Effect of imipramine on mood and enumerative measures of immune status in depressed patients with HIV illness

OBJECTIVE: The authors' first objective was to ascertain whether imipramine is superior to placebo in treating axis I depressive disorders in the context of HIV illness. Supplementary questions were whether severity of immunodeficiency is associated with antidepressant response and whether patients with greater immunodeficiency can tolerate standard doses of imipramine. Second, the authors sought to determine whether imipramine treatment is associated with changes in immune status. METHOD: A double-blind, randomized placebo-controlled trial of imipramine was conducted in a university-affiliated research outpatient clinic. After 6 weeks of treatment, responders were maintained double-blind for another 6 weeks and nonresponders were removed from the study and treated openly. All patients were offered 26 weeks of treatment. Of the 97 patients who were randomly assigned to placebo or imipramine, 80 completed the 6-week phase. Main outcome measures included the Clinical Global Impression, the Hamilton Depression Rating Scale, the Brief Symptom Inventory, and CD4 cell count. RESULTS: Among study completers, 31 (39%) had AIDS. The response rate to imipramine was 74% and the response rate to placebo was 26%. There was no difference in depression response between patients with more or less severe immunodeficiency, nor was there a difference in medication dose or side effects. Neither type nor duration of treatment influenced CD4 cell count during the course of treatment. CONCLUSIONS: Depressed patients with HIV illness respond to imipramine at the same rate as medically healthy depressed patients. Severity of immunosuppression is not associated with imipramine treatment outcome. There is no evidence that imipramine has negative effects on enumerative measures of immune status.     

Phase transformations in Au(Fe) nano- and microparticles obtained by solid state dewetting of thin Au–Fe bilayer films

Sub-micrometer-sized particles of Au–Fe alloys were obtained by solid-state dewetting of single-crystalline Au–Fe bilayer films, deposited on c-plane sapphire (α-Al₂O₃) substrates. Depending on the annealing parameters, precipitation of an Fe-rich phase occurred on the side facets of the particles in an interface-limited reaction. Based on the literature values of surface and interface energies in the system, the precipitates were expected to grow inside the Au(Fe) particles, resulting in an (Fe) core–(Au) shell morphology. However, more complex, time-dependent precipitate morphologies were observed, with faceted Fe-rich precipitates attached to the parent faceted Au-rich particles of the same height being dominant at the last stages of the transformation. Our high-resolution transmission electron microscopy observations revealed a nanometric segregation layer of Au on the surface of Fe-rich particles and at their interface with sapphire. This segregation layer modified the surface and interface energies of the Fe-rich particles. A thermodynamic transformation model based on the concept of weighted mean curvature was developed, describing the kinetics of precipitations and morphology evolution of the particles during the dewetting process. Employing the values of surface and interface energies modified by segregation resulted in a good qualitative agreement between theory and experiment.     

Particle rearrangement during sintering of heterogeneous powder mixtures: A combined experimental and theoretical study

We studied the morphology evolution of individual three-particle W-Cu-W agglomerates during sintering anneals at 1000 °C. The angle between the lines connecting the centers of W and Cu particles decreased during annealing, provided its initial value was different from 180°. While the W particles retained their spherical shape during sintering, the shape of Cu particles changed significantly after long sintering times. Both the rate of the particles’ rearrangement and the linear shrinkage of the particle pairs determined in the experiments increased with decreasing initial angle between the particles. We proposed an analytical model of sintering of cylindrical three-wire agglomerates controlled by self-diffusion of Cu atoms along the surface of Cu wire and along the W-Cu interphase boundary. The proposed model incorporates a thermodynamic method for calculating the distribution of chemical potential of metal atoms moving along the rigid cylindrical interphase boundary. The predictions of the model were in good agreement with the experimental data, underlying an important role played by capillary-driven diffusion in rearrangement of particles during sintering.     

Monoclonal origin of multicentric Kaposi's sarcoma lesions

BACKGROUND: Kaposi's sarcoma has features of both hyperplastic proliferation and neoplastic growth. Multiple lesions, in which spindle cells are prominent, often arise synchronously over widely dispersed areas. We tested the hypothesis that the spindle cells in these multicentric lesions originate from a single clone of precursor cells. METHODS: To determine whether Kaposi's sarcoma is a monoclonal disorder, we assessed the methylation patterns of the androgen-receptor gene (HUMARA) in multiple lesions from women with the acquired immunodeficiency syndrome. In polyclonal tissues, about half the copies of each HUMARA allele are methylated, whereas in cells derived from a single clone all the copies of only one allele are methylated. To minimize contamination by normal DNA, we used microdissection to isolate areas composed primarily of spindle cells, the putative tumor cells. RESULTS: Eight patients with a total of 32 tumors were studied. Of these tumors, 28 had highly unbalanced methylation patterns (i.e., predominant methylation of one HUMARA allele). In all the tumors that had unbalanced methylation from a given patient, the same allele predominated. CONCLUSIONS: These data indicate that Kaposi's sarcoma is a disseminated monoclonal cancer and that the changes that permit the clonal outgrowth of spindle cells occur before the disease spreads.     

The effect of zidovudine on neuropsychiatric measures in HIV-infected men

The production of interleukin-1 (IL-1) by rabbit Peyer's patch M cells populating the follicle-associated epithelium (FAE) was studied. Sorted 5D9+ phagocytic epithelial M cells synthesized IL-1 after stimulation with lipopolysaccharide (LPS) in vitro, as evidenced by the ability of culture supernatants to induce the proliferation of the T-cell line D10.G4.1. Fixed LPS-stimulated M cells were less effective at mediating T-cell proliferation than supernatants from LPS-activated M cells. The magnitude of T-cell proliferation was M-cell concentration dependent, and proportional to the dose of LPS. The M-cell-mediated D10.G4.1 cell proliferation was inhibited > 75% with anti-IL-1 alpha, but < 50% with similar concentrations of anti-IL-1 beta. The results show that M cells secrete IL-1, and suggest the participation of M cells in the delivery of a localized co-stimulatory signal for T-cell and B-cell proliferation in the microenvironment of gut-associated lymphoid tissue (GALT).     

Factors associated with implementation of preventive care measures in patients with diabetes mellitus

BACKGROUND: There is only limited information on the extent to which physicians' characteristics affect the level of care and implementation of guidelines in patients with diabetes mellitus. OBJECTIVE: To identify physician characteristics associated with implementation of measures for preventive care in patients with diabetes mellitus and the distribution of implementation of these measures among them. PATIENTS AND METHODS: A retrospective chart audit of 519 patients eligible for health maintenance organization insurance on December 31, 1994, representing patients with diabetes receiving care from 22 primary care physician-providers of a managed care medical group in suburban North Los Angeles, Calif, and seen by physicians between January 1993 and December 1994. A short retroactive questionnaire for participating physicians was also used. The outcome measures were (1) measurement of serum high-density lipoprotein cholesterol; (2) urinalysis for the detection of proteinuria; and (3) ophthalmology referral for dilated fundus examination. RESULTS: Over a period of 2 years 78% of the patients had a high-density lipoprotein cholesterol determination, 80% had a test for proteinuria, and 62% were referred to an ophthalmologist. After adjustment for patient pool differences, physicians who were perceived by the administration of the medical group as "fast," based on a blinded evaluation of their number of patient encounters per unit time, had an odds ratio of 0.60 (95% confidence interval [CI], 0.37-0.95; P=.03) to obtain a high-density lipoprotein cholesterol determination in their patients and an odds ratio of 0.53 (95% CI, 0.32-0.87; P=.01) to test their patients for proteinuria. In patients requiring insulin, of fast physicians, the odds ratio for a referral for ophthalmology screening was 0.25 (95% CI, 0.07-0.85; P= .03). Duration of time in practice of over 15 years and disagreement with practice guidelines were associated with better outcomes. There was no association between physician sex, internal medicine training, or number of patients with diabetes in the practice and the implementation of outcomes. There was a highly significant association between the implementation of an outcome and the implementation of the other 2, resulting in a nonhomogeneous distribution of health care delivery. Physicians' estimate of their rate of implementation of outcomes, as assessed by the questionnaires, overestimated their actual performance while being in proportion with the documented rates. Most physicians took responsibility for the nonimplementation, accepting that it was an oversight on their part as opposed to an encounter with patient resistance. CONCLUSIONS: Most physicians believe that the lack of implementation of the measures for preventive care in patients with diabetes mellitus is an oversight. The oversight is more prevalent in the practices of busy physicians. The result is a nonhomogeneous distribution of health care. Computer reminders might be the solution.     

Evaluation of peak picking quality in LC-MS metabolomics data

The output of LC-MS metabolomics experiments consists of mass-peak intensities identified through a peak-picking/alignment procedure. Besides imperfections in biological samples and instrumentation, data accuracy is highly dependent on the applied algorithms and their parameters. Consequently, quality control (QC) is essential for further data analysis. Here, we present a QC approach that is based on discrepancies between replicate samples. First, the quantile normalization of per-sample log-signal distributions is applied to each group of biologically homogeneous samples. Next, the overall quality of each replicate group is characterized by the Z-transformed correlation coefficients between samples. This general QC allows a tuning of the procedure's parameters which minimizes the inter-replicate discrepancies in the generated output. Subsequently, an in-depth QC measure detects local neighborhoods on a template of aligned chromatograms that are enriched by divergences between intensity profiles of replicate samples. These neighborhoods are determined through a segmentation algorithm. The retention time (RT)-m/z positions of the neighborhoods with local divergences are indicative of either: incorrect alignment of chromatographic features, technical problems in the chromatograms, or to a true biological discrepancy between replicates for particular metabolites. We expect this method to aid in the accurate analysis of metabolomics data and in the development of new peak-picking/alignment procedures.