Some dissociating factors in the analysis of structural and functional progressive damage in open-angle glaucoma.

AIM: To identify the presence, and origin, of any "dissociating factors" inherent to the techniques for evaluating progression that mask the relationship between structural and functional progression in open-angle glaucoma (OAG). METHODS: 23 patients (14 with OAG and 9 with ocular hypertension (OHT)) who had received serial Heidelberg Retina Tomograph (HRT II) and Humphrey Field Analyser (HFA) examinations for >or=5 years (mean 78.4 months (SD 9.5), range 60-101 months) were identified. Evidence of progressive disease was retrospectively evaluated in one eye of each patient using the Topographic Change Analysis (TCA) and Glaucoma Progression Analysis (GPA) for the HRT II and HFA, respectively. RESULTS: Six patients were stable by both techniques; four exhibited both structural and functional progression; seven exhibited structural progression, only, and six showed functional progression, only. Three types of dissociating factors were identified. TCA failed to identify progressive structural damage in the presence of advanced optic nerve head damage. GPA failed to identify progressive functional damage at stimulus locations, with sensitivities exhibiting test-retest variability beyond the maximum stimulus luminance of the perimeter, and where a perimetric learning effect was apparent. CONCLUSION: The three dissociating factors accounted for nine of the 13 patients who exhibited a lack of concordance between structural and functional progressive damage.

Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial.

OBJECTIVE: Osteoarthritis (OA) is the most common form of arthritis and the second most common cause of long-term disability among middle-aged and older adults in the United States. Methylsulfonylmethane (MSM) is a popular dietary supplement used as a single agent and in combination with other nutrients, and purported to be beneficial for arthritis. However, there is paucity of evidence to support the use of MSM. METHODS: A randomized, double-blind, placebo-controlled trial was conducted. Fifty men and women, 40-76 years of age with knee OA pain were enrolled in an outpatient medical center. Intervention was MSM 3g or placebo twice a day for 12 weeks (6g/day total). Outcomes included the Western Ontario and McMaster University Osteoarthritis Index visual analogue scale (WOMAC), patient and physician global assessments (disease status, response to therapy), and SF-36 (overall health-related quality of life). RESULTS: Compared to placebo, MSM produced significant decreases in WOMAC pain and physical function impairment (P<0.05). No notable changes were found in WOMAC stiffness and aggregated total symptoms scores. MSM also produced improvement in performing activities of daily living when compared to placebo on the SF-36 evaluation (P<0.05). CONCLUSION: MSM (3g twice a day) improved symptoms of pain and physical function during the short intervention without major adverse events. The benefits and safety of MSM in managing OA and long-term use cannot be confirmed from this pilot trial, but its potential clinical application is examined. Underlying mechanisms of action and need for further investigation of MSM are discussed.

Dual blockade of EGFR and ERK1/2 phosphorylation potentiates growth inhibition of breast cancer cells.

One of the major targets for breast cancer therapy is the epidermal growth factor receptor (EGFR) and related receptors, which signal via different signal transduction pathways including the mitogen-activated protein kinase (MAPK) pathway. This study determined whether there is a correlation between EGFR/HER2 status and MAPK (ERK1/2) phosphorylation in breast cancer cells, and how this affects the response to an inhibitor of the receptors. Expression of EGFR, HER2 and phosphorylated ERK1/2 were measured by immunoblotting in a panel of breast cancer cell lines. Several lines expressed high levels of pERK1/2, with no obvious correlation with the level of EGFR/HER2. The EGFR tyrosine kinase inhibitor PKI166 inhibited growth and induced apoptosis in some cells with high levels of growth factor receptors (MDA-MB-468, SUM149, SKBR3), but was less effective in cells that also had high basal ERK1/2 activity (MDA-MB-231). The combination of an inhibitor of MAPK signalling (U0126) and PKI166 produced significantly more inhibition and apoptosis than either agent alone. This suggests that constitutive activation of the MAPK pathway may bypass inhibition of EGFR/HER2 tyrosine kinases, and lead to insensitivity to agents targeting the receptors. However, inhibiting both EGFR/HER2 and MAPK signalling can result in significant growth inhibition and apoptosis of EGFR-expressing breast cancer cells.

Treatment of metal-contaminated water and vertical distribution of metal precipitates in an upflow anaerobic bioreactor.

A lab-scale upflow anaerobic bioreactor filled with granular sludge and cow manure was operated for 140 days to determine the mechanism of metal removal and the vertical distribution of metal precipitates. Heavy metal ions were removed in the order of Cu2+, Cd2+, Zn2+, Fe2+ and Mn2+ with respect to the height in the reactor. The solid phase analysis showed that the heavy metals were mostly precipitated in the form of metal sulfides by sulfate reduction The contents of metal precipitates in the reactor were as follows: (i) Cd and Zn were highest in the bottom, (ii) Fe was highest at the low-middle layer, and (iii) Mn was increased with the height in the reactor. The vertical distribution of metal sulfides in the reactor was directly related to the solubility product (Ksp). Results obtained in this study suggest a feasibility of the application to separate precipitation metal-containing wastewater.

Fine needle aspiration cytologic findings of breast mucinous neoplasms: differential diagnosis between mucocelelike tumor and mucinous carcinoma.

OBJECTIVE: To report the cytologic findings of mucocelelike tumor and mucinous carcinoma. STUDY DESIGN: All mucinous neoplasms diagnosed by fine needle aspiration and confirmed by histologic examination were reviewed to detect the cytologic findings helpful for the differentiation. The cytologic findings were correlated with the histologic findings. RESULTS: Cytologically, mucinous carcinomas were highly cellular and showed many single epithelial cells and variably formed epithelial cell clusters in abundant extracellular mucin. Malignant cells exhibited round, atypical nuclei; granular chromatin; and small nucleoli. Mucocele like tumor showed low cellularity with scanty, monolayered, small sheets of epithelial cells and abundant, extracellular mucin. Myoepithelial cells were present within the epithelial cell sheets. Tumor cells were usually small, with uniform, round nuclei; fine chromatin; and absence of nucleoli. CONCLUSION: Cytologic findings of mucocelelike tumor and mucinous carcinoma were different in cellularity, shape of cell clusters and nuclear features, although mucocelelike tumors having a carcinoma component were similar to mucinous carcinoma. Awareness of the cytologic findings of breast mucinous neoplasms is important to make a specific diagnosis.

Comparison of patients' experiences during imaging tests of the colon.

BACKGROUND: Physical discomfort, anxiety, embarrassment, and other aspects of patient experience impact on future compliance for colonic imaging tests. Therefore, a prospective study was performed comparing patient experiences during air contrast barium enema (ACBE), flexible sigmoidoscopy, and colonoscopy. METHODS: Immediately after each procedure, patients completed a questionnaire assessing pretest anxiety, difficulty with preparation, pain, cramping, bloating, overall discomfort, loss of dignity, willingness to repeat the test, and overall satisfaction. A follow-up questionnaire was administered within 48 hours. Nurses and physicians also completed questionnaires to assess the provider impression of patient experience. RESULTS: Four hundred ten patients (80 ACBE, 202 sigmoidoscopy, 128 colonoscopy) were prospectively enrolled. Sigmoidoscopy caused more pain than ACBE (Odds ratio [OR] 2.64: 95% CI [1.63, 4.27]) or colonoscopy (OR 1.83: 95% CI [1.21, 2.77]). ACBE and colonoscopy did not differ in the degree of pain. Although overall satisfaction appeared to be similar for all tests, patients were less willing to repeat ACBE than sigmoidoscopy (OR 1.85: 95% CI [1.13, 3.02]) or colonoscopy (OR 1.82: 95% CI [1.07, 3.09]). Initial and follow-up pain ratings by patients were highly correlated (Spearman correlation 0.81); however, correlation of pain assessments between staff and patients was poor (Spearman correlation 0.48). CONCLUSIONS: Sigmoidoscopy was more painful than other colonic imaging modalities. Although ACBE and colonoscopy caused similar pain, patients were less willing to repeat ACBE. In aggregate, the data suggest that patients perceive colonoscopy as the most acceptable colonic imaging procedure. Better methods are required to allow staff to adequately assess discomfort experienced by patients during these procedures.

Persisting antibody reaction in paragonimiasis after praziquantel treatment is elicited mainly by egg antigens.

Antibody responses in serum and cerebrospinal fluid (CSF) samples from patients with active and chronic paragonimiasis and in sera from patients on whom follow-up studies were done after praziquantel treatment were analyzed using antigens of Paragonimus westermani prepared from eggs, metacercariae, juveniles of 4- and 7-week old, adult worms and recombinant protein of 28 kDa cruzipain-like cysteine protease (rPw28CCP). The patient sera/CSFs of active and chronic paragonimiasis revealed strong antibody reactions against the crude extracts of 4- and 7-week old juveniles as well as against those from egg and adult. rPw28CCP also showed specific reaction to the sera with active paragonimiasis. After the treatment, levels of specific antibodies in the sera gradually decreased to negative range in most patients. In some cases with persisting high antibody levels, however, the reactions at 27 kDa egg protein were sustained throughout the observation period of 34 months. The reactions at 35 and 32 kDa in adult extract and rPw28CCP disappeared rapidly after the treatment. Persistent antibody reactions even after successful treatment are provoked by continuous antigenic challenge from eggs which were not resolved by treatment.

Do we practice what we preach? clinical decision making and utilization of endoscopic ultrasound for staging esophageal cancer.

OBJECTIVES: Endosonography is accurate for staging esophageal cancer. However, whether detailed staging impacts clinical decision making, whether endosonography is perceived as a useful modality, and what factors influence the utilization of endosonography have not been studied. METHODS: One hundred gastroenterologists were surveyed about staging and management of esophageal cancer, including: 1) management by stage; 2) perceived usefulness of endosonography; 3) availability of endosonography; and 4) number of patients referred. RESULTS: Clinical decisions varied by incremental differences in tumor stage. However, only 27 of 66 respondents (40.9%) judged endosonography to be very useful or essential for the evaluation of esophageal cancer and only 22 (33.3%) had referred a patient. Perceived usefulness and availability were independent factors strongly associated with referral for endosonography. Among 18 respondents to whom endosonography was available and who considered it useful, 14 (77.9%) had referred a case. In contrast, a conservative management was not associated with either perceived usefulness of or referral for endosonography. CONCLUSIONS: Clinicians recognize the importance of detailed staging for management of esophageal cancer. Despite this, they underestimate the utility of endosonography and fail to refer patients for appropriate evaluation. Lack of perceived usefulness and unavailability are important independent barriers to utilization of endosonography in clinical practice.

Discrepancy between sex- and water-associated risk behaviors for cryptosporidiosis among HIV-infected patients in San Francisco.

OBJECTIVE: Potential transmission of cryptosporidiosis through drinking water supplies has been highly publicized; however, it is unknown whether this reporting has increased patient awareness or reduced other risk behaviors for exposure to this organism, such as high-risk sexual behavior. METHODS: Consecutive patients presenting for initial evaluation to the Gastroenterology AIDS Clinic completed a questionnaire that assessed knowledge about cryptosporidiosis, perceived risk of infectious diarrhea, drinking water sources, and high-risk sexual behavior. RESULTS: Fifty-one patients completed the questionnaire (82% male; 86% homosexual; mean age, 38 years; median CD4 count, 136 x 10(6) cells/L). Most respondents (31 of 44; 70%) believed they were at risk for infectious diarrhea. Awareness of cryptosporidiosis was high (31 of 45; 69%) as was avoidance of tap water (26 of 51; 51%) and exclusive or frequent use of bottled or boiled water (40 of 51; 78%). Respondents who used bottled water reported spending an average of $331.76 U.S. annually. However, high-risk sexual behavior remained common: 21 (41%) of the 51 subjects reported unprotected anal intercourse or oral-anal sexual contact. High-risk sexual behavior was prevalent even among subjects who drank exclusively boiled or bottled water. CONCLUSIONS: Awareness of risk for infectious diarrhea and cryptosporidiosis is high among patients infected with HIV in San Francisco. Patients perceive drinking water to be a substantial risk factor for infectious diarrhea and incur significant expense to avoid tap water. However, high-risk sexual behaviors remain prevalent in this population and should be the focus of future education efforts.

Highly absorptive coating for the vacuum ultraviolet range.

We have developed new, highly absorptive coatings for the vacuum UV wavelength range. These coatings display two distinct granularity scales: large structures of a 10-100-microm scale form efficient light traps, upon which are superimposed structures of a submicrometer scale. We present results for the total hemispherical reflectivity at normal incidence for 121.6 nm and at a grazing angle incidence for 17.1, 30.4, 58.4, and 121.6 nm. These measurements were made for the new coatings as well as for various coatings in common use. Absorption of the new coatings is in some cases higher than for the best-known coatings and, in contrast to the latter, they are mechanically robust.

Variation of antigenic proteins of eggs and developmental stages of Paragonimus westermani.

Diagnosis of early paragonimiasis is difficult because parasitological evidence is not easily obtained. Antibody tests have been proposed as a good substitute for classical diagnostic techniques. Using the crude extracts of Paragonimus westermani eggs, metacercariae, 4- and 7-week juveniles, and 16-week adults as antigens, we observed the early antibody responses. Sera were obtained from 4 experimental cats, fed 50 metacercariae each, at intervals until 13 weeks post-infection. Antibody (IgG) responses were identified by ELISA using extracts of 4-week juveniles, followed by those of 7- and 16-week worms. Antibody responses were minimal against the metacercarial extracts. Antibodies to P. westermani egg extracts were elevated after 10 weeks post-infection. In immunoblot analysis, more than nine protein bands in 4-week juveniles reacted with the early infection sera. Antigenic proteins in adult worms were different from those of juveniles. After four weeks of infection, 32 and 35 kDa bands in the adult extracts were increasingly reactive. Egg specific proteins at 28, 46 and 94 kDa were reactive only after 10 weeks. Antigenic components reacting to the early infection sera changed during the maturation stages of P. westermani; almost all juvenile antigens were replaced by adult antigen components.

Locus of control as a stress moderator and mediator in children of divorce.

This paper examined the stress moderator and mediator effects of four dimensions of perceived control in children of divorce. The dimensions of locus of control included internal control for positive events, internal control for negative events, unknown control for positive events, and unknown control for negative events. The sample consisted of 222 children between the ages of 8 and 12 whose parents had divorced in the previous 2 years. Moderational analyses showed that unknown control for positive events interacted with negative events to predict total symptoms. Plots of the simple slopes indicated a stress buffering effect whereby the slope of negative events on symptoms was higher for high than for low levels of unknown control for positive events. Mediational analysis showed that the relations between negative events and symptoms were mediated by both unknown control for positive events and unknown control for negative events. In contrast, evidence was not found for either a stress mediational or a moderational model for perceived internal control for positive or negative events. These results suggest that unknown control beliefs may be a particularly important dimension of control for children of divorce.