The effect of managed care on use of health care services: results from two contemporaneous household surveys

This paper estimates treatment effects of managed care plans on the utilization of health care services using data from two contemporaneous, nationally representative household surveys from the USA. The paper exploits recent advances in simulation-based econometrics to take the endogeneity of enrollment into managed care plans into account and identify the causal relationship between managed care enrollment and utilization. Overall, results from the two surveys are remarkably similar, lending credibility to their external validity and to the econometric model and estimation methods. There is significant evidence of self-selection into managed care plans. After accounting for selection, an individual enrolled in an health maintenance organization (HMO) plan has 2 more visits to a doctor and has 0.1 more visits to the emergency room per year than would the same individual enrolled in a nonmanaged care plan.     

Monocrotaline pyrrole-induced megalocytosis of lung and breast epithelial cells: Disruption of plasma membrane and Golgi dynamics and an enhanced unfolded protein response

The pyrrolizidine alkaloid monocrotaline (MCT) initiates pulmonary hypertension by inducing a "megalocytosis" phenotype in target pulmonary arterial endothelial, smooth muscle and Type II alveolar epithelial cells. In cultured endothelial cells, a single exposure to the pyrrolic derivative of monocrotaline (MCTP) results in large cells with enlarged endoplasmic reticulum (ER) and Golgi and increased vacuoles. However, these cells fail to enter mitosis. Largely based upon data from endothelial cells, we proposed earlier that a disruption of the trafficking and mitosis-sensor functions of the Golgi (the "Golgi blockade" hypothesis) may represent the subcellular mechanism leading to MCTP-induced megalocytosis. In the present study, we investigated the applicability of the Golgi blockade hypothesis to epithelial cells. MCTP induced marked megalocytosis in cultures of lung A549 and breast MCF-7 cells. This was associated with a change in the distribution of the cis-Golgi scaffolding protein GM130 from a discrete juxtanuclear localization to a circumnuclear distribution consistent with an anterograde block of GM130 trafficking to/through the Golgi. There was also a loss of plasma membrane caveolin-1 and E-cadherin, cortical actin together with a circumnuclear accumulation of clathrin heavy chain (CHC) and alpha-tubulin. Flotation analyses revealed losses/alterations in the association of caveolin-1, E-cadherin and CHC with raft microdomains. Moreover, megalocytosis was accompanied by an enhanced unfolded protein response (UPR) as evidenced by nuclear translocation of Ire1alpha and glucose regulated protein 58 (GRP58/ER-60/ERp57) and a circumnuclear accumulation of PERK kinase and protein disulfide isomerase (PDI). These data further support the hypothesis that an MCTP-induced Golgi blockade and enhanced UPR may represent the subcellular mechanism leading to enlargement of ER and Golgi and subsequent megalocytosis.     

Emerging strategies for lowering serum phosphorous in patients with end-stage renal disease

Hyperphosphataemia is a major problem in patients with chronic kidney disease as it has been associated with increased morbidity and mortality. Over the last four decades, different modalities have been applied to treat hyperphosphataemia with varying degrees of success. Unfortunately, treatment strategies have led to unforeseen complications. These have prompted the development of new classes of medications with potentially better efficacy and few short-term and long-term side effects. This article reviews the causes, mechanism and management of hyperphosphataemia.     

Microsporidial keratitis in India: 16S rRNA gene-based PCR assay for diagnosis and species identification of microsporidia in clinical samples

PURPOSE: To evaluate 16S rRNA-based polymerase chain reactions for the detection and species identification of the microsporidia that cause keratitis. METHODS: Of the 5892 cases of microbial keratitis seen between September 2002 and December 2005, 31 (0.5%) microscopically diagnosed cases of microsporidial keratitis were included in the test group; 103 patients with nonmicrosporidial keratitis constituted the control group. A 16S rRNA-based pan-microsporidian PCR was chosen for the detection of microsporidian DNA. Species level identification was made using species-specific primer sets of Encephalitozoon spp (E. cuniculi, E. hellem, and E. intestinalis). Sequencing and BLAST analysis of amplicons obtained with pan-microsporidian primers were performed for validation. RESULTS: The corneal scrapings from 26 of 31 cases in the test group and 2 of 103 cases in the control group showed a 250- to 280-bp amplicon in PCR by pan-microsporidian primers (sensitivity of 83% and specificity of 98%). The amplicons of 13 of 26 test group samples were identified by species-specific PCR: E. cuniculi, n = 7 (549 bp); E. hellem; n = 3 (549 bp); E. intestinalis; n = 1 (520 bp). The two cases in the control group were identified to be E. cuniculi. The remaining 15 cases (test group) were confirmed to be Vittaforma corneae by sequencing and BLAST analysis. All species were confirmed by sequencing and database homology comparison. CONCLUSIONS: This study is the first to validate PCR-based assays for detection of microsporidial DNA in corneal scrapings. Pan microsporidian PCR can be a useful adjunct with smear examination in the diagnosis of microsporidial keratitis.     

Effects of respiration on the hemodynamics of hypertrophic obstructive cardiomyopathy

Marked respiratory variations in left ventricular outflow were noted in 8 of 9 patients with hypertrophie obstructive cardiomyopathy. Maximal systolic gradients were noted at the end of expiration, the smallest gradients at the end of inspiration. The reductions in left ventricular systolic pressures were accompanied by a rise in arterial systolic pressures and vice versa. These effects were not abolished by beta-adrenergic blockage and were exaggerated after “vensection.”

The Valsalva maneuver resulted in increased obstruction during the period of peak strain, and after release the obstruction was diminished during the overshoot period. These responses persisted after beta-adrenergic blockade.

The probable underlying mechanisms of varying obstruction observed with respiration and with the Valsalva maneuver are related to changes in volume of the left ventricle. The left ventricular outflow obstruction in hypertrophie obstructive cardiomyopathy is increased by a diminished ventricular volume, and relieved by an increased ventricular volume.     

Protein farnesyltransferase inhibitors exhibit potent antimalarial activity

New therapeutics to combat malaria are desperately needed. Here we show that the enzyme protein farnesyltransferase (PFT) from the malaria parasite Plasmodium falciparum (P. falciparum) is an ideal drug target. PFT inhibitors (PFTIs) are well tolerated in man, but are highly cytotoxic to P. falciparum. Because of their anticancer properties, PFTIs comprise a highly developed class of compounds. PFTIs are ideal for the rapid development of antimalarials, allowing "piggy-backing" on previously garnered information. Low nanomolar concentrations of tetrahydroquinoline (THQ)-based PFTIs inhibit P. falciparum PFT and are cytotoxic to cultured parasites. Biochemical studies suggest inhibition of parasite PFT as the mode of THQ cytotoxicity. Studies with malaria-infected mice show that THQ PFTIs dramatically reduce parasitemia and lead to parasite eradication in the majority of animals. These studies validate P. falciparum PFT as a target for the development of antimalarials and describe a potent new class of THQ PFTIs with antimalaria activity.     

Minimally invasive pulmonary artery banding: a new approach

BACKGROUND: A variety of approaches have been described for banding of the pulmonary artery. The indications for this procedure are limited; however in developing countries, many patients still need pulmonary artery banding for a variety of reasons. We describe a new approach, minimally invasive, using only a split in the manubrium sterni to conduct the procedure. METHODS AND RESULTS: Between January 2000 and May 2002, 19 patients who had undergone pulmonary artery banding using a minimally invasive technique were compared with 20 cases of pulmonary artery banding performed by the conventional technique. The mortality was similar in the two groups (p=0.45). The period of intubation and duration of intensive care unit stay were significantly shorter in the minimally invasive group (p=0.015 and 0.002, respectively). The duration of hospital stay was not significantly different between the 2 groups (p=0.139). In the minimally invasive group, three patients underwent subsequent reoperation. CONCLUSIONS: Minimally invasive pulmonary artery banding is useful in babies with high-flow cardiac lesions and cardiac cachexia.