

Inhibition of mitogen-activated protein kinase kinase blocks T cell proliferation but does not induce or prevent anergy

Three mitogen-activated protein kinase pathways are up-regulated during the activation of T lymphocytes, the extracellular signal-regulated kinase (ERK), Jun NH2-terminal kinase, and p38 mitogen-activated protein kinase pathways. To examine the effects of blocking the ERK pathway on T cell activation, we used the inhibitor U0126, which has been shown to specifically block mitogen-activated protein kinase/ERK kinase (MEK), the kinase upstream of ERK. This compound inhibited T cell proliferation in response to antigenic stimulation or cross-linked anti-CD3 plus anti-CD28 Abs, but had no effect on IL-2-induced proliferation. The block in T cell proliferation was mediated by down-regulating IL-2 mRNA levels. Blocking Ag-induced proliferation by inhibiting MEK did not induce anergy, unlike treatments that block entry into the cell cycle following antigenic stimulation. Surprisingly, induction of anergy in T cells exposed to TCR cross-linking in the absence of costimulation was also not affected by blocking MEK, unlike cyclosporin A treatment that blocks anergy induction. These results suggest that inhibition of MEK prevents T cell proliferation in the short term, but does not cause any long-term effects on either T cell activation or induction of anergy. These findings may help determine the viability of using mitogen-activated protein kinase inhibitors as immune suppressants.     

Mass spectrometric analysis of 2-deoxyribonucleoside and 2'-deoxyribonucleotide adducts with aldehydes derived from lipid peroxidation

An important emerging issue in chemical carcinogenesis is the role that products of endogenous metabolism play in formation of covalently modified DNA. One example is the formation of alpha, beta-unsaturated aldehydes as a result of endogenous and drug-stimulated lipid peroxidation. Malondialdehyde (MDA), crotonaldehyde (CR), 2-hexenal (HX), and 4-hydroxy-2-nonenal (HNE) react covalently with 2'-deoxyguanosine (dG) and 2'-deoxyadenosine (dA) residues on DNA to form promutagenic cyclic adducts that may be important in the etiology of cancer in humans and animals. The accurate quantification of such adducts provides a powerful tool in molecular epidemiology for assessing carcinogenic risks from various lifestyle choices (e.g. diet, drug use) in humans. 32P-Postlabeling is recognized as one of the most sensitive methods available for detection of DNA adducts in human tissues, but without adequate validation such methodology can yield inaccurate quantitative measurements. We have used LC separations in conjunction with electrospray ionization MS and tandem MS (triple quadrupole and hybrid quadrupole-orthogonal acceleration time of flight analyzers) to characterize MDA-, CR-, HX- and HNE-modified dG and nucleotide (3'- and 5'-monophosphate; 3',5'-bisphosphate) adducts. These data have been used to validate 32P-postlabeling methods for quantification of low level MDA-dG adducts formed in DNA of human and animal tissues. Availability of reliable methods for quantification of endogenous DNA damage in humans and animals is essential for determining unknown etiologies of cancer and for the assessment of cancer risks in humans.     

Biological characteristics of Ligusticum chuanxiong Hort

Observational studies were conducted on the biological characteristics of Ligusticum chuanxiong, such as suitable growth environment, growing period, growth of stems, leaves and rhizomes, yield structure, etc. The specific regularities of each growth period were also studied.     

Complicated right subclavian artery pseudoaneurysm after central venipuncture

Life-threatening complications of central venipuncture are rare. We report an unusual case of a patient in whom a large right subclavian pseudoaneurysm developed, causing pressure necrosis of the membranous trachea and esophagus, after right internal jugular vein cannulation. The patient underwent oversewing of the proximal and distal ends of the subclavian artery and primary tracheal repair. An esophageal leak that presented on the sixth postoperative day was treated by primary suture repair with proximal and distal diversion.     

Selective ET(A) receptor antagonism reduces neointimal hyperplasia in a porcine coronary stent model

BACKGROUND: As endothelin binds to ET(A) receptors, it stimulates vascular smooth muscle cell proliferation and may thus be pivotally involved in the pathogenesis of restenosis. This study assessed the ability of a potent and selective ET(A) antagonist to reduce neointimal hyperplasia in a porcine coronary artery stented injury model. METHODS AND RESULTS: Fifty-five pigs were randomized to receive placebo or the oral ET(A)-selective antagonist ABT147627 twice daily for 28 days in one of three doses: 0.75 mg/kg (low), 3.75 mg/kg (mid), and 10.0 mg/kg (high). Each underwent oversized stent deployment in two randomly assigned major epicardial coronary arteries. Three animals (5.5%) died as a consequence of stent thrombosis within 24 hours of the procedure. The remaining 52 animals (13 pigs per group) survived without complication until predetermined euthanasia at 28 days. In the placebo group, mean injury score was 1.73+/-0.80, with a mean neointimal response of 0.45+/-0.24 mm. By comparison, the low-dose group had a similar mean injury score of 1.79+/-0.75 with reduced neointimal response, 0.36+/-0.22 mm (P<0.01). Mean injury score in the mid-dose animals was significantly greater than in the placebo group (1.94+/-0.92; P<0.05). The neointimal hyperplasia associated with this injury was less than with placebo, although the difference did not reach statistical significance (0.40+/-0.25 mm; P=0.05). In the high-dose pigs, mean injury score was also significantly greater than in the placebo arm (1.93+/-0.73; P<0.05). Despite this, neointimal response was also significantly less (0.37+/-0.37 mm; P<0.01). CONCLUSIONS: Oral, selective ET(A) receptor antagonism significantly reduced neointimal hyperplasia forming over porcine coronary stented injuries in the first 28 days. This strategy may have clinical potential for the limitation and treatment of coronary restenosis after percutaneous revascularization.     

Long-term analysis of conventional coronary balloon angioplasty and an initial "stent-like" result. The NHLBI PTCA Registry

Researchers examining clinical decision-making often explored the role of the nurse's experience. In these studies, experience was conceptualized as either the time spent in nursing or the knowledge which came from practice. This paper reports on the conceptualization of the nurse's experience emerging from a grounded theory study describing one decision-making process: 'knowing the patient'. Data included in-depth interview text, participant observation fieldnotes, and documents. Data were analysed using the constant comparative method and open, axial and selective coding techniques. In the analysis, the nurse's experience was conceptually defined as 'the application of that learned from previous practice situations'. Three attributes of the nurse's experience emerged. These included a focus on the patient, confidence in practice, and knowledge of antecedents and consequences of similar patient situations. Each aspect enhanced the individualization of nursing interventions. The findings are related to other investigations in nursing and insights for practice are offered.