Use of the monoclonal antibody MOC-31 as an immunomarker for detecting metastatic adenocarcinoma in effusion cytology

BACKGROUND:

MOC‐31 is an established immunologic marker with which to detect adenocarcinomas. The objective of the current study was to evaluate the use of MOC‐31 in the diagnosis of metastatic adenocarcinoma in effusion specimens.

METHODS:

The authors evaluated cytologic specimens of effusions/washings in which MOC‐31 immunostaining was performed on unstained cell block sections or Papanicolaou‐stained cytospin preparations. Membranous staining with or without cytoplasmic staining was considered to be positive. The immunostaining results were correlated with the cytologic diagnoses and clinical follow‐up data.

RESULTS:

A total of 215 effusions and washings were identified (cell blocks in 162 cases, cytospin preparations in 53 cases, and both in 2 cases in which MOC‐31 immunostaining was performed). A total of 94 (44%) of the 215 cases were found to be positive for malignancy, including 87 metastatic adenocarcinomas. Specimens were positive for MOC‐31 in 76 (87%; 55 cell blocks and 21 cytospin preparations) of 87 cases of metastatic adenocarcinoma. Eleven cases of metastatic adenocarcinoma were found to be negative for MOC‐31 (4 cases from lung tumors, 2 from stomach tumors, 2 from colon tumors, 2 from breast tumors, and 1 from a renal tumor). Minimal and/or focal cytoplasmic staining for MOC‐31 was noted in 13% of cases of reactive mesothelial cells/mesothelioma. The sensitivity of MOC‐31 for metastatic adenocarcinoma was 89%, the specificity was 100%, the negative predictive value was 92%, and the positive predictive value was 100%.

CONCLUSIONS:

MOC‐31 alone was found to be highly sensitive for distinguishing reactive mesothelial cells/mesothelioma from metastatic adenocarcinoma in effusion specimens. Interpreting membranous MOC‐31 staining as positive can help prevent confusion between reactive mesothelial cells/mesothelioma and metastatic adenocarcinoma. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society     

Thromboxane A2 receptor and MaxiK-channel intimate interaction supports channel trans-inhibition independent of G-protein activation

Large conductance voltage- and calcium-activated potassium channels (MaxiK, BK_Ca) are well known for sustaining cerebral and coronary arterial tone and for their linkage to vasodilator β-adrenergic receptors. However, how MaxiK channels are linked to counterbalancing vasoconstrictor receptors is unknown. Here, we show that vasopressive thromboxane A2 receptors (TP) can intimately couple with and inhibit MaxiK channels. Activation of the receptor with its agonist trans-inhibits MaxiK independently of G-protein activation. This unconventional mechanism is supported by independent lines of evidence: (i) inhibition of MaxiK current by thromboxane A2 mimetic, U46619, occurs even when G-protein activity is suppressed; (ii) MaxiK and TP physically associate and display a high degree of proximity; and (iii) Förster resonance energy transfer occurs between fluorescently labeled MaxiK and TP, supporting a direct interaction. The molecular mechanism of MaxiK–TP intimate interaction involves the receptor''s first intracellular loop and C terminus, and it entails the voltage-sensing conduction cassette of MaxiK channel. Further, physiological evidence of MaxiK–TP physical interaction is given in human coronaries and rat aorta, and by confirming TP role (with antagonist SQ29,548) in the U46619-induced MaxiK inhibition in human coronaries. We propose that vasoconstrictor TP receptor and MaxiK-channel direct interaction facilitates G-protein–independent TP to MaxiK trans-inhibition, which would promote vasoconstriction.     

Effect of drying processes and curing time of chitosan-lysine semi-IPN beads on chlorpheniramine maleate delivery

Beads of semi-interpenetrating polymer network (semi-IPN) have been synthesized from chitosan and lysine with varying amounts of glutaraldehyde solution used as a cross-linker. The cross-linked beads are dried by different drying processes such as air-drying, oven-drying and freeze-drying. These semi-IPNs are characterized under a scanning electron microscope (SEM). Swelling studies of these beads are carried out in different pH (2.0 and 7.4) solutions. The effect of concentration of cross-linking agent and curing period on the swelling as well as on the drug release is analysed. The results indicate that the size of matrix depend on the curing time of beads, concentration of glutaraldehyde and technique of drying. The freeze-dried beads exhibit a relatively higher percentage of swelling in the range of 66-89% as compared to oven-dried beads (53-74%) and air-dried beads (39-61%). The drug loaded beads which are cured for different time intervals followed by drying are tested for in-vitro release of chlorpheniramine maleate (CPM) drug. The rate of drug release from freeze-dried beads is much faster than that from the oven-dried and air-dried beads.     

Simplifying paediatric immunization with a fully liquid DTP–HepB–Hib combination vaccine: Evidence from a comparative time-motion study in India

An observational time-motion study investigated logistic, programmatic and safety-related advantages and limits in the delivery of a fully liquid DTP–HepB–Hib combination vaccine versus a lyophilized combination vaccine requiring reconstitution. The study was conducted in 2006, observing 312 child vaccinations in a tertiary hospital setting in Kolkata, India. The time for vaccination was on average 46 s (35.12%) lower with the fully liquid vaccine (p < 0.05). In addition, the fully liquid combination was easier and potentially safer to handle and as well tolerated as the lyophilized formulation. Fully liquid combination vaccines have the potential to simplify immunization schedules, contribute to better resource management and improve efficiency of immunization programs.     

Prostate specific antigen density correlates with features of prostate cancer aggressiveness

PURPOSE: An increased prostate specific antigen density (serum prostate specific antigen divided by prostate volume) is an established parameter to help determine the need to perform prostate biopsies. A man with a high prostate specific antigen and a normal size prostate gland is more likely to have cancer than a man with the same prostate specific antigen and a large gland. Prostate specific antigen in relation to prostate size should also reflect the volume of cancer in the gland. One group defined clinically unimportant prostate cancer as tumor volume less than 0.5 cc, organ confined disease and Gleason less than 7. Another group noted that at the time of biopsy, a prostate specific antigen density less than 0.15 ng/ml/cc combined with low risk clinical tumor features predicted insignificant cancer. There are limited published validating data on the association of prostate specific antigen density with the criteria for prostate cancer aggressiveness. We tested the association of prostate specific antigen density with features of tumor aggressiveness in a screened and in a nonscreened cohort of patients with clinically localized prostate cancer treated with radical prostatectomy. MATERIALS AND METHODS: The screened patient cohort included 1,280 patients with screen detected prostate cancer treated from 1990 to 2002 at Washington University, and the nonscreened cohort included 382 patients treated from 2003 to 2004 at Northwestern University. We recorded the clinical and pathological tumor parameters in a prospective database. Parameters evaluated were pathological tumor stage, Gleason sum, tumor volume, biochemical progression and the previously mentioned 2 criteria for clinically unimportant cancers. We grouped patients into 4 prostate specific antigen density categories of less than 0.1, 0.1 to 0.14, 0.15 to 0.19 and greater than 0.19 ng/ml/cc. RESULTS: There was a significant trend for worsening clinicopathological prognostic features as prostate specific antigen density increased. There were 357 (82%), 283 (75%), 171 (75%) and 192 (55%) men with organ confined disease with clear surgical margins if prostate specific antigen density was less than 0.1, 0.1 to 0.14, 0.15 to 0.19 and greater than 0.19 ng/ml/cc, respectively (p <0.001). There were 86 (20%), 102 (27%), 64 (28%) and 157 (45%) men with a Gleason sum greater than 7 when grouped into each increasing PSA density category, respectively (p <0.001). There were 91 (21%), 91 (25%), 74 (33%) and 157 (46%) men with a total cancer volume greater than 0.5 cc when grouped into each increasing PSA density category, respectively (p <0.001). Prostate specific antigen velocity was greater than 2 ng/ml per year in 11%, 30%, 27% and 46% of men if prostate specific antigen density was less than 0.1, 0.1 to 0.14, 0.15 to 0.19 and greater than 0.19 ng/ml/cc, respectively (p <0.001). CONCLUSIONS: Prostate specific antigen density measurements are useful in helping to determine the aggressiveness of clinically localized prostate cancer, and can be used as an adjunct in predicting insignificant cancer and outcomes after local therapy.     

Degenerative lumbar spinal stenosis—results of expansive laminoplasty

Expansive laminoplasty, a procedure used more and more often for cervical myelopathy, was carried out in patients with lumbar spinal stenosis in the Department of Orthopaedics, Paraplegia, Physical Medicine and Rehabilitation of our institute. Twenty-five such clinico-radiologically proven cases were operated upon. For radiological evaluation, computed tomography (CT) was used. Expansive laminoplasty decompresses the nerve roots by osteoplastic enlargement of the lumbar spinal canal, with the maintenance of spinal stability. These advantages were confirmed during the follow-up of 3 to 5 years. Using CT, the spinal canal was found to be enlarged to a nearly rectangular shape and the average enlargement was 124%. The visual analogue scale (VAS) was used for subjective pain assessment before and after the surgery. The ultimate outcome was assessed by the Surin et al. criteria (Spine 17:1-8, 1992).