Clinical Impact of Community-Acquired Respiratory Viruses on Bronchiolitis Obliterans After Lung Transplant

Community-acquired viral respiratory tract infections (RTI) in lung transplant recipients may have a high rate of progression to pneumonia and can be a trigger for immunologically mediated detrimental effects on lung function. A cohort of 100 patients was enrolled from 2001 to 2003 in which 50 patients had clinically diagnosed viral RTI and 50 were asymptomatic. All patients had nasopharyngeal and throat swabs taken for respiratory virus antigen detection, culture and RT-PCR. All patients had pulmonary function tests at regular intervals for 12 months. Rates of rejection, decline in forced expiratory volume (L) in 1 s (FEV-1) and bacterial and fungal superinfection were compared at the 3-month primary endpoint. In the 50 patients with RTI, a microbial etiology was identified in 33 of 50 (66%) and included rhinovirus (9), coronavirus (8), RSV (6), influenza A (5), parainfluenza (4) and human metapneumovirus (1). During the 3-month primary endpoint, 8 of 50 (16%) RTI patients had acute rejection versus 0 of 50 non-RTI patients (p=0.006). The number of patients experiencing a 20% or more decline in FEV-1 by 3 months was 9 of 50 (18%) RTI versus 0 of 50 non-RTI (0%) (p=0.003). In six of these nine patients, the decline in FEV-1 was sustained over a 1-year period consistent with bronchiolitis obliterans syndrome (BOS). Community-acquired respiratory viruses may be associated with the development of acute rejection and BOS.     

Transmural and endocardial Purkinje activation in pigs before local myocardial activation after defibrillation shocks.

BACKGROUND: Earliest recorded postshock myocardial activations in pigs originate in the subepicardium of the apex and lateral free wall of the left ventricle (LV) 30-90 ms after the shock. OBJECTIVE: The purpose of this study was to determine whether the Purkinje system is a candidate for the source of postshock activations by performing endocardial and transmural postshock activation mapping. METHODS: In five pigs, 32 plunge needles with 12 electrodes (1-mm spacing) were inserted into the LV apex and lateral free wall. Up to 70 plunge needles with six electrodes (2-mm spacing) were spread throughout the remainder of the LV, while 9-12 plunge needles with four electrodes (2-mm spacing) were inserted into the right ventricle. A basket catheter with 32 bipolar recording sites was inserted into the LV. Defibrillation-threshold (DFT)-level shocks were delivered during 10 episodes of electrically induced ventricular fibrillation. Electrograms of postshock activation cycles were analyzed for Purkinje and myocardial activations. RESULTS: Purkinje activations were recorded before local myocardial activation in 9% of basket electrograms and in 15% of plunge needles during the first postshock activation cycle. Purkinje activations were identified during the first and subsequent several postshock activation cycles in at least one basket and one needle electrogram in 96% and 98% of defibrillation episodes, respectively. CONCLUSIONS: The Purkinje system is active during the early postshock activation cycles after DFT-level shocks. Further studies are required to determine whether activation initiates in the Purkinje system or whether it is activated by the myocardium or by Purkinje-myocardial junctional cells.     

Permanent access to the portal system for cellular transplantation using an implantable port device.

A novel application of the implantable Port-a-Cath (PAC) system is described in the context of cellular transplantation. A silicone catheter was inserted in a collateral branch of the portal vein and connected to a port device positioned subcutaneously on the left thoracic cage. This permanent vascular access allowed iterative intraportal infusions of allogenic hepatocytes without the need of repeated transhepatic catheterization of the portal vein. Using this technique, repeated infusions of cryopreserved and / or fresh hepatocytes were successfully carried out in 3 children with inborn errors of liver metabolism, with the aim of progressively providing a sufficient mass of transplanted liver cells to stabilize the metabolic condition of the patients. We suggest that this technique might also be valuable in pancreatic islet cell transplantation.     

Dietary selenium's protective effects against methylmercury toxicity

Dietary selenium (Se) status is inversely related to vulnerability to methylmercury (MeHg) toxicity. Mercury exposures that are uniformly neurotoxic and lethal among animals fed low dietary Se are far less serious among those with normal Se intakes and are without observable consequences in those fed Se-enriched diets. Although these effects have been known since 1967, they have only lately become well understood. Recent studies have shown that Se-enriched diets not only prevent MeHg toxicity, but can also rapidly reverse some of its most severe symptoms. It is now understood that MeHg is a highly specific, irreversible inhibitor of Se-dependent enzymes (selenoenzymes). Selenoenzymes are required to prevent and reverse oxidative damage throughout the body, particularly in the brain and neuroendocrine tissues. Inhibition of selenoenzyme activities in these vulnerable tissues appears to be the proximal cause of the pathological effects known to accompany MeHg toxicity. Because Hg's binding affinities for Se are up to a million times higher than for sulfur, its second-best binding partner, MeHg inexorably sequesters Se, directly impairing selenoenzyme activities and their synthesis. This may explain why studies of maternal populations exposed to foods that contain Hg in molar excess of Se, such as shark or pilot whale meats, have found adverse child outcomes, but studies of populations exposed to MeHg by eating Se-rich ocean fish observe improved child IQs instead of harm. However, since the Se contents of freshwater fish are dependent on local soil Se status, fish with high MeHg from regions with poor Se availability may be cause for concern. Further studies of these relationships are needed to assist regulatory agencies in protecting and improving child health.     

Scale-up of Adhesive Transdermal Drug Delivery Systems

Pharmaceutical Research -     

An approach to protein restriction in children with renal insufficiency

Children with mild to moderate renal insufficiency may be at an increased risk for developing glomerulosclerosis and subsequent renal failure. Low protein diets (LPD) have been shown to delay the progression of renal insufficiency in laboratory animals and may be of benefit in adult humans. The nutritional costs of a LPD in adults are reportedly minimal. We review the protein and caloric requirements of growing children and discuss the potential harmful effects and benefits of an LPD in this population. We also discuss dietary adherence and the difficulty of designing an LPD for children. We conclude that the protein content of a typical American diet can safely be reduced to, but not below, the recommended daily allowance for protein if diets are carefully planned, patients and their parents extensively counseled, and if dietary supplements are given to help meet the caloric and vitamin-mineral nutrient needs of growing children. In addition, ongoing nutritional assessment, counseling, and frequent monitoring of growth, diet and biochemical indicators of protein status are essential for maintaining the health of these children.     

Health-related behaviors in Korea: smoking, drinking, and perinatal care.

The prevalence of major health-related behaviors and the relationship of these factors with selected sociodemographic factors were studied in South Korea. Subjects studied were household heads and their wives from 989 households. Age-standardized prevalences of smoking were 74.8% and 2.9% for men and women respectively, with no urban-rural difference. There was a tendency of younger or less-educated men smoking more heavily. The prevalence of use of alcoholic drinks were 79.8% and 26.0% for men and women respectively. More drinking was associated with a younger age and higher level of education. The mean prevalences of prenatal care, clinic or hospital delivery, and breastfeeding were 75.0%, 62.6%, and 75.2% respectively in the urban area, whereas the corresponding rates were 63.0%, 50.9%, and 81.1% in the rural area. Higher rates in prenatal care and hospital delivery were associated with a younger age and higher educational level, while breastfeeding showed the opposite trend.     

Mammalian wound repair environment does not permit skeletal muscle regeneration

Repair and regeneration are mutually exclusive responses to injury. Previous studies have shown that wound fluids promote proliferation, but not differentiation, of myoblasts in vitro. This study explored the ability of the repair environment within polyvinyl alcohol sponges to support cellular events of skeletal muscle regeneration in vivo. Neonatal rat L8 myoblasts were modified to express beta-galactosidase then inoculated into plain sponges or sponges containing minced muscle. Labeled myoblasts were found in myotubes within minced muscle. In contrast, myoblasts inoculated into sponges lacking muscle remained mononucleate. Occurrence of labeled myoblasts within myotubes, which required fusion, represents differentiation of inoculated myoblasts to participate in regeneration. Failure of myoblasts to form myotubes in sponges lacking muscle suggests that this wound repair environment cannot support morphologic differentiation of myoblasts. Although this repair environment can support the survival of myoblasts, it did not support myogenesis, an event necessary to complete skeletal muscle regeneration. Data from this study reinforce earlier studies in vitro and suggest that the properties attributed to wound fluids are inherent in the wound environment. Whether the inability of this environment to support myogenesis is the consequence of the absence of essential factors or the presence of inhibitors remains to be determined.