Transdermal permeation-enhancing activities of some inorganic anions

Effects of sodium salts of various monovalent inorganic anions on transdermal permeation of salicylic acid were investigated. In in-vitro experiment using a Franz-type diffusion cell and excised mouse skin, the permeation-enhancing activities of the sodium salts of inorganic anions were roughly proportional to lyotropic Hofmeister swelling abilities of the anions; F^?<SO₄ ^2?<Cl^? <ClO₄ ^?<NO₃ <SCN^? <Br <I^?, i.e. l, Br and SCN increased the flux of drugs through the mouse skin, while F^?, SO₄ ^2?, Cl^?, ClO₄ ^? and NO₃ ^? decreased or did not affect the flux. In invivo experiment using the rabbit as the test animal, the plasma concentration of salicylic acid of the rabbit to which 10%-salicylic acid ointment containing 5%-Nal or NaBr was applied was significantly higher than that of the rabbit to which the ointment without the electrolytes was applied. The amounts of sterol leached out of stratum corneum sheet when the sheet was immersed in aqueous solutions of Nal, NaBr, or NaSCN were much more than that of stratum corneum immersed in aqueous solutions of the other inorganic anions. The FTIR/ATR spectroscopy showed that the peaks at 2853 cm^?1 and 2924 cm^?1 in the IR absorption spectrum of the stratum corneum sheet of the mouse were shifted to higher frequencies by the anions which enhanced the transdermal drug permeation, while not shifted by the anions which did not have any permeation-enhancing activities or have permeation-reducing activities. These results suggest that sodium salts of some anions such as iodide, bromide and thiocyanate enhance transdermal permeation of salicylic acid through swelling and perturbation of the skin structure by these anions.     

Identifying potential indicators of the quality of end-of-life cancer care from administrative data.

PURPOSE: To explore potential indicators of the quality of end-of-life services for cancer patients that could be monitored using existing administrative data. METHODS: Quality indicators were identified and assessed by literature review for proposed indicators, focus groups with cancer patients and family members to assess candidate indicators and generate new ideas, and an expert panel ranking the meaningfulness and importance of each potential indicator using a modified Delphi approach. RESULTS: There were three major concepts of poor quality of end-of-life cancer care that could be examined using currently-available administrative data (such as Medicare claims): institution of new anticancer therapies or continuation of ongoing treatments very near death; a high number of emergency room visits, inpatient hospital admissions, or intensive care unit days near the end of life; and a high proportion of patients never enrolled in hospice, only admitted in the last few days of life, or dying in an acute-care setting. Concepts such as access to psychosocial and other multidisciplinary services and pain and symptom control are important and may eventually be feasible, but they cannot currently be applied in most data systems. Indicators based on limiting the use of treatments with low probability of benefit or indicators based on economic efficiency were not acceptable to patients, family members, or physicians. CONCLUSION: Several promising claims-based quality indicators were identified that, if found to be valid and reliable within data systems, could be useful in identifying health-care systems in need of improving end-of-life services.     

Performance measurement of the microPET focus 120 scanner.

The microPET Focus 120 scanner is a third-generation animal PET scanner dedicated to rodent imaging. Here, we report the results of scanner performance testing. METHODS: A (68)Ge point source was used to measure energy resolution, which was determined for each crystal and averaged. Spatial resolution was measured using a (22)Na point source with a nominal size of 0.25 mm at the system center and various off-center positions. Absolute sensitivity without attenuation was determined by extrapolating the data measured using an (18)F line source and multiple layers of absorbers. Scatter fraction and counting rate performance were measured using 2 different cylindric phantoms simulating rat and mouse bodies. Sensitivity, scatter fraction, and noise equivalent counting rate (NECR) experiments were repeated under 4 different conditions (energy window, 250 approximately 750 keV or 350 approximately 650 keV; coincidence window, 6 or 10 ns). A performance phantom with hot-rod inserts of various sizes was scanned, and several animal studies were also performed. RESULTS: Energy resolution at a 511-keV photopeak was 18.3% on average. Radial, tangential, and axial resolution of images reconstructed with the Fourier rebinning (FORE) and filtered backprojection (FBP) algorithms were 1.18 (radial), 1.13 (tangential), and 1.45 mm full width at half maximum (FWHM) (axial) at center and 2.35 (radial), 1.66 (tangential), and 2.00 mm FWHM (axial) at a radial offset of 2 cm. Absolute sensitivities at transaxial and axial centers were 7.0% (250 approximately 750 keV, 10 ns), 6.7% (250 approximately 750 keV, 6 ns), 4.0% (350 approximately 650 keV, 10 ns), and 3.8% (350 approximately 650 keV, 6 ns). Scatter fractions were 15.9% (mouse phantom) and 35.0% (rat phantom) for 250 approximately 750 keV and 6 ns. Peak NECR was 869 kcps at 3,242 kBq/mL (mouse phantom) and 228 kcps at 290 kBq/mL (rat phantom) at 250 approximately 750 keV and 6 ns. Hot-rod inserts of 1.6-mm diameter were clearly identified, and animal studies illustrated the feasibility of this system for studies of whole rodents and mid-sized animal brains. CONCLUSION: The results of this independent field test showed the improved physical characteristics of the F120 scanner over the previous microPET series systems. This system will be useful for imaging studies on small rodents and brains of larger animals.     

Saccular Aneurysm of the Azygos Anterior Cerebral Artery: Three Case Reports

The azygos anterior cerebral artery, a rare anomaly in the circle of Willis in which only a single vessel supplies the medial aspects of both anterior cerebral hemispheres, is closely associated with saccular aneurysms. We present three cases of azygos anterior cerebral artery aneurysms among the 781 cerebral aneurysms surgically treated at our institution in an 11-year period. These three cases all involved elderly women who presented with subarachnoid hemorrhage. Conventional cerebral angiography and CT angiography revealed small saccular aneurysms at the distal ends of the azygos anterior cerebral arteries. These aneurysms were clipped successfully using a bifrontal interhemispheric approach. Hence, the pathogenesis of these particular aneurysms relating to hemodynamic change, associated anomalies, and surgical pitfalls is discussed with review of literature.     

Successful outcome with extended allograft ischemic time in pediatric heart transplantation.

BACKGROUND: Many cardiac transplant programs have liberalized donor eligibility criteria in an attempt to maximize donor supply and to accommodate increasing demand. Although many studies have evaluated the potential adverse effects of prolonged donor ischemic time (DIT) in adults undergoing cardiac transplantation, relatively few have focused specifically on pediatric recipients that include a substantial number of patients and long-term follow-up. The focus of this study was to examine the effect of extended DIT on mortality after pediatric heart transplantation. METHODS: We conducted a retrospective review of our pediatric cardiac transplant experience in the past 11 years, comparing patients who received allografts and had ischemic times >240 minutes with those who had ischemic times <240 minutes. RESULTS: A total of 129 pediatric patients (<19 years) underwent orthotopic heart transplantation, of whom 78 (60.5%) had DIT <240 minutes and 51 (39.5%) had DIT >240 minutes. We found no statistically significant difference in age, sex, race, height, weight, or donor age between the groups (p = not significant). Post-transplant survival at 1, 5, and 10 years was similar for both groups: 91.2%, 88.0%, and 85.2%, respectively, for patients with DIT <240 minutes vs 89.6%, 87.2%, and 79.8%, respectively, for patients with DIT >240 minutes (p = 0.433). Additionally, using Cox proportional hazard models, extended DIT >240 minutes was not a statistically significant independent predictor of post-transplant mortality (odds ratio, 0.655; 95% confidence interval, 0.518-0.972; p = 0.684; standard error = 0.468). CONCLUSION: Procurement of hearts from distant locations with associated extended DIT is justified in the setting of increased demand and a fixed donor population.     

Treatment of congenital cystic adenomatoid malformation-does resection in the early postnatal period increase surgical risk?

OBJECTIVE: The recent development of fetal ultrasonography has allowed for an increasing number of prenatal diagnoses for congenital cystic adenomatoid malformation (CCAM). However, the appropriate surgical timing of these patients has not been studied as of yet. The aim of this study is to suggest a safe strategy for the treatment of CCAM by identifying the relationship between the timing of surgery and postoperative outcome. METHODS: Between 1987 and 2003, 40 patients (28 males, 12 females) underwent surgical resection for CCAM. The mean age was 38.6+/-9.1 (2 days-13 years) months. CCAM was diagnosed by prenatal ultrasonography in eight patients. Early operations were performed in four out of the eight. Operation was deferred until 2-12 months of age for the remaining four patients. RESULTS: Type I CCAM was found in 20 patients, type II in 20 and no patient exhibited type III. Five patients had associated pectus excavatum anomaly. There were no cases of operative mortality. Seventeen minor postoperative complications developed in 16 patients (40.0%): prolonged chest tube drain in 10, wound infection in 4, and 1 case of pneumonia, empyema and pleural space, respectively. The average hospital stay was 11.8 (6-29) days. During the mean follow-up period of 67.5 months, one patient died of accidental aspiration 7 months after operation during the postoperative recovery course of Ravich operation for pectus excavatum. The remaining patients reported doing well with normal physical activity. All five patients who underwent surgery at the age of under 1 month did not exhibit increased postoperative morbidity. CONCLUSIONS: We concluded that surgery for CCAM could be safely performed in all age groups with satisfactory long-term outcomes. It is suggested that early elective surgical correction can be recommended for a patient whose diagnosis was made in utero.     

Mapping the rat somatosensory pathway from the anterior cruciate ligament nerve endings to the cerebrum

The anterior cruciate ligament (ACL) serves as the primary restraint to anterior tibial translation. In addition to this biomechanical function, the ACL appears to have a function in neuromuscular control. This hypothesis was formulated after the discovery of mechanoreceptors within the ACL. The full somatosensory pathway from the ACL to the cerebrum has yet to be elucidated. In order to map this sensory pathway, we conducted a viral trans-synaptic tracing experiment using the neurotropic pseudorabies virus (PRV). The pseudorabies virus was injected into the ACL of rats and allowed to replicate and spread trans-synaptically for 6-7 days. The brain and spinal cord of each sacrificed rat was then removed and processed immunohistochemically to detect the presence of PRV. PRV-immunoreactive neurons were found to be localized in several different regions from the spinal cord to the cerebrum. Four nuclei in the reticular formation of the brain stem demonstrated strong positive labeling: the mesencephalic reticular nucleus, magnocellular reticular nucleus, paragigantocellular reticular nucleus, and gigantocellular reticular nucleus. This finding suggests that the nerve endings of the rat ACL project into the cerebrum and that the reticular formation may play an important role in the afferent pathway of those nerve endings.     

Centralisation of a hypospadias repair service--the Warwickshire experience.

An audit of the hypospadias repair service provided in the county of Warwickshire has shown that centralising all referrals to a single surgeon who uses limited, well-practiced techniques, greatly improves outcome. Comparison to previous audit of the service, when provided by a number of surgeons in the region, shows complication rates dropping - fistulae occurrence reducing from 35.8% to 6.7% and urethral stricture rates showing similar improvement from 4.4% to 0%. Overall productivity increased, and referral out of region dropped from 13% to 0%. This provides definitive evidence that restructuring of a service already in place has decreased morbidity and increased efficiency to give results comparable to published data.