Is prior course of illness relevant to acute or longer-term outcomes in depressed out-patients? A STAR*D report.

BACKGROUND: Major depressive disorder (MDD) is commonly chronic and/or recurrent. We aimed to determine whether a chronic and/or recurrent course of MDD is associated with acute and longer-term MDD treatment outcomes. METHOD: This cohort study recruited out-patients aged 18-75 years with non-psychotic MDD from 18 primary and 23 psychiatric care clinics across the USA. Participants were grouped as: chronic (index episode >2 years) and recurrent (n = 398); chronic non-recurrent (n=257); non-chronic recurrent (n=1614); and non-chronic non-recurrent (n = 387). Acute treatment was up to 14 weeks of citalopram (≤ 60 mg/day) with up to 12 months of follow-up treatment. The primary outcomes for this report were remission [16-item Quick Inventory of Depressive Symptomatology - Self-Rated (QIDS-SR(16)) ≤ 5] or response (≥ 50% reduction from baseline in QIDS-SR(16)) and time to first relapse [first QIDS-SR16 by Interactive Voice Response (IVR) ≥ 11]. RESULTS: Most participants (85%) had a chronic and/or recurrent course; 15% had both. Chronic index episode was associated with greater sociodemographic disadvantage. Recurrent course was associated with earlier age of onset and greater family histories of depression and substance abuse. Remission rates were lowest and slowest for those with chronic index episodes. For participants in remission entering follow-up, relapse was most likely for the chronic and recurrent group, and least likely for the non-chronic, non-recurrent group. For participants not in remission when entering follow-up, prior course was unrelated to relapse. CONCLUSIONS: Recurrent MDD is the norm for out-patients, of whom 15% also have a chronic index episode. Chronic and recurrent course of MDD may be useful in predicting acute and long-term MDD treatment outcomes.

Monoclonal antibody PD41 recognizes an antigen restricted to prostate adenocarcinomas.

A monoclonal antibody (MAb) designated PD41 (IgG1k) was generated by hyperimmunizing BALB/c mice with a membrane preparation prepared from a moderately to poorly differentiated prostate carcinoma surgical specimen. The immunohistochemical reactivity of MAb PD41 was shown to be highly restricted to the ductal epithelia and secretions of prostate adenocarcinoma tissues. Sixty-five % of the prostate tumor specimens were stained with MAb PD41, whereas no staining of the fetal or benign prostate specimens was observed. PD41 reacted minimally with normal prostate tissues, with less than 1% of the epithelial cells staining. This MAb did not react with nonprostate carcinomas or to a variety of normal human tissues. Using both radioimmunoassay and immunofluorescent procedures, several cultured human tumor cell lines, human blood cells, and purified antigens to prostate-specific antigen and prostatic acid phosphatase also were found not to express the PD41 antigen. MAb PD41 also was shown to bind to the target antigen present in seminal plasma obtained from prostate carcinoma patients but not to seminal plasma from normal donors. Immunoblots of gel-separated components of prostate carcinoma tissue extracts indicate that the molecular weight of the proteins carrying the PD41 antigenic determinant can differ among individual tumors, ranging from Mr 90,000 to greater than 400,000. However, in seminal plasma from prostate cancer patients, the predominant component recognized by PD41 is the diffuse Mr greater than 400,000 band. It appears that this monoclonal antibody may recognize a prostate carcinoma-associated mucin-like antigen, which is preferentially expressed on prostate carcinomas, and therefore, may be a useful marker to distinguish benign prostate hyperplasia from prostate carcinoma.

Mycoplasma genitalium infection and host antibody immune response in patients infected by HIV, patients attending STD clinics and in healthy blood donors.

Prevalence of Mycoplasma genitalium in humans is still not clear. We have developed a sensitive and specific serological assay for M. genitalium using lipid-associated membrane proteins (LAMPs) as antigens. Antibodies to LAMPs from M. genitalium showed little cross-reactivity to LAMPs from antigenically similar M. pneumoniae. For validity testing, urines from 104 patients were tested by PCR for M. genitalium. All 15 PCR+ patients had M. genitalium-LAMPs antibodies. Moreover, none of 64 antibody-negative patients were PCR+. Serological study of 1800 patients of various diseased groups and healthy blood donors showed M. genitalium was primarily a sexually transmitted microbe that infected patients with AIDS (44.0%), intravenous drugs users with or without HIV infection (42.5%), and also HIV- patients attending STD clinics (42.6%). Only 5.5% HIV- healthy blood donors and 1.3% HIV+ hemophiliacs tested positive. M. genitalium has been associated with acute non-gonococcal urethritis in male patients. However, many sexually active men and women appear to be chronically infected or colonized by the microbe without apparent clinical symptoms and may continue to transmit the organism through sexual contacts.

Spacing and shape of random peaks in non-parametric spectrum estimates.

In this paper, expressions are derived for the expected number of spurious peaks in a spectrum estimate, that is, crossings above a given significance level per frequency unit, as well as the expected width of these peaks. In numerous scientific applications, spectrum estimates are used for the purpose of identifying sinusoidal or modal components, often thinning large sets of candidate frequencies with coincidence detection. Because one always expects numerous false peaks in a spectrum estimate, knowing the expected rate of false peaks helps to decide whether the number observed is abnormal and hence determine the true nature of the process. An example using solar wind data from the Advanced Composition Explorer is given where spectra display pathological numbers of significant peaks, while temporally permuted versions of the data possess spectra with the number expected for a white, Gaussian process. The permutation test is a valuable diagnostic for processes suspected to contain many line components.

Immunohistochemical evaluation of the expression of prostate tumor-association markers in the nude mouse human prostate carcinoma heterotransplant lines PC-82, PC-EW, and PC-EG.

The biotin-avidin immunoperoxidase assay was used to evaluate the expression of several prostate carcinoma-associated markers in formalin-fixed paraffin-embedded tissue sections of three human prostate nude mouse heterotransplant lines PC-82, PC-EW, and PC-EG. In addition to monoclonal antibodies to PSA and PAP, monoclonal antibodies to five other potentially useful markers for prostate carcinomas (TURP-27, Leu-7, 7E11-C5, PSP-19, and PD41) were tested. Tissues from two or more transplant passages were evaluated. The human prostate target antigens were found to be expressed by one or more of the three heterotransplant lines. The PC-82 and PC-EW lines were the most efficient in terms of expression of multiple prostate carcinoma-associated markers and percentage of tumor cells positive for a given prostate antigen. The staining pattern of each marker, in terms of staining intensity, number of tumor cells stained, and staining location, i.e., membrane, cytoplasmic, or ductal secretions, was similar to what has been observed in tissue sections from human prostate carcinomas. The lack of an appropriate model for evaluating the preclinical potential of these Mabs (especially TURP-27, PSP-19, and PD41) makes the findings of this study of considerable importance, and suggests that these human prostate xenografts may be useful models for exploring the diagnostic and therapeutic potential of these anti-prostate carcinoma monoclonal antibodies.

A novel prostate carcinoma-associated glycoprotein complex (PAC) recognized by monoclonal antibody TURP-27.

A prostate carcinoma-associated antigen recognized by MAb TURP-27 was characterized immunohistochemically and biochemically. TURP-27 antigen was found localized in the cell membrane and cytoplasm of the ductal epithelial cells of normal (10%), benign (75-100%) and malignant (20-100%) prostate cells. Fetal prostate tissues were also found to express the TURP-27 antigen, suggesting expression early in development. This antigen was not expressed by non-prostate tumors examined, but significant cross-reactivity was observed in myelinated nerves while minor cross-reactivity was seen in certain lymphocyte subsets, cells in the adrenal medulla and chief cells of stomach. Immunoblotting and biochemical data demonstrated that the TURP-27 antigen is a sialic-acid-containing glycoprotein complex with major molecular species in prostate tissues of 310-250, 180, 140, 115, 95-90, 69, and 40- to 35-kDa. Immunoblotting patterns similar to those observed for prostate tissues were also seen in CNS extracts with the exception of the 69 and 40- to 35-kDa proteins. This prostate carcinoma-associated sialoglycoprotein complex (PAC) recognized by MAb TURP-27 is likely to represent a novel tumor antigen expressed by prostate tumors.