Acute and chronic effects of bilateral lung transplantation without cardiopulmonary bypass on the first transplanted lung

BACKGROUND: Bilateral lung transplantation (BLT) without cardiopulmonary bypass (CPB) may exacerbate reperfusion injury to the initially engrafted lung because of increases in pulmonary flow during implantation of the second graft. METHODS: In a retrospective review of 23 BLT patients, we hypothesized that BLT without CPB injures the first transplanted lung measured by acute and late graft dysfunction compared to the second transplanted lung. Of the 23 BLT, 19 underwent transplantation without CPB while 4 patients were placed on CPB secondary to hemodynamic instability. RESULTS: Acute graft function was assessed by radiographic scoring of lung quadrants (blinded radiologist; 0 = no infiltrate; 1 = infiltrate; maximum = 2 per lung) and by arterial/alveolar oxygen tension ratios (PaO2/ FiO2) ratios. Late graft function was evaluated by quantitative perfusion scan. Lung perfusion was graded as abnormal if less than 50% on the right or less than 45% on the left (Fisher's exact). Radiographic scores were not different between first and second implanted lungs at 1 and 24 hours, PaO2/FiO2 ratios at 1 and 24 hours were 273+/-26 and 312+/-23, respectively, and perfusion scans at 3 and 12 months revealed normal differential blood flow. CONCLUSIONS: These findings suggest no acute or chronic differences occur between the first or second transplanted lung completed without CPB.     

The effects of state intergovernmental transfers on local public mental health services

The provision of public mental health services is shifting increasingly from states to local areas. Yet state governments continue to bear financial responsibility for the majority of these services. One implication of this trend is that the success of state policies become dependent on a state's ability to influence the behavior of local areas. This paper discusses the different options states have in designing intergovernmental grant contracts with local areas, and describes likely impacts of the different strategies. These propositions are then tested using data from the Ohio state mental health system from 1989-1993. This study finds that the design of grants affects public expenditures, local revenue generation, and the mix of services provided at the local level.     

Heart transplantation in children and young adults: early and intermediate-term results

The purpose of this article is to report our short- and intermediate-term follow-up of cardiac transplantation for congenital heart disease and cardiomyopathy in children (age greater than 6 months), adolescents, and young adults. Thirty patients (ages 8 months to 24 years) with end-stage heart failure have undergone cardiac transplantation in our program: 12 (40%) for postoperative end-stage heart failure, 9 (30%) as primary treatment for congenital heart disease, 5 (17%) for dilated cardiomyopathy, and 4 (13%) for restrictive/hypertrophic cardiomyopathy. Nineteen patients (63%) had undergone prior operations; 4 patients received transplants for failed Fontan procedures. Induction therapy with antithymocyte therapy was used routinely, and long-term immunosuppression was by cyclosporine and azathioprine alone. Rejection surveillance/diagnosis was based on echocardiographic criteria. Posttransplantation follow-up ranges from 3 to 78 months. Operative mortality was 3.3% (1/30). No patients have been diagnosed with either accelerated allograft atherosclerosis or posttransplantation lymphoproliferative disease. We conclude that cardiac transplantation may be performed with excellent early and intermediate-term results.     

Hyaluronan and chondroitin sulfate proteoglycans are colocalized to the ciliary zonule of the rat eye: a histochemical and immunocytochemical study

In previous studies, chondroitin sulfate proteoglycans have been localized to the periphery of the zonular fibers and the individual zonular fibrils (or microfibrils) after Cuprolinic blue staining in conjunction with chondroitinase digestions and immunogold labelling with 2-B-6 antibody. In the present study, we wished to determine if these proteoglycans are linked to hyaluronan to form a large multimolecular aggregate. To accomplish this, we localized the hyaluronan using a biotinylated hyaluronan-binding protein fragment of chondroitin sulfate proteoglycan, containing also the link protein, purified from bovine nasal cartilage. The results showed that the ciliary zonule of the rat eye was reactive with the biotinylated hyaluronan-binding probe as demonstrated by streptavidin-peroxidase-diaminobenzidine staining and streptavidin-gold labelling. Hyaluronan-gold labelling showed that the gold particles were mostly localized on the periphery of the zonular fibers, which was similar to the localization pattern of the zonule associated-proteoglycans. This hyaluronan-binding probe also strongly labelled the sites of zonule insertion over the basement membrane of the inner ciliary epithelium at the pars plana and the lens capsule at the equatorial region, which suggests its probable role in the attachment of ciliary zonule to the basement membranes. To demonstrate whether these two molecules are linked to one another, ultrastructural colocalization of both hyaluronan and chondroitin sulfate proteoglycans was performed on the same sections by double-gold labelling, and combined Cuprolinic blue staining and hyaluronan-gold labelling. Gold particles of 15 and 10 nm in sizes labelling both hyaluronan and chondroitin 4-sulfate, were colocalized to the surface of the zonular fibers. The combined Cuprolinic blue staining and hyaluronan-gold labelling showed that the gold particles were localized towards the ends of the Cuprolinic blue-stained rodlets, which strongly suggests that these chondroitin sulfate proteoglycans are linked to the hyaluronan chain to form a large aggregate surrounding the periphery of the zonular fibers. These ciliary zonule-associated proteoglycan-hyaluronan aggregates may play a role in organizing the individual zonular fibrils (microfibrils) into bundles of zonular fibers.     

Postprandial insulin profiles with implantable pump therapy may explain decreased frequency of severe hypoglycemia, compared with intensive subcutaneous regimens, in insulin-dependent diabetes mellitus patients

PURPOSE: To examine the mechanism of the decreased frequency of severe hypoglycemia with implantable pump therapy compared with subcutaneous intensive therapy. PATIENTS AND METHODS: Eight subjects with insulin-dependent diabetes mellitus (IDDM), enrolled in an implantable insulin pump study, were admitted to the General Clinical Research Center and on 2 separate days were given either a dose of preprandial insulin chosen to maintain normoglycemia for a standard (450 kcal, 50% carbohydrate) breakfast or 1.75 times the dose. The two doses were administered subcutaneously (by syringe or with an external pump) during one inpatient admission and by implantable pump (intraperitoneally, n=6; or intravenously, n=2) during a separate admission. Blood glucose, plasma-free insulin, and neurocognitive function were measured for 4 hours after the meal. RESULTS: Subcutaneous administration resulted in 7 episodes of hypoglycemia (2 with the usual dose and 5 with the 1.75-fold dose), defined as blood glucose less than 50 mg/dL; implantable pump treatment resulted in only 2 episodes, both with the 1.75-fold dose (P <0.05, Fisher's two-tailed test for implantable versus subcutaneous). Compared with subcutaneous delivery, implantable pump therapy provided significantly lower insulin levels during the final 2 hours after administration of the usual dose and the 1.75-fold dose (P <0.005). In addition to the decreased frequency of hypoglycemia, implantable pump therapy resulted in significantly lower area under the glycemia curve during the first 120 minutes with the 1.75-fold dose compared with subcutaneous administration. CONCLUSIONS: The lower frequency of severe hypoglycemia with intensive therapy administered by implantable pump therapy is explained by the more rapid clearance of insulin delivered intraperitoneally or intravenously compared with intensive subcutaneous injection regimens. The lower frequency of severe hypoglycemia with implantable pump therapy compared with subcutaneous therapy demonstrated in clinical trials is confirmed by this study, in which we attempted to induce hypoglycemia.     

Coordinated strategies for controlling micronutrient malnutrition: a technical workshop

Participants in a November 1991 workshop concluded that coordinated strategies for controlling malnutrition due to iodine, iron, vitamin A and other micronutrients deficiencies are technically feasible and should be given consideration in planning control efforts. Coordinated surveys involving clinical, biochemical and dietary assessment of multiple micronutrients are feasible. Multiple fortification is also possible using such vehicles as salt, processed rice or sugar. Supplementation efforts can be integrated with existing health care programs. Food-based strategies are also effective. The best examples have been community-based and have included a strong nutrition and health education component designed to change food consumption patterns, improve food preservation and preparation practices, and link income-generating activities with food production activities. Successful coordinated efforts will require a strong political commitment and a supportive infrastructure. Specific recommendations include the formation of national coordinating bodies for micronutrient deficiency control, establishment of a micronutrient information network and expansion of technical exchange and training.