Is human papillomavirus involved in laryngeal neuroendocrine carcinoma?

The purpose of this study was to detect human papillomavirus (HPV) infection in laryngeal neuroendocrine carcinoma (LNEC) and to explore the possible relationship between HPV-induced malignant transformation and prognosis in LNEC. Ten cases of LNEC from a tertiary referral hospital were retrospectively analyzed. Clinical data were subtracted from patients’ files. Pretreatment biopsy material was tested for the presence of HPV6, 11, 16, and 18 using a PCR-based detection method. Immunohistochemical staining was performed for Ki-67, p16^INK4A, and p53 expression. All cases were negative for the low-risk HPV types HPV6 and HPV11 that are associated with laryngeal papillomatosis. High-risk HPV was detected in two cases; an atypical carcinoid was positive for HPV16 and a large-cell neuroendocrine carcinoma for HPV18. Both HPV-positive tumors had a high Ki-67 labeling index. Two of the four cases with a good response to therapy were hrHPV-positive (both HPV DNA positive) compared with none of the five poor responders. Our findings show that HPV may play a role in the pathogenesis of LNEC. The relationship between HPV, improved prognosis and good response to therapy for squamous cell carcinoma of the head and neck may also be true for a subset of LNEC.     

The post-antibiotic effect defined by bacterial morphology

Three strains of Escherichia coli were incubated with either ciprofloxacin or ampicillin. Filamentation of bacteria was observed after 1-2 h. After 5 h of contact with either drug the percentage of filaments exceeded 90%. The organisms were washed and incubated on drug free medium. Antibiotics when bound to an enzyme render that enzyme inactive; upon removal of the organisms from the antibiotic, the synthesis of enzymes resumes. The period of time encompassing the inactive enzymatic state of the organism at the time of removal from the drug to the time that enzymes restore complete function is our definition of the post-antibiotic effect (pae). Bacterial morphology reflects the variations in activity of these enzymes. The pae was determined by both the morphology of the organisms and the current growth kinetic method. The presence of 10% filaments and 90% bacilli was selected to indicate the endpoint of the pae by morphological criteria. The pae by morphology was 4 h for ciprofloxacin and 3 h for ampicillin. By the growth kinetics method it was 2 h for ciprofloxacin and zero for ampicillin.     

Salmonella susceptibility patterns in hospitals from 1975 through 1984.

The susceptibility of salmonella to commonly used antibiotics was analyzed for the 10-year period 1975 through 1984. The susceptibilities of 19,200 strains isolated from a yearly average of 211 hospitals nationwide and 1,508 strains isolated at the Kings County Medical Center in Brooklyn, N.Y., were described. Nationally, the susceptibility to nine antibacterial agents, including tetracycline, did not change markedly for the decade. The slight increase in susceptibility to tetracycline observed nationally may reflect the decreased clinical use of this antibiotic during the decade studied.     

Antimicrobial agent susceptibility patterns of bacteria in hospitals from 1971 to 1982.

Bacterial susceptibility to 16 commonly used antibiotics was analyzed for a 12-year period (from 1971 to 1982, inclusive). Susceptibilities of 5,828,243 strains isolated from a mean of 242 hospitals nationwide and of 194,575 strains isolated at the Massachusetts General Hospital, Boston, Mass., and the Bronx Lebanon Hospital Center, New York, N.Y., were compared. Strains of Escherichia coli, Staphylococcus aureus, Haemophilus influenzae, and Pseudomonas aeruginosa showed virtually the same susceptibilities to antibiotics throughout the 12-year period, whereas Streptococcus faecalis and Staphylococcus epidermidis showed significant increases in resistance to most antibiotics. The close similarity between antibiotic susceptibilities shown at both the 242 hospitals and the 2 individual hospitals suggests that this analysis accurately reflects trends of bacterial resistance to antibiotics in U.S. hospitals. Since most of the species analyzed produce serious disease and high mortality, their susceptibility to antibiotics is relevant both to physicians treating infectious diseases and to epidemiologists.     

Increased BBB permeability by parasympathetic sphenopalatine ganglion stimulation in dogs

The blood-brain barrier (BBB) is a major obstacle for movement of large molecules to and from the brain. Stimulation of the sphenopalatine ganglion (SPG), the major source of parasympathetic innervation to brain vasculature, is known to vasodilate brain vessels, and has recently been shown to also increase the permeability of the BBB in the rat. In this work, we studied the effect of SPG stimulation on BBB permeability in larger animals--Beagle dogs. Left SPG was exposed by lateral approach in five Beagle dogs, and stimulated at 10 Hz. FITC labeled 10 kDa dextran was continuously infused to the left atrium during stimulation, and cerebral angiography was periodically obtained via the vertebral artery. Three control dogs received labeled dextran, without SPG exposure or stimulation. Brains were perfused with saline thoroughly at the end of stimulation, and samples from various regions were taken for fluorescence reading of tissue homogenates. Cerebral vasodilatation was evidenced in all but one dog, whose fluorescence results were consequently excluded from analysis, assuming that its SPG had been damaged by surgery. Fluorescence was significantly higher in the four stimulated compared to the three non-stimulated animals; e.g. mean FITC-dextran concentration in the anterior brain regions was 0.98+/-0.12 ug (mean+/-S.D.) FITC/g brain for experimental animals, and 0.40+/-0.02 for controls (p<0.01). No effect was seen in the pons and cerebellum (0.68+/-0.22 vs. 0.60+/-0.03, NS) whose vascular innervation is supplied by the otic rather than the SPG ganglion. SPG stimulation appears to be an effective way to increase BBB permeability, allowing introduction of large molecules to the brain. This could be a therapeutic method for a wide variety of brain disorders, including tumors and neurodegenerative diseases.     

Factors associated with the development of psychiatric illness in children with early speech/language problems

This paper reports on the correlates of psychiatric illness in children with speech and language disorders. Of 600 children selected from a community speech clinic, 50% were found to have diagnosable psychiatric disorders according to DSM-III criteria. These psychiatrically ill children were compared to the psychiatrically well children in the sample on a variety of developmental, socioeconomic, medical, and psychosocial factors. Although some differences were found between the well and ill children in other factors, the majority of the differences, and the most highly significant differences, were found in areas of linguistic functioning. It is hypothesized that this finding may be relevant not only to understanding the association between linguistic and psychiatric functioning but also to predicting the outcome and planning treatment for childhood speech and language disorders.     

Identification and validation of WISP1 as an epigenetic regulator of metastasis in oral squamous cell carcinoma

Lymph node (LN) metastasis is the most important prognostic factor in oral squamous cell carcinoma (OSCC) patients. However, in approximately one third of OSCC patients nodal metastases remain undetected, and thus are not adequately treated. Therefore, clinical assessment of LN metastasis needs to be improved. The purpose of this study was to identify DNA methylation biomarkers to predict LN metastases in OSCC. Genome wide methylation assessment was performed on six OSCC with (N+) and six without LN metastases (N0). Differentially methylated sequences were selected based on the likelihood of differential methylation and validated using an independent OSCC cohort as well as OSCC from The Cancer Genome Atlas (TCGA). Expression of WISP1 using immunohistochemistry was analyzed on a large OSCC cohort (n = 204). MethylCap‐Seq analysis revealed 268 differentially methylated markers. WISP1 was the highest ranking annotated gene that showed hypomethylation in the N+ group. Bisulfite pyrosequencing confirmed significant hypomethylation within the WISP1 promoter region in N+ OSCC (P = 0.03) and showed an association between WISP1 hypomethylation and high WISP1 expression (P = 0.01). Both these results were confirmed using 148 OSCC retrieved from the TCGA database. In a large OSCC cohort, high WISP1 expression was associated with LN metastasis (P = 0.05), disease‐specific survival (P = 0.022), and regional disease‐free survival (P = 0.027). These data suggest that WISP1 expression is regulated by methylation and WISP1 hypomethylation contributes to LN metastasis in OSCC. WISP1 is a potential biomarker to predict the presence of LN metastases. © 2015 Wiley Periodicals, Inc.     

Cortactin expression predicts poor survival in laryngeal carcinoma

Amplification of the 11q13 region is one of the most frequent aberrations in squamous cell carcinomas of the head and neck region (HNSCC). Amplification of 11q13 has been shown to correlate with the presence of lymph node metastases and decreased survival. The 11q13.3 amplicon carries numerous genes including cyclin D1 and cortactin. Recently, we reported that FADD becomes overexpressed upon amplification and that FADD protein expression predicts for lymph node positivity and disease-specific mortality. However, the gene within the 11q13.3 amplicon responsible for this correlation is yet to be identified. In this paper, we compared, using immunohistochemical analysis for cyclin D1, FADD and cortactin in a series of 106 laryngeal carcinomas which gene correlates best with lymph node metastases and increased disease-specific mortality. Univariate Cox regression analysis revealed that high expression of cyclin D1 (P=0.016), FADD (P=0.003) and cortactin (P=0.0006) predict for increased risk to disease-specific mortality. Multivariate Cox analysis revealed that only high cortactin expression correlates with disease-specific mortality independent of cyclin D1 and/or FADD. Of genes located in the 11q13 amplicon, cortactin expression is the best predictor for shorter disease-specific survival in late stage laryngeal carcinomas.