Correlates of nonparticipation in an HIV prevention program for MSM.

Providing HIV prevention services to high-risk individuals remains challenging. We assessed factors associated with nonparticipation among high-risk, sexually active MSM found eligible to participate in a brief, telephone-delivered HIV prevention trial designed to evaluate the efficacy of motivational enhancement therapy (the Sex Check). Two levels of nonparticipation are evaluated: eligible participants who did versus those who did not complete their baseline/enrollment interview, and enrolled participants who did versus those who did not attend any of their counseling sessions. Nonenrollers were younger, less educated, more closeted, and were more likely to report sex with an injection drug using partner. Enrolled participants who did not engage in their counseling session(s) were less educated, reported greater use of alcohol and drugs during sex and use of injection drugs. Innovative methods to reduce barriers to engaging high-risk, sexually active MSM in risk reduction counseling are needed.     

Long-term effects of glaucoma therapy with 4% pilocarpine gel on corneal clarity and endothelial cell density

Corneal thickness measurements and endothelial cell counts were carried out in 34 patients undergoing treatment for glaucoma with 4% pilocarpine gel between 18 to 78 months after initiation of therapy. The corneal thickness and endothelial cell population were found to be within normal limits in all cases except two, one patient with increased corneal thickness who had recently undergone cataract and glaucoma filtering surgery and another patient with decreased cell count who had an old endothelial scar sustained prior to pilocarpine gel therapy. There was a very close correlation for both of these parameters noticed in patients treated with pilocarpine gel and in age-matched control group of patients with glaucoma. The present study has shown that there are no adverse corneal effects with pilocarpine gel therapy.     

The Effect of Health Plan Characteristics on Medicare+Choice Enrollment

Objective. To provide national estimates of the effect of out-of-pocket premiums and benefits on Medicare beneficiaries' choice among managed care health plans.
Data Sources/Study Setting. The data represent the population of all Medicare+Choice (M+C) plans offered to Medicare beneficiaries in the United States in 1999.
Study Design. The dependent variable is the log of the ratio of the market share of the j th health plan to the lowest cost plan in the beneficiary's county of residence. The explanatory variables are measures of premiums and benefits in the j th health plan relative to the premiums and benefits in the lowest cost plan.
Data Collection Methods. The data are from the 1999 Medicare Compare database, and M+C enrollment data from the Centers for Medicare and Medicaid Services (CMS).
Principal Findings. A $10 increase in an M+C plan's out-of-pocket premium, relative to its competitors, is associated with a decrease of four percentage points in the j th plan's market share (i.e., from 25 to 21 percent), holding the premiums of competing plans constant.
Conclusions. Although our price elasticity estimates are low, the market share losses associated with small changes in a health plan's premium, relative to its competitors, may be sufficient to discipline premiums in a competitive market. Bidding behavior by plans in the Medicare Competitive Pricing Demonstration supports this conclusion.     

Brain tissue microarrays in dementia research: White matter microvascular pathology in Alzheimer's disease

Tissue microarrays (TMA) consist of up to 1000 cylindrical tissue cores from different donor paraffin blocks relocated into one recipient block, allowing for efficient histopathological studies by fluorescence in situ hybridization, RNA in situ hybridization or immunohistochemistry. On the background of the increasing interest of the TMA technique in cancer research and the suggestion of its application also in studies of non‐neoplastic intracranial disorders, the technique was applied to pathologic white matter in AD brains. Eight cases with AD and concomitant white matter pathology were neuropathologically diagnosed on whole brain coronal slides. The TMA technique was used to grade severity of white matter pathology and to quantify small vessels with traditional staining and immunohistochemical markers. These measurements were compared with the whole brain neuropathological assessment. The technique produced good results with preserved tissue structures as confirmed by the whole brain evaluation. Severity of white matter pathology evaluated on the TMA cores correlated negatively with small vessel quantities, and statistically significant differences in vessel quantities paralleled different grades of white matter pathology. It is concluded that the TMA technique could be further utilized in studies of dementing disorders, and may have its advantages in large, clinically well‐characterized materials (e.g. in quantitative mapping of white matter changes).     

Pituitary responsiveness to GH-releasing hormone, GH-releasing peptide-2 and thyrotrophin-releasing hormone in critical illness

OBJECTIVE Protein hypercatabolism and preservation of fat depots are hallmarks of critical illness, which is associated with blunted pulsatile GH secretion and low circulating IGF-I, TSH, T4 and T3. Repetitive TRH administration is known to reactivate the pituitary-thyroid axis and to evoke paradoxical GH release in critical illness. We further explored the hypothalamic-pituitary function in critical illness by examining the effects of GH-releasing hormone (GHRH) and/or GH-releasing peptide-2 (GHRP-2) and TRH administration. PATIENTS AND DESIGN Critically ill adults (n=40; mean age 55 years) received two i.v. boluses with a 6-hour interval (0900 and 1500 h) within a cross-over design. Patients were randomized to receive consecutively placebo and GHRP-2 (n=10), GHRH and GHRP-2 (n=10), GHRP-2 and GHRH+GHRP-2 (n=10), GHRH+GHRP-2 and GHRH+GHRP-2+TRH (n=10). The GHRH and GHRP-2 doses were 1μg/kg and the TRH dose was 200μg. Blood samples were obtained before and 20, 40, 60 and 120 minutes after each injection. MEASUREMENTS Serum concentrations of GH, T4, T3, rT3, thyroid hormone binding globulin (TBG), IGF-I, insulin and cortisol were measured by RIA; PRL and TSH concentrations were determined by IRMA. RESULTS Critically ill patients presented a striking GH response to GHRP-2 (mean±SEM peak GH 51±9 μg/l in older patients and 102±2μg/l in younger patients; P=0.005 vs placebo). The mean GH response to GHRP-2 was more than fourfold higher than to GHRH (P=0.007). In turn, the mean GH response to GHRH+GHRP-2 was 2.5-fold higher than to GHRP-2 alone (P=0.01), indicating synergism. Adding TRH to the GHRH+GHRP-2 combination slightly blunted this mean response by 18% (P=0.01). GHRP-2 had no effect on serum TSH concentrations whereas both GHRH and GHRH+GHRP-2 evoked an increase in peak TSH levels of 53 and 32% respectively. The addition of TRH further increased this TSH response < ninefold (P=0.005), elicited a 60% rise in serum T3 (P=0.01) and an 18% increase in T4 (P=0.005) levels, without altering rT3 or TBG levels. GHRH and/or GHRP-2 induced a small increase in serum PRL levels. The addition of TRH magnified the PRL response 2.4-fold (P=0.007). GHRP-2 increased basal serum cortisol levels (531±29nmol/l) by 35% (P=0.02); GHRH provoked no additional response, but adding TRH further increased the cortisol response by 20% (P=0.05). CONCLUSIONS The specific character of hypothalamic-pituitary function in critical illness is herewith extended to the responsiveness to GHRH and/or GHRP-2 and TRH. The observation of striking bursts of GH secretion elicited by GHRP-2 and particularly by GHRH+GHRP-2 in patients with low spontaneous GH peaks opens the possibility of therapeutic perspectives for GH secretagogues in critical care medicine.     

Inhibition of Human Mammary Cell Line Proliferation by Membrane Lectin-Mediated Uptake of Ha-ras Antisense Oligodeoxynucleotide

The Ha-ras oncogene promotes cell proliferation. Antisense oligonucleotides complementary to the ras gene sequence encompassing a mutated codon 12 selectively induce a cell proliferation inhibition. However, the concentration required to reach an effective inhibition is high due to the low efficiency of the oligonucleotide crossing through cell membranes, leading to a low concentration in the cytosol and/or the nucleoplasm. In the present paper, we show that anti-ras oligonucleotides linked to a glycosylated carrier, serum albumin bearing mannose 6-phosphate residues, are more efficient than free oligonucleotides or oligonucleotides bound to an unglycosylated carrier at inhibiting proliferation of a human tumor mammary cell line expressing the mutated Ha-ras. Using fluorescein-labeled neoglycoproteins and fluorescein-labeled oligonucleotides bound to neoglycoproteins, flow cytometry and confocal microscopy revealed that (i) these tumor cells express a membrane lectin specific for mannose 6-phosphate-bearing proteins, (ii) the membrane lectin actively mediates the uptake of macromolecules substituted with mannose 6-phosphate, and (iii) the fluorescein-labeled oligonucleotides bound to the neoglycoprotein accumulate in intracellular vesicles. Furthermore, with antisense oligonucleotides carried by the neoglycoproteins, the concentration required to inhibit cell proliferation is lower than that of the carrier-free antisense oligonucleotides.