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   

Improved intracranial lesion characterization by tissue segmentation based on a 3D feature map

Our aim was to develop an accurate multispectral tissue segmentation method based on 3D feature maps. We utilized proton density (PD), T₂-weighted fast spin-echo (FSE), and T₁-weighted spin-echo images as inputs for segmentation. Phantom constructs, cadaver brains, an animal brain tumor model and both normal human brains and those from patients with either multiple sclerosis (MS) or primary brain tumors were analyzed with this technique. Initially, misregistration, RF inhomogeneity and image noise problems were addressed. Next, a qualified observer identified samples representing the tissues of interest. Finally, k-nearest neighbor algorithm (k-NN) was utilized to create a stack of color-coded segmented images. The inclusion of T₁ based images, as a third input, produced significant improvement in the delineation of tissues. In MS, our 3D technique was found to be far superior to that based on any combination of 2D feature maps (P < 0.001). We identified at least two distinctly different classes of lesions within the same MS plaque, representing different stages of the disease process. Further, we obtained the regional distribution of MS lesion burden and followed its changes over time. Neuropsychological aberrations were the clinical counterpart of the structural changes detected in segmentation. We could also delineate the margins of benign brain tumors. In malignant tumors, up to four abnormal tissues were identified: 1) a solid tumor core, 2) a cystic component, 3) edema in the white matter, and 4) areas of necrosis and hemorrhage. Subsequent neurosurgical exploration confirmed the distribution of tissues as predicted by this analysis.     

The role of nuclear medicine in oncology

Nuclear Medicine offers screening methods for oncology such as bone and bone marrow scintigraphy. During the last two decades, special procedures have gained widespread application. This paper is centered around the “tumor-specific” radiopharmaceuticals. In patients with thyroid cancer, I-131 still plays a significant role. Ga-67 still has its indications in lymphoma, while in other diseases Tl-201 cloride is now the agent of choice. Especially in thyroid cancer, Tl-201 has proved to be a reliable tumor imaging radiopharmaceutical. More recently, Tc-99m MIBI was introduced for tumor imaging. Tc-99m HMPAO may also be used for tumor scintigraphy, especially in brain lesions. In addition, I-123 IMP has successfully been used for imaging malignant melanoma. Another promising field of tumor diagnosis is receptor imaging. In neuroblastoma and malignant pheochromocytoma, I-131/123 mIBG is the radiopharmaceutical of choice and may be considered as a receptor imaging agent also. First clinical results with In-111 octreotide show potentials as somatostatine-receptor radiopharmaceutical in insulinoma, islet cell carcinoma, medullary and lung cancer, while I-123 estradiol needs some improvement until it may be recommended as diagnostic tool in breast cancer. Since 1978, radiolabeled poly- or monoclonal tumor antibodies and their fragments have gained widespread application. Especially the Tc-99m 225.28S melanoma antibody, I-131 or Tc-99m CEA and In-111/I-131 labeled OC-125 antibodies have proven to be of clinical significance in melanoma, colorectal and ovarian cancer.