Protected carotid stenting in high-surgical-risk patients: the ARCHeR results

BACKGROUND: Carotid endarterectomy is the standard of care for most patients with severe extracranial carotid bifurcation disease. However, its safety and efficacy in patients with significant surgical risk are unclear. The ARCHeR (ACCULINK for Revascularization of Carotids in High-Risk patients) trial was performed to determine whether carotid artery stenting with embolic protection is a safe and effective alternative to endarterectomy in high-surgical-risk patients. METHODS: The ARCHeR trial is a series of three sequential, multicenter, nonrandomized, prospective studies. Forty-eight sites enrolled 581 high-surgical-risk patients between May 2000 and September 2003. Patients with severe carotid artery stenosis (angiographically defined, symptomatic > or =50%, or asymptomatic > or =80%) had an ACCULINK nitinol stent implanted. The ACCUNET filter embolic protection system was added to the procedure in the final 2 studies (422 patients). The primary efficacy end point was a composite of periprocedural (< or =30 days) death, stroke, and myocardial infarction, plus ipsilateral stroke between days 31 and 365. RESULTS: The 30-day rate of death/stroke/myocardial infarction was 8.3% (95% confidence interval [CI], 6.2%-10.8%), and that of stroke/death was 6.9% (95% CI, 5.0%-9.3%). Most (23/32) strokes were minor, of which more than half (12/23) returned to baseline National Institutes of Health Stroke Scale scores within 30 days. The 30-day major/fatal stroke rate was 1.5% (95% CI, 0.7%-2.9%). No hemorrhagic strokes were observed in the study. Ipsilateral cerebrovascular accident occurred in 1.3% between 30 days and 1 year, thus giving a primary composite end point of 30-day death/stroke/myocardial infarction plus ipsilateral stroke at 1 year of 9.6% (95% CI, 7.2%-12.0%), which is below the 14.4% historical control comparator. Target lesion revascularization at 12 months and 2 years was 2.2% and 2.9%, respectively. CONCLUSIONS: The ARCHeR results demonstrate that extracranial carotid artery stenting with embolic filter protection is not inferior to historical results of endarterectomy and suggest that carotid artery stenting is a safe, durable, and effective alternative in high-surgical-risk patients.     

Carriage of methicillin-resistant Staphylococcus aureus in a Queensland Indigenous community

OBJECTIVE: To determine the prevalence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) carriage and infection among children living in an Indigenous community in Queensland. DESIGN, SETTING AND PARTICIPANTS: Swabs for culture of S. aureus were collected from the nose, throat and skin wounds of primary school children. MAIN OUTCOME MEASURES: MRSA carriage, antibiotic sensitivity, genotype, and presence of the virulence factor Panton-Valentine leukocidin (PVL); and epidemiological risk factors for MRSA carriage. RESULTS: 92 (59%) of 157 eligible children were included in the study. Twenty-seven (29%) carried S. aureus; 14 of these (15% of total) carried MRSA. MRSA was isolated from 29% of wound swabs, 8% of nose swabs, and 1% of throat swabs. Fourteen of 15 MRSA isolates were sensitive to all non-beta-lactam antibiotics tested. Eight children (9%) carried CA-MRSA clonal types: six carried the Queensland clone (ST93), and two carried the South West Pacific clone (ST30). All these isolates carried the virulence factor PVL. The remaining six children carried a hospital-associated MRSA strain (ST5), negative for PVL. CONCLUSIONS: We have identified a high prevalence of CA-MRSA carriage in school children from a Queensland Indigenous community. In this setting, antibiotics with activity against CA-MRSA should be considered for empiric therapy of suspected staphylococcal infection. Larger community-based studies are needed to improve our understanding of the epidemiology of CA-MRSA, and to assist in the development of therapeutic guidelines for this important infection.     

Lipid microparticles for mucosal immunization against hepatitis B

Parenteral administration of vaccines often does not lead to optimal or long lasting protection against disease causing organisms particularly those that are inhaled, ingested or sexually transmitted. For optimal mucosal protection induction of immune response via mucosal routes is therefore highly desirable. Double emulsion-solvent evaporation (w/o/w) method best suited for water-soluble bioactives was selected for the preparation of hepatitis B surface antigen (HBsAg) loaded lipid microparticles. Intranasal route was considered for mucosal administration and hence to prepare the delivery system biocompatible and least irritable, soyalecithin (phospholipid) was taken instead of polymer because phosphatidylcholine is the major component of endogenous lung surfactant. The studies performed in present work included antigen characterization, development of lipid microparticles, stability studies of the prepared lipid microparticle formulations, percent mucoadhesion, ex vivo cellular uptake studies and in vivo studies. The general order obtained from in vivo studies for mucosal immune response (IgA) followed the sequence: LMST-HBsAg (IN)>LM-HBsAg (IN)>alum-HBsAg (IN)>LMST-HBsAg (IM)>alum-HBsAg (IM)>or=LM-HBsAg (IM)>plain HBsAg (IN)>plain HBsAg (IM).     

Lithium inhibits internalization and endosomal processing of both neuropeptide Y (NPY) Y1 and transferrin receptors

Low concentrations of Li+ reduce the rate of internalization of neuropeptide Y (NPY) Y1 receptors [M.S. Parker, S.L. Parker, J.K. Kane, Internalization of neuropeptide Y Y1 and Y5 and of pancreatic polypeptide Y4 receptors is inhibited by lithium in preference to sodium and potassium ions, Regul. Pept., 118 (2004) 67-74]. This Li+-induced decrease in Y1 receptor internalization could be alleviated by Y1 receptor agonists. As shown by fractionation on Percoll gradients, lithium treatment induces a concentration-related decrease of intermediate and higher endosomal densities that contain the internalized Y1 ligand-receptor complex. This indicates an inhibition of endosome processing and maturation. Internalization of human transferrin shows [Li+] sensitivity similar to that of the Y1 receptor, and a similar Li+-induced decrease in endosomal processing. Lithium treatment thus decreases activity of the endosome system shared in the recycling endocytosis of the Y1 and transferrin receptors.     

FDA policy on unapproved drug products: past, present, and future

OBJECTIVE: To review the history of drug regulation by the Food and Drug Administration (FDA) as it relates to unapproved drugs and FDA policy, along with the FDA's efforts to avoid future incidents by amending and enforcing those policies that are already in place. DATA SOURCES: Data from FDA history documents, FDA guidances, Code of Federal Regulations Title 21, and presentations by the FDA's Office of Compliance were gathered. STUDY SELECTION AND DATA EXTRACTION: All information identified from the data sources was evaluated, and all information deemed relevant was included for this review. DATA SYNTHESIS: Contrary to popular belief, there are drugs on the market that have not been evaluated for safety or efficacy by the FDA. For almost a century, the FDA has taken action against public health threats posed by unapproved drug products, and today's drugs and vaccines are required to demonstrate both safety and efficacy prior to marketing. The FDA has taken great strides to ensure the welfare of Americans by reacting to disasters that have occurred in the past and being proactive by setting regulations that will prevent such catastrophes from occurring in the future. CONCLUSIONS: The FDA recognizes that drug regulation is an ongoing process and that, although we have come a long way, there is still much to be done.     

Association of CCR5 human haplogroup E with rapid HIV type 1 disease progression

The combination of unique single nucleotide polymorphisms in the CCR5 regulatory and in the CCR2 and CCR5 coding regions, defined nine CCR5 human haplogroups (HH): HHA-HHE, HHF*1, HHF*2, HHG*1, and HHG*2. Here we examined the distribution of CCR5 HH and their association with HIV infection and disease progression in 36 HIV-seronegative and 76 HIV-seropositive whites from North America and Spain [28 rapid progressors (RP) and 48 slow progressors (SP)]. Although analyses revealed that HHE frequencies were similar between HIV-seronegative and HIV-seropositive groups (25.0% vs. 32.2%, p > 0.05), HHE frequency in RP was significantly higher than that in SP (48.2% vs. 22.9%, p = 0.002). Survival analysis also showed that HHE heterozygous and homozygous were associated with an accelerated CD4 cell count decline to less than 200 cells/microL (adjusted RH 2.44, p = 0.045; adjusted RH = 3.12, p = 0.037, respectively). These data provide further evidence that CCR5 human haplogroups influence HIV-1 disease progression in HIV-infected persons.     

Successful treatment of extensive basidiobolomycosis with oral itraconazole in a child

BACKGROUND: Basidiobolomycosis is a rare chronic subcutaneous infection caused by Basidiobolus ranarum, which is usually treated with potassium iodide. Extensive deforming lesions in children can occur owing to lack of early diagnosis and/or inappropriate treatment. CASE REPORT: An 8-year-old girl child presented to us with extensive deforming plaque-like lesions over the left thigh and leg with multiple ulcerations of 1 year's duration. Histopathology was suggestive of subcutaneous zygomycosis with Splendore Hoeppli phenomenon. Microscopic examination of the tissue showed branching, sparsely septate fungal hyphae on a 10%KOH mount, and culture yielded Basidiobolus ranarum. The patient was initially treated with potassium iodide for 6 weeks to which only a poor response was observed. Itraconazole therapy resulted in rapid regression of the lesions and complete resolution after 15 weeks of therapy. She continues to be disease-free at 1 year of follow up. CONCLUSIONS: This case report highlights that in an older child even longstanding extensive basidiobolomycosis can be safely treated with itraconazole. Surgery is not usually necessary in these patients.     

Evaluation of glyceryl trinitrate, misoprostol, and prostaglandin E2 gel for preinduction cervical ripening in term pregnancy

AIM: To compare the efficacy of glyceryl trinitrate (GTN), dinoprostone and misoprostol for preinduction cervical ripening in primigravida at term. METHODS: Sixty-five term primigravida, each with an unfavorable cervix (Bishop score 6) in a greater proportion of subjects in the misoprostol (n = 18, 81.8%) and dinoprostone (n = 14, 66.7%) groups compared with the GTN group (n = 11, 55%). In subjects with a severely unfavorable cervix (Bishop score 相似文献