Helicobacter pylori seropositivity is associated with antinuclear antibodies in US adults, NHANES 1999-2000.

Infectious diseases, such as Helicobacter pylori, which produce systemic inflammation may be one key factor in the onset of autoimmunity. The association between H. pylori and antinuclear antibodies (ANA), a marker of autoimmunity, has been understudied. Data from the 1999-2000 National Health and Nutrition Examination Survey were used to evaluate the cross-sectional association between H. pylori seroprevalence and ANA positivity in US adults aged ≥20 years. ANA was measured in a 1:80 dilution of sera by indirect immunofluorescence using HEp-2 cells (positive ⩾3). H. pylori immunoglobulin G enzyme-linked immunosorbent assays were used to categorise individuals as seropositive or seronegative. H. pylori seropositivity and ANA positivity were common in the adult US population, with estimated prevalences of 33.3% and 9.9%, respectively. Both were associated with increasing age. H. pylori seropositivity was associated with higher odds of ANA (prevalence odds ratio = 1.89, 95% confidence interval = 1.08-3.33), adjusted for age, sex, race/ethnicity, educational attainment and body mass index. H. pylori infection may be one key factor in the loss of self-tolerance, contributing to immune dysfunction.

Reliability of shear wave ultrasound elastography for neck lesions identified in routine clinical practice.

PURPOSE: To evaluate the reliability of shear wave ultrasound elastography (SWE) in the neck. MATERIALS AND METHODS: 176 neck lesions (40 thyroid, 56 lymph nodes, 46 salivary, 34 miscellaneous) identified in a routine US clinic underwent SWE by one or two blinded radiologists. For this study, SWE required the operator to acquire three 10 second dynamic colour-coded SWE cineloops per lesion, select one static image per cineloop, and place circular regions-of-interest within the entire lesion and stiffest part to generate 3 SWE measurements per static image. For logistical reasons, one radiologist evaluated all 176 lesions and the other evaluated 58 lesions. Both radiologists also reviewed 27 archived cineloops independently to assess SWE excluding practical technique. Reliability was assessed using intraclass correlation coefficients (ICCs) concordance correlation coefficients (CCCs) and coefficients of repeatability (CORs). RESULTS: Test-retest ICCs for the radiologist evaluating 176 lesions were 0.78 - 0.85 (fair-excellent agreement), CCCs were 0.85 - 0.88 (substantial agreement), and CORs were 14.9 - 36.1 kPa. For both radiologists evaluating 58 lesions, intra-rater and inter-rater ICCs were 0.65 - 0.78 and 0.72 - 0.77 respectively. For SWE excluding practical technique, inter-rater ICCs were 0.97 - 0.98 (excellent agreement). ICCs differed according to tissue, being higher in thyroid lesions than lymph nodes (p < 0.001), and higher in benign than malignant lesions (p values < 0.001). CONCLUSION: Intra- and inter-rater reliability of SWE is fair to excellent according to ICCs. SWE reliability is influenced appreciably by acquisition technique. Nevertheless, CORs for SWE are not negligible. To determine whether these results are acceptable clinically, further research is required to establish SWE stiffness values of normal and pathological tissues in the neck.

Fear of falling and associated activity curtailment among middle aged and older adults with multiple sclerosis.

The purpose of this study was to identify factors associated with increased likelihood of reporting fear of falling (FoF) among people with multiple sclerosis (MS) and factors associated with activity curtailment among the subset of individuals reporting FoF. Cross-sectional data from telephone interviews with 1064 individuals with MS, aged 45-90 years living in the Midwestern United States were used. Logistic regression models examined factors associated with FoF and with activity curtailment among individuals reporting FoF. Of the participants, 63.5% reported FoF. Increased likelihood of reporting FoF was associated with being female, experiencing greater MS symptom interference during everyday activities, history of a fall in the past 6 months, and using a walking aid. Among participants reporting FoF, 82.6% reported curtailing activity. Increased likelihood of activity curtailment among people reporting FoF was associated with using a walking aid, needing moderate or maximum assistance with instrumental activities of daily living, and having less than excellent self-reported mental health. We concluded that FoF and associated activity curtailment are common among people aged 45-90 with MS. While FoF and associated activity curtailment may be appropriate responses to fall risk, the findings suggest that factors beyond realistic appraisal of fall risk may be operating.

Protective effect of polysaccharides-enriched fraction from Angelica sinensis on hepatic injury.

A polysaccharides-enriched fraction from the root of Angelica sinensis, which is known for its antiulcer action on the gastrointestinal tract, was isolated and studied for its hepato-protective effect in rodents. Intra-gastric administration of Angelica sinensis polysaccharides-enriched fraction (AP) at the doses of 50 or 75 mg/kg dose-dependently prevented liver toxicity induced by acetaminophen in mice but did not affect the serum acetaminophen concentration. It normalized the rises of serum alanine transferase (ALT) and hepatic nitric oxide synthase (NOS) activities and the decrease of glutathione level in the liver. It also reduced the hepatic malondialdehyde (MDA) concentration. The protective effect was less evident in the carbon tetrachloride (CCl4)-treated animals including mice and rats. In the rat the elevated serum ALT level was unaffected though the MDA level was similarly reduced by the higher dose of AP. In these animals, CCl4 increased the hepatic glutathione level instead while the NOS activity remained unchanged. These findings suggest that the pathogenic mechanisms of both acetaminophen and CCl4 are different. AP is more effective in the protection against liver damage induced by acetaminophen, which is associated with the glutathione depletion and nitric oxide synthase activation in the liver.

Disodium cromoglycate inhibits production of immunoglobulin E.

Disodium cromoglycate (DSCG) has been shown to inhibit the release of mediators from mast cells. In the present study, the effect of DSCG on active anaphylactic reaction was studied in mice. DSCG dose-dependently inhibited the active systemic anaphylactic reaction and serum immunoglobulin (Ig)E production induced by immunization with ovalbumin, Bordetella pertussis toxin and aluminum hydroxide gel. DSCG strongly inhibited IL-4-dependent IgE production by lipopolysaccharide-stimulated murine whole spleen cells. In the case of U266 human IgE-bearing B cells, DSCG also showed an inhibitory effect on the IgE production. These results suggest that DSCG has an anti-anaphylactic activity by inhibition of IgE production from B cells.

Protein kinase C independent activation of inducible nitric oxide synthase by tumor necrosis factor-alpha in TM4 Sertoli cells.

To investigate the nitric oxide (NO) production and its signalling mechanism in TM4 Sertoli cells, the cells were treated with recombinant tumor necrosis factor-alpha (rTNF-alpha), recombinant interleukin-1 alpha (rIL-1alpha), or lipopolysaccharide (LPS), either alone or in combination with recombinant interferon-gamma (rIFN-gamma), and NO production was measured by using the Griess method. TM4 Sertoli cells produced a small amount of NO upon treatment with rIFN-gamma. The effect of rIFN-gamma was drastically increased by cotreatment with rTNF-alpha in a dose-dependent manner. However, combination of rIL-1alpha or LPS with rIFN-gamma did not synergize to activate cells. RIFN-gamma in combination with rTNF-alpha showed marked increase of the expression of iNOS protein. Protein kinase C inhibitors did not inhibit the production of NO induced by rIFN-gamma plus rTNF-alpha. These results suggest that the role of TNF-alpha is to provide TM4 Sertoli cells with the active cofactor for NO production and TNF-alpha-induced signaling for induction of NO synthesis is not dependent on protein kinase C activation.

Lesions of the intermediate medial hyperstriatum ventrale impair sickness-conditioned learning in day-old chicks.

Lesion studies show that the intermediate medial hyperstriatum ventrale (IMHV), a forebrain visual association area in chicks, is involved in learning and memory for one-trial passive avoidance and imprinting. We examined the effects of IMHV lesions in a one-trial, nongustatory, sickness-conditioned learning task. This task is similar to passive avoidance and imprinting because all three tasks require the chick to remember visual cues in order to respond correctly. However, sickness-conditioned learning differs from imprinting and passive avoidance because it uses sickness as the aversive stimulus and there is a longer conditioned stimulus-unconditioned stimulus interval (30-min delay compared to seconds). Bilateral IMHV lesions given 24 h before training impaired the ability of the chicks to avoid a bead associated with sickness produced by lithium chloride injection, as did pretraining unilateral left or right IMHV lesions. Post-training IMHV lesions given 1 h after training did not impair avoidance of the test bead in the sickness-conditioned learning task. However, lesioned chicks showed generalized avoidance of all test beads. The pretraining lesion results are similar to those found in imprinting and passive avoidance learning; however, the effects of unilateral IMHV lesions differed. Post-training lesion effects are similar to those found in passive avoidance learning. We propose that both left and right IMHV are necessary for sickness-conditioned learning and that post-training IMHV lesions impair the ability of the chick to learn or remember the association between the color of the bead and the aversive consequences of LiCl injection.

A phase II evaluation of high dose cisplatin and etoposide in patients with advanced esophageal adenocarcinoma.

BACKGROUND: In patients with advanced esophageal adenocarcinoma, the efficacy and palliative role of systemic chemotherapy are not well defined. The primary objective of this Phase II trial was to evaluate the antitumor activity and toxicity of a multiday chemotherapy schedule of high dose cisplatin and etoposide in patients with unresectable or metastatic esophageal adenocarcinoma. A secondary objective was to assess the efficacy of this regimen in palliating dysphagia. METHODS: Twenty-seven eligible patients with unresectable locoregional or metastatic esophageal adenocarcinoma were treated with cisplatin, 30 mg/m2/day, and etoposide, 60 mg/m2/day, intravenously daily for 5 days, every 3 weeks. After three cycles of chemotherapy, all patients were assessed for response. Patients with responding metastatic disease were given one additional cycle of chemotherapy, and patients with locoregional disease received radiation and concurrent continuous infusion of 5-fluorouracil at 300 mg/m2/day for the duration of radiation therapy. Patients were questioned about dysphagia symptoms initially and then weekly during chemotherapy. RESULTS: The major toxicities included myelosuppression, nausea and vomiting, and peripheral sensory neuropathy, with one treatment-related death. Major responses were observed in 13 patients (48%; 95% confidence intervals, 36-74%), including 5 complete and 8 partial responses. Dysphagia relief occurred in 89% of 18 symptomatic patients within a median time of 16 days. The median survival duration for all patients was 9.8 months, and the actuarial 3-year survival rate was 22%. CONCLUSIONS: Multiday chemotherapy with high dose cisplatin and etoposide is active in patients with advanced esophageal adenocarcinoma. Toxicities associated with this regimen are substantial but manageable.

Decline of posttreatment tumor marker levels after therapy of nonsmall cell lung cancer. A useful outcome predictor.

BACKGROUND: The assessment of treatment efficacy in nonsmall cell lung cancer (NSCLC) is limited by the lack of a clear association between clinical response and survival. The prognostic usefulness of treatment-induced tumor-marker declines in NSCLC has not been established. The authors investigated the prognostic significance of treatment-induced declination in tumor marker levels of carcinoembryonic antigen, CA 19-9, and CA 125 in a group of patients with NSCLC treated with a brief course of cisplatin-based chemotherapy. METHODS: Eighty-three patients with NSCLC enrolled on 2 related treatment protocols had pretreatment tumor-marker determinations. Patients were restaged 10 to 12 weeks after study entry, and clinical and marker responses were determined. RESULTS: Thirty-eight patients (46%) had elevated pretreatment tumor markers, 36 (42%) of whom were evaluable for both clinical and marker responses. Pretreatment, the latter 36 individuals had measurable or evaluable disease, and at least one elevated tumor marker (greater than twice normal); posttreatment, they had follow-up measurements of both parameters. Of the 36 patients, 8 had normalization of tumor marker levels, 13 had 50-99% marker level declination, and 15 had less than 50% or no declination. In the same group of 36 patients, there were, 1 patient with complete clinical response, 11 with partial response, 19 with stable disease, and 5 with progressive disease. Marker responses occurred with equal frequency in clinical responders and nonresponders. There was no association between clinical response and survival, but there was a strong association between marker response and survival. CONCLUSIONS: In patients with nonsmall cell lung cancer with elevated pretreatment tumor marker levels, treatment-induced marker level declination can be a surrogate indicator for survival.

Squamous-cell carcinoma of the anal canal: management with combined chemo-radiation therapy.

Twenty patients with squamous-cell carcinoma of the anal canal received combined chemo-radiation therapy as their primary treatment. There were 18 women and two men with a mean age of 63 years (range, 34-91 years). The mean follow-up was 34 months (range, 6-62 months). Anal margin cancers and adenocarcinomas were excluded. Fourteen of 20 patients treated had a complete response. There were six local failures: three with residual disease at the end of treatment and three with recurrent disease at a later date. Of the three with residual disease, one underwent abdominoperineal resection and two received salvage therapy (one with chemo-radiation and one with radiation alone). All three patients with recurrent disease were treated with abdominoperineal resection. All six were disease free at the end of the study. Of the 14 patients with complete local response, one presented with liver metastases 19 months later. Sixteen patients (80 percent) were alive at the end of the study, and 19 patients (95 percent) had no evidence of disease. These data add support for salvage therapy in the treatment of patients with residual disease following initial chemo-radiation therapy. Salvage options for patients with squamous-cell carcinoma of the anus who fail the Nigro protocol will be discussed.

Preoperative versus postoperative adjuvant radiotherapy for surgically curable carcinoma of the rectum and distal sigmoid colon.

From January 1979 to October 1986, 86 patients with surgically resectable adenocarcinoma of the rectum or rectosigmoid were treated with adjuvant radiotherapy consisting of preoperative 2,400 cGy (22 patients), preoperative 4,000 cGy (14 patients), "sandwich" technique (27 patients), and postoperative irradiation (23 patients). Average follow-up was 42.9 months. The local recurrence rate was 4.5%, 9.1%, 7.4%, and 34.8%, respectively. The distant metastasis rate was 18.2%, 18.2%, 7.4%, and 30.4%, respectively. Preoperative radiotherapy with adequate surgical resection appears more effective in reducing the incidence of local recurrence.