Enhancement of transdermal delivery of 6-beta-naltrexol via a codrug linked to hydroxybupropion.

Naltrexone (NTX) is a potent opioid antagonist used in the treatment of alcohol dependence and heroin abuse. Compared with naloxone, NTX has a longer duration of action largely attributed to its major active metabolite, 6-beta-naltrexol. The purpose of this study was to increase the delivery of 6-beta-naltrexol across human skin in vitro via a novel codrug. A carbonate codrug of 6-beta-naltrexol linked to hydroxybupropion was synthesized and evaluated. In vitro human skin permeation rates were measured using a flow-through diffusion cell system. The drug melting points, solubilities, chemical stability, and skin disposition were determined. The carbonate codrug was hydrolyzed on passing through skin and appeared as a combination of intact codrug and parent drugs, 6-beta-naltrexol and hydroxybupropion, in the receiver solution. The codrug provided a significantly (p<0.05) higher 6-beta-naltrexol flux across human skin than 6-beta-naltrexol base. The extent of parent drug regeneration in the skin ranged from 56 to 86%. A higher stratum corneum partition coefficient and rapid bioconversion of the carbonate codrug in the skin correlated with increased 6-beta-naltrexol delivery rates.     

Pulsed mode versus near-continuous mode delivery of diode laser photocoagulation for high-risk retinopathy of prematurity.

OBJECTIVE: To compare structural and functional outcomes and efficiency of diode laser photocoagulation for retinopathy of prematurity (ROP) when delivered in a pulsed mode versus a near-continuous mode. METHODS: A retrospective study was conducted of 138 patients who underwent diode laser photocoagulation for threshold ROP using either pulsed or near-continuous delivery. Laser-related complications and structural and functional outcomes were analyzed. Prospectively, time efficiency and total energy used were evaluated in nine infants with bilateral symmetric high-risk prethreshold ROP in which one eye of each infant was randomized to pulsed and the fellow eye to near-continuous delivery. RESULTS: There was no significant difference between groups with regards to prevalence of posterior disease (Zone 1 or posterior Zone 2) (p = 0.11), postoperative vitreous haze (p = 0.60), postoperative complications (p = 0.38), retinal detachment (p = 0.90), strabismus (p = 0.73), amblyopia (p = 0.69), or refractive error (p = 0.95). Mean time for treatment was 23 minutes using pulsed delivery versus 14 minutes per eye with near-continuous delivery (p < 0.001). The mean total power used per eye with pulsed mode delivery was 1.5 x 10(5) W versus 1.1 x 10(5) W with near-continuous delivery (p = 0.015). CONCLUSIONS: No differences in complications, functional outcome, or structural outcome were found between using pulsed mode and near-continuous mode diode laser delivery for high-risk ROP. Near-continuous laser delivery, in our hands, was more time-efficient and used less total power.     

A suggested clinical score to predict the severity of adenoid obstruction in children

Chronic nasal obstruction in children is a very common disorder. Obstructing adenoid is usually the first to blame. Though the clinical assessment is essential, it is often considered unreliable or insufficient. We conducted a prospective clinical study to validate a clinical score predicting the severity of adenoid obstruction in symptomatic children. The clinical score (CS) included mouth breathing, snoring, restless sleep, frequent waking-up at night and obstructive breathing during sleep. Each item received a score of 0 or 1. The palatal airway was evaluated on a lateral nasopharyngeal x-ray. The degree of obstruction was assessed intra-operatively by a laryngeal mirror using a 3-grade scale. The volume of each adenoid specimen was measured. Eighty-six patients were enrolled, 51 boys and 35 girls, aged 13–181 months (mean 52, median 45). The CS correlated very well with the intra-operative findings (p < 0.01) and with the degree of palatal airway obstruction (p < 0.05) but not with the volume of the adenoid removed (p > 0.05). The CS was higher in children younger than 3 years (CS > 3 in 85.7% vs. 29.2%), having more frequent obstructive breathing during sleep (71.43% vs. 21.54%). A CS of three or higher, predicted severe obstruction in 96.5% of patients, as detected intra-operatively. The suggested CS is simple to use and is highly reliable in identifying children in need for adenoidectomy, in the context of normal anterior rhinoscopy and tonsils less than grade three.This work was presented at the podium of the XVIII IFOS in Rome, Italy on June 26, 2005.     

The impact of mitral valve morphology on the long-term outcome of mitral balloon valvuloplasty.

BACKGROUND: The effect of mitral valve morphology (MVM) on the long-term results of mitral balloon valvuloplasty (MBV) is not well established. The aim of the study was to evaluate the impact of MVM on long-term outcome of MBV. METHODS: Five hundred and eighteen consecutive patients (mean age, 31+/-11 years) who underwent successful MBV were followed up for 0.5-16.5 (mean, 6+/-4.5) years. Patients were divided into two groups according to their mitral echo score (MES) before MBV: group A (n=340; MES8). RESULTS: We report the immediate and long-term clinical and echocardiographic results of the above-mentioned 518 consecutive patients. The mitral valve area was significantly larger in group A than in group B, both immediately after MBV (2.0+/-0.3 vs. 1.82+/-0.3 cm2, respectively; P<0.0001) and also at the last follow-up (1.8+/-0.33 vs. 1.5+/-0.33 cm2, respectively; P<0.0001). Restenosis occurred in 38/340 (11%) in group A vs. 73/178 (41%) in group B (P<0.0001). Actuarial freedom from restenosis at 5, 10, 15 years were 92+/-2%, 85+/-3%, 65+/-6% for group A vs. 72+/-4%, 44+/-5%, 9+/-6% for group B (P<0.001). Event-free survival rates at 5, 10, 15 years for group A were 93+/-1%, 88+/-2%, 66+/-6% vs. 82+/-3%, 59+/-6%, 8+/-7% for group B (P<0.0001). Stepwise Cox multivariate regression analysis identified MES, preprocedure functional class, and postprocedure mitral valve area相似文献   

Presence of human papillomavirus DNA and abnormal p53 protein accumulation in lung carcinoma.

BACKGROUND: In some carcinomas inactivation of the tumour suppressor gene product p53, either by point mutation or indirectly by the human papillomavirus (HPV), has been suggested as two alternative routes to malignant transformation. To test this hypothesis in lung tumours, 43 lung carcinomas were analysed by in situ hybridisation and polymerase chain reaction (PCR) for the presence of HPV DNA, and the results were compared with p53 protein immunohistochemical analysis. METHODS: The presence of HPV DNA in lung carcinoma was detected by nucleic acid in situ hybridisation for HPV types 6, 11, 16, 18, 31, and 33 using nonradioactively labelled DNA probes. Polymerase chain reaction (PCR) analysis was performed on all cases showing positive HPV DNA labelling by in situ hybridisation and in an additional 13 negative cases. Abnormal nuclear accumulation of the p53 protein was revealed by immunohistochemistry using the avidin-biotin-peroxidase complex method and a CM-1 polyclonal anti-human p53 antibody and a monoclonal mutation-specific Pab 240 p53 antibody. RESULTS: HPV DNA was found by in situ hybridisation in 13 lung carcinomas (30%). In all these cases subtype-specific HPV DNA could also be detected by PCR. Abnormal p53 protein accumulation was seen in 21 of the 43 carcinomas (49%), of which 18 were HPV negative. Twelve (57%) of the CM-1 positive cases were also positive for the mutation-specific antibody Pab 240. There was an obvious inverse relationship between the presence of papilloma viral DNA and abnormal p53 protein accumulation. CONCLUSIONS: p53 plays an important part in the development of lung carcinomas and, in some cases, HPV may contribute to it by binding and inactivating the p53 protein.