Publications

OBJECTIVE

There is widespread debate over whether health plans should require enrollees to use "gatekeepers," which are primary care providers that coordinate care and control access to specialists. However, little is known about whether health plan gatekeeper requirements improve or reduce quality-of-care. Our objective was to examine whether gatekeeper requirements are associated with the utilization of cancer screening for breast, cervical, and prostate cancer.

DATA SOURCES

Three linked sources (N = 13,534): (1) 1996 Medical Expenditure Panel Survey (MEPS) Household Survey, a nationally representative, ongoing survey sponsored by the Agency for Healthcare Research and Quality; (2) 1996 MEPS Health Insurance Plan Abstraction, which codes data from health plan booklets obtained from privately insured respondents, and (3) 1995 National Health Interview Survey.

STUDY DESIGN/DATA COLLECTION

Cross-sectional, multivariate logistic regression analysis using secondary data.

PRINCIPAL FINDINGS

We found in multivariate analyses that women in gatekeeper plans were significantly more likely to obtain mammography screening (Odds Ratio [OR] = 1.22, 95 percent Confidence Interval [CI] 1.07-1.40), clinical breast examinations (OR = 1.39, 95 percent CI 1.23-1.57), and Pap smears (OR = 1.33, 95 percent CI 1.16-1.52) than women not in gatekeeper plans. In contrast, gatekeeper requirements were not associated with prostate cancer screening (OR = 1.11, 95 percent CI 0.93-1.33). We found no association between screening utilization and aggregate plan types (HMO, POS, PPO, FFS).

CONCLUSIONS

Gatekeeper requirements are associated with higher utilization of widely recommended cancer screening procedures, but not with utilization of a less uniformly recommended cancer screening procedure. Researchers should consider the analysis of specific plan characteristics rather than aggregate plan types in conducting future research, and insurers and policymakers should consider the potential benefits of gatekeepers with respect to preventive care when designing health plans and legislation.

Nitric oxide generation from porcine kidney slices is assessed using a new planar NO-selective amperometric sensor. The planar shape of the sensor allows for direct NO measurements near the surface (10 microm) of renal tissue slices in real time. Renal NO production may be modulated by the addition of L-arginine, arginine homopolymers (R2, R6, R10), and protamine, all of which can potentially transport across cellular membranes and provide a substrate for nitric oxide synthase within kidney parenchyma. Real-time amperometric measurements demonstrate that most L-arginine species can translocate across the cell membrane and rapidly increase NO production. However, no increase in NO generation is observed when the dimer of L-arginine (R2) is added to the solution bathing the tissue, suggesting that this species cannot permeate cell membranes. The degree of enhancement in NO generation observed for L-arginine and the larger peptides depends on the structure and follows the following sequence: R10 (decamer) > protamine > R6 (hexamer) > L-arginine. Protamine and the R10 decamer, especially, induce the largest increases in NO generation owing to their apparent rapid translocation into cells and subsequent cleavage by proteases to create high intracellular levels of L-arginine. The effect of sensor size (for sensor dimensions of 0.15- and 1-mm outer diameters) on the measured surface NO levels is also examined. The larger sensor traps more NO but hinders access of the L-arginine species to the tissue area between the flat distal plane of the sensor and the surface of the kidney slice. The use of such NO-generating peptides may be important in numerous biological systems that depend on NO production, such as ischemia-reperfusion injury and thrombogenesis.

The binding of bacteria and platelets may play a central role in the pathogenesis of infective endocarditis. Platelet binding by Streptococcus gordonii strain M99 is predominantly mediated by the 286-kDa cell wall-anchored protein GspB. This unusually large protein lacks a typical amino-terminal signal peptide and is translocated from the cytoplasm via a dedicated transport system. A 14-kb segment just downstream of gspB encodes SecA2 and SecY2, two components of the GspB-specific transport system. The downstream segment also encodes several putative glycosyl transferases that may be responsible for the posttranslational modification of GspB. In this study, we compared the abilities of M99 and two GspB(-) mutant strains to bind various lectins. GspB was found to have affinity for lectins that bind N-acetylglucosamine. We also examined variant forms of GspB that lack a carboxy-terminal cell wall-anchoring domain and thus are free of covalent linkage to cell wall peptidoglycan. Like native GspB, these truncated proteins appear to be heavily glycosylated, as evidenced by migration during sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent molecular mass >100 kDa in excess of the predicted mass, negligible staining with conventional protein stains, and reactivity with hydrazide following periodate oxidation. Furthermore, analysis of the carbohydrate associated with the GspB variants by high-pH anion-exchange chromatography revealed the presence of approximately 70 to 100 monosaccharide residues per GspB polypeptide (primarily N-acetylglucosamine and glucose). Analysis of GspB in protoplasts of secA2 or secY2 mutant strains, which do not export GspB, indicates that GspB is glycosylated in the cytoplasm of these strains. The combined data suggest that the native GspB is a glycoprotein and that it may be glycosylated prior to export.

PURPOSE OF REVIEW

The prevalence of lipodystrophy in HIV infection reported in the early literature has varied widely due in part to the different methods used in assessing and defining lipodystrophy in studies. There remains a lack of clarity regarding whether the peripheral lipoatrophy and central lipohypertrophy initially described in HIV infection are a result of separate mechanisms or a single mechanism. We review the current methods used to assess and define lipodystrophy in HIV infection; the prevalence and incidence of lipodystrophy reported in the recent HIV literature; and future directions in elucidating the morphologic changes associated with HIV infection.

RECENT FINDINGS

Different methods of assessing and defining lipodystrophy continue to lead to varying prevalence and incidence rates in recent large cross-sectional and prospective studies. Recent studies that include a predominantly HIV-uninfected comparison group and utilize bi-directional surveys to describe fat loss and fat gain in both peripheral and central body sites suggest that there is an HIV-associated lipoatrophy that affects both peripheral and central sites. In one study that used objective measures to quantify fat such as magnetic resonance imaging, HIV-associated subcutaneous lipoatrophy appeared to predominate when compared with a healthy control group.

SUMMARY

Peripheral and central lipoatrophy affecting subcutaneous fat is emerging as the dominant morphologic change associated with HIV infection when compared with those without known HIV infection. Studies of lipodystrophy in HIV infection should focus on lipoatrophy using direct measures of fat when possible.

BACKGROUND

As a component of the innate immune system, natural killer (NK) cells may play a significant role in the early events after solid-organ transplantation. Activated NK cells have been shown to infiltrate allografts in transplant models. To better understand NK cells and the role of NK cell receptors in transplantation, we have cloned and begun characterizing a novel rat molecule, rNKp30.

METHODS

RNKp30 cDNA was cloned by 5' rapid amplification of cDNA ends polymerase chain reaction (PCR) and reverse transcriptase (RT)-PCR from mononuclear cells infiltrating a rejecting liver allograft. Southern blot analysis was used to determine the rNKp30 gene copy number. RT-PCR and Northern blotting were used to examine rNKp30 RNA expression in NK cells, multiple tissues, and liver grafts. Immunocytochemistry, immunoprecipitation, and Western blot analysis with two anti-rNKp30 polyclonal antibodies, CA680 and CA1071, were performed. Tunicamycin and endoglycosidase treatments determined the extent of rNKp30 glycosylation.

RESULTS

RNKp30 is homologous to human and macaque NKp30. It is a single copy gene with five identified single-nucleotide polymorphisms. RNKp30 is expressed by NK cells and is detectable as a single transcript by Northern blot in normal spleen, lymph node, and lung tissues. RNKp30 is a variably N-glycosylated cell surface molecule with a protein backbone of approximately 21 kDa. Elevated transcript expression of rNKp30 is detected in both rejected and spontaneously accepted liver allografts, but not in syngeneic or cyclosporine A-treated allografts.

CONCLUSIONS

RNKp30 is a glycosylated surface NK cell receptor with limited polymorphism. This putative activation receptor is expressed in liver allografts and may participate in the innate immune response after transplantation.