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Negative symptoms in depressed and schizophrenic patients: how do they differ?

BACKGROUND: The present study evaluated differences in negative symptoms between schizophrenic and depressive patients and investigated whether a consideration of the nature of negative symptoms (enduring vs. nonenduring) can help to improve their specificity for schizophrenia. METHOD: Patients enrolled in the study were consecutively hospitalized with an acute exacerbation of schizophrenia (N = 33) or major depressive disorder (N = 43) (DSM-IV). Negative and depressive symptoms were assessed with the Scale for the Assessment of Negative Symptoms (SANS) and the Montgomery-Asberg Depression Rating Scale, respectively. Duration of negative symptoms was assessed through a semistructured interview with the patients and their closest relatives. On the basis of the assessed duration of symptoms, negative symptoms were categorized as enduring or nonenduring. RESULTS: Analyses revealed high SANS ratings for both diagnostic groups. Negative symptoms in depressive patients (p =.01), but not in schizophrenic patients, were significantly associated with the presence or the emergence of depressive symptoms. The prevalence of enduring negative symptoms was significantly higher in schizophrenic patients than in depressive patients (p <.01). A consideration of enduring negative symptoms significantly increased the discriminative power of negative symptoms for schizophrenia (p =.02). CONCLUSION: The present findings suggest that negative symptoms in most depressive patients are just an epiphenomenon of depressive symptoms and can be distinguished from schizophrenic negative symptoms.

Acute Disease↗

Review of clinical, cytogenetic, and molecular aspects of Ph-negative CML.

Between 1985 and 1989, many cases of Philadelphia (Ph) chromosome negative chronic myelogenous leukemia (CML) were reported. For this review, the following selection criteria were used: the original articles on Ph-negative cases should provide clinical, hematologic, cytogenetic as well as molecular data. In addition, eight unpublished cases of Ph-negative CML are included that were studied in our institute during the last two years. Our purpose was to correlate presence or absence of the Ph rearrangement with the clinical features in an attempt to test whether the entity "Ph-negative CML" really exists and to identify the pathologic characteristics, frequency of occurrence, prognosis for survival, and underlying molecular mechanisms. Data on Ph-negative CML patients were compared with data on Ph-positive CML, atypical CML (aCML), and chronic myelomonocytic leukemia (CMMoL), reported in the same papers as the Ph negative patients. Essential for comparison of data from the different investigators appeared to be a clear description of criteria they used to establish the diagnosis CML, or alternatively a complete presentation of data for all patients reported in the articles. In most cases, Ph-negative CML was distinguishable from CMMoL and aCML, using simple criteria, e.g., differential count of peripheral blood and absence of dysplasia in the bone marrow. Cytogenetic analysis showed normal karyotype in most cases of Ph-negative CML. Interestingly, in cases with abnormal karyotype, chromosome 9 band q34 was relatively frequently involved in translocations with other chromosomes than chromosome 22, suggesting a variant Ph translocation not visible by cytogenetic techniques. This assumption was confirmed by molecular analysis, demonstrating bcr-abl rearrangement in 9 out of 10 of the latter cases. Results of cytogenetic and molecular investigations in 136 cases of Ph-negative CML reviewed in this article clearly indicated that molecular techniques are valuable tools for identification of bcr-abl rearrangements, indicative for the Ph translocation. The different mechanisms responsible for bcr-abl rearrangement in Ph-negative CML patients are discussed. The question remains whether all Ph-negative CML patients will have bcr-abl rearrangements, or whether alternative mechanisms will be identified that are responsible for this disease.

Chromosomes, Human, Pair 22↗

Incidence of cervical cancer following negative smear. A cohort study from Maribo County, Denmark.

In order to estimate the risk of developing cervical cancer among women who originally had cytologically normal Papanicolaou (Pap) smears, information has been collected on all Pap smears taken in Maribo County, Denmark in 1966-1982 among women born 1918-1952. A total of 27,811 women are included in the study, and cases of invasive cervical cancer developed in the study population have been identified from the local department of pathology and from the Danish Cancer Registry. The incidence of cervical cancer has been tabulated by number of previous negative smears and by time elapsed since last negative smear. Women with one previous negative smear have a zero risk of developing cervical cancer during the first year following the negative smear. The incidence among these women increases with length of time since the negative smear and reaches the level of unscreened women during the fifth year of follow-up. Women with 2-4 previous negative smears also have a negligible risk of developing cervical cancer during the first two years following the last negative smear. The incidence among these women increases less over time than the incidence for women with one previous negative smear. No cases of cervical cancer were observed among 7,716 women with 5+ previous negative smears. The study indicates that the 5-year risk of developing cervical cancer is 48% lower in women with one previous negative smear than in an unselected population of unscreened women. The 5-year risk for women with 2-4 previous negative smears is 69% lower than that for unscreened women.

Adult↗

Testing systems for assessment of negative symptoms in schizophrenia.

To compare methods of measuring negative symptoms, eight rating scales were employed to retrospectively assess and subtype 187 patients with schizophrenia from the Chestnut Lodge Follow-up Study. These included Andreasen's Schedule for Assessment of Negative Symptoms, Carpenter's Criteria for the Deficit Syndrome, Kay and Opler's Positive and Negative Symptom Scale, the scales developed by Krawiecka et al and Crow's modification of them, the Negative Symptom Scale developed by Lewine et al, Pogue-Geile and Harrow's Negative Symptom Scale, and Abrams and Taylor's Emotional Blunting Scale. The overlap and concordance, temporal stability, and predictive validity of these instruments are described. When rated from detailed medical records, the reliability of all scales was fair to good. Despite their inclusion of different items, there were high positive correlations between the scales when used to rate negative symptoms dimensionally. When used to classify individual patients as having the negative or deficit syndrome, however, concordance among criteria was low. Using the broadest criteria (Pogue-Geile and Harrow), 75 (40%) patients were diagnosed as having negative syndrome; the narrowest criteria (Andreasen and Olsen) yielded 11 (6%) diagnoses of negative syndrome. Narrower definitions tended to be subsets of broader ones. Carpenter's Criteria for the Deficit Syndrome focus on primary enduring negative symptoms and show the greatest temporal stability. Broader criteria, which diagnose the deficit or negative syndrome independent of severity of positive symptoms, had the greatest predictive validity.

Adult↗

Characterization of triple negative clones isolated from post-natal human thymus.

Human triple negative (CD3- CD4- CD8-) thymocytes and double negative (CD4- CD8-) thymocytes purified from post-natal thymus were cloned with a feeder cell mixture of irradiated PBL, irradiated JY cells and PHA and expanded with IL-2. The cloning efficiency of triple negative thymocytes was less than 1% and the majority of the clones were triple negative. One out of 11 clones was TCR alpha beta+ CD4+. No TCR gamma delta+ clones were isolated. On the other hand, the cloning efficiency of double negative thymocytes was about 10% and most of the clones isolated were TCR gamma delta+. We could not find any evidence of in vitro differentiation of triple negative thymocytes into TCR gamma delta+ cells. Some of the triple negative clones expressed CD16 brightly and were apparently NK cells. All CD16- clones isolated from triple negative thymocytes, however, expressed NKH1, which is also an NK cell marker. Cytoplasmic CD3-delta and CD3-epsilon Ag which have been reported to be expressed in the most immature thymocytes were not detected in any of these clones. Furthermore, the CD16- triple negative clones exhibited significant cytolytic activity against K562. Phenotype of the clones seems to be stable under various conditions in vitro including coculture with human thymic epithelial cells. These data indicate that the CD16- triple negative clones isolated from triple negative thymocytes are similar to a minor subset of NK cells which is CD16- NKH-1+. It is not clear whether they originated from a distinct subset of mature or immature NK cells resident in the thymus tissue or from common precursors of both T and NK lineage.

Antigens, Differentiation, T-Lymphocyte↗

On the difference between response inhibition and negative priming: evidence from simple and selective stopping.

Negative priming is a commonly observed after-effect in studies concerning inhibition. Effects of the preceding trial are also found in other paradigms, like the stop signal paradigm. In the present study, stop signals were introduced in a negative priming paradigm and the relation between stop signal inhibition and negative priming was investigated. In Experiment 1, we used a simple stop signal task. Stopping data clearly suggest that stopping performance was not influenced by negative priming. Interestingly, on no-signal probes the negative priming effect disappeared after successful inhibition of the response on the prime trial. On the contrary, when inhibition failed, the negative priming effect remained. In Experiment 2, we used the selective stop signal task. As in Experiment 1, inhibition of motor responses was not influenced by negative priming. The hypothesis that negative priming disappeared due to a general nonspecific stop was confirmed in this experiment, as a negative priming effect was found after both successful and unsuccessful behavioral inhibition. The results of both experiments show that response inhibition is not influenced by negative priming, and that negative priming is only affected after a successful general stop.

Analysis of Variance↗

Clozapine's effect on negative symptoms in treatment-refractory schizophrenics.

Clozapine has proven to be more effective than typical antipsychotics in treatment-refractory schizophrenic patients, and some evidence suggests that it may be particularly useful in treating the negative symptoms of schizophrenia. However, it is unclear whether this observation reflects improvement in "primary" or "secondary" negative symptoms. We hypothesized that a portion of clozapine's effect on negative symptoms would be related to an improvement in positive (psychotic and disorganization) symptoms, a decrease in extrapyramidal side effects (EPSE), and/or a decrease in depressive symptoms. The remainder of its effect would be related to a direct effect on the neural circuits or pathologic processes responsible for the negative symptoms. Twenty-nine treatment-refractory schizophrenics treated with clozapine for 6 weeks were studied. The core negative symptoms measured by the Scale for the Assessment of Negative Symptoms ([SANS] affective flattening, anhedonia/asociality, avolition/apathy, and alogia) all improved with clozapine treatment. Overall, there was a 31% improvement in negative symptoms, a 32% improvement in psychotic symptoms, and a 35% improvement in disorganization. The improvement in negative symptoms was correlated with improvement in disorganization, but not with improvement in psychotic symptoms, depression, or drug-induced EPSE. Although there was a correlation between improvement in negative symptoms and improvement in disorganization, there was a suggestion that the two are changing in parallel, but are independent of each other. It appears that at least a portion of clozapine's effect on core negative symptoms is mediated through a direct effect on the underlying pathophysiology of schizophrenia associated with negative symptoms.

Adult↗

Differentiation of primary from secondary anti-EBNA-1-negative cases by determination of avidity of VCA-IgG.

BACKGROUND: Serological techniques are used to determine Epstein Barr virus (EBV) etiology of a constellation of signs or symptoms related to lymphadenopathy, fever, respiratory tract infection, mononucleosis, hepatitis, thrombocytopenia or neurological disorder. Anti-Epstein Barr Nuclear antigen (EBNA)-1 is regularly negative during the first 3-4 weeks after the onset of clinical symptoms indicating acute EBV infection (primary anti-EBNA-1-negative). It may, however, also be negative in immunocompromised convalescent individuals (secondary anti-EBNA-1-negative) such as tumor patients, HIV-positive patients and transplant recipients. OBJECTIVES: The aim of this study was to determine the frequency of secondary anti-EBNA-1-negative cases and to find a way to distinguish them from primary anti-EBNA-1-negative cases using anticomplementary immunofluorescence (ACIF) and enzyme immunoassay (EIA). STUDY DESIGN: All sera sent to our institute for EBV serology during one year were routinely tested for Viral Capsid antibody (VCA)-IgM, VCA-IgG and anti-EBNA-1. RESULTS: VCA-IgG-positive/anti-EBNA-1-negative cases (13.5% of total VCA-IgG-positive) comprised 55% primary and 45% secondary anti-EBNA-1-negative cases. Detection of secondary anti-EBNA-1-negative cases was independent of the method used, i.e., ACIF or EIA. VCA-IgG retained its high avidity in secondary anti-EBNA-1-negative cases, whereas primary anti-EBNA-1-negative cases taken during the early phase of acute infection showed low avidity of VCA-IgG. CONCLUSION: Determination of the avidity of VCA-IgG routinely and in concert with standard serodiagnosis (VCA-IgG, VCA-IgM, anti-EBNA-1) can enable the differentiation of primary and secondary anti-EBNA-1-negative cases.

Journal Article↗

Social anxiety and fear of negative evaluation: construct validity of the BFNE-II.

The Brief Fear of Negative Evaluation Scale [BFNE; Leary, M. R. (1983). A brief version of the Fear of Negative Evaluation Scale. Personality and Social Psychology Bulletin, 9, 371-375] is a self-report measure designed to assess fear of negative evaluation, a characteristic feature of social anxiety disorders [Rapee, R. M., & Heimberg, R. G. (1997). A cognitive-behavioral model of anxiety in social phobia. Behaviour Research and Therapy, 35, 741-756]. Recent psychometric assessments have suggested that a 2-factor model is most appropriate, with the first factor comprising the straightforwardly worded items and the second factor comprising the reverse-worded items [Carleton, R. N., McCreary, D., Norton, P. J., & Asmundson, G. J. G. (in press-a). The Brief Fear of Negative Evaluation Scale, Revised. Depression & Anxiety; Rodebaugh, T. L., Woods, C. M., Thissen, D. M., Heimberg, R. G., Chambless, D. L., & Rapee, R. M. (2004). More information from fewer questions: the factor structure and item properties of the original and brief fear of negative evaluation scale. Psychological Assessment, 2, 169-181; Weeks, J. W., Heimberg, R. G., Fresco, D. M., Hart, T. A., Turk, C. L., Schneier, F. R., et al. (2005). Empirical validation and psychometric evaluation of the Brief Fear of Negative Evaluation Scale in patients with social anxiety disorder. Psychological Assessment, 17, 179-190]. Some researchers recommend the reverse-worded items be removed from scoring [e.g., Rodebaugh, T. L., Woods, C. M., Thissen, D. M., Heimberg, R. G., Chambless, D. L., & Rapee, R. M. (2004). More information from fewer questions: the factor structure and item properties of the original and brief fear of negative evaluation scale. Psychological Assessment, 2, 169-181; Weeks, J. W., Heimberg, R. G., Fresco, D. M., Hart, T. A., Turk, C. L., Schneier, F. R., et al. (2005). Empirical validation and psychometric evaluation of the Brief Fear of Negative Evaluation Scale in patients with social anxiety disorder. Psychological Assessment, 17, 179-190]; however [Carleton, R. N., McCreary, D., Norton, P. J., & Asmundson, G. J. G. (in press-a). The Brief Fear of Negative Evaluation Scale, Revised. Depression & Anxiety; Collins, K. A., Westra, H. A., Dozois, D. J. A., & Stewart, S. H. (2005). The validity of the brief version of the fear of negative evaluation scale. Journal of Anxiety Disorders, 19, 345-359] recommend that these items be reworded to maintain scale sensitivity. The present study examined the reliability and validity of the BFNE-II, a version of the BFNE evaluating revisions of the reverse-worded items in a community sample. A unitary model of the BFNE-II resulted in excellent confirmatory factor analysis fit indices. Moderate convergent and discriminant validity were found when BFNE-II items were correlated with additional independent measures of social anxiety [i.e., Social Interaction Anxiety & Social Phobia Scales; Mattick, R. P., & Clarke, J. C. (1998). Development and validation of measures of social phobia scrutiny fear and social interaction anxiety. Behaviour Research and Therapy, 36, 455-470], and fear [i.e., Anxiety Sensitivity Index; Reiss, S., & McNally, R. J. (1985). The expectancy model of fear. In S. Reiss, R. R. Bootzin (Eds.), Theoretical issues in behaviour therapy (pp. 107--121). New York: Academic Press. and the Illness/Injury Sensitivity Index; Carleton, R. N., Park, I., & Asmundson, G. J. G. (in press-b). The Illness/Injury Sensitivity Index: an examination of construct validity. Depression & Anxiety). These findings support the utility of the revised items and the validity of the BFNE-II as a measure of the fear of negative evaluation. Implications and future research directions are discussed.

Adolescent↗

Daily negative interactions and mood among patients and partners dealing with multiple sclerosis (MS): the moderating effects of emotional support.

Negative interactions with intimate partners may have adverse consequences for well-being, especially for individuals dealing with chronic illness. However, it is not clear whether negative interactions affect both dimensions of positive and negative well-being and factors that may moderate this effect have not been well-described. The aim of the present study was to examine the association between daily received negative responses from the partner and end-of-day positive and negative mood in patients with multiple sclerosis (MS) and their intimate partners. Further, the moderating role of receiving emotional support from the partner on the same day was examined. Sixty-one MS patients and their intimate partners were approached via one MS centre and the neurology department of one hospital in the Netherlands and completed computerized diaries for 14 days. Both partners filled out diaries at the end of each day, recording received negative responses, emotional support and end-of-day positive and negative mood. In line with a domain specific model, patients or partners who reported receiving negative responses on a day had higher end-of-day negative mood, whereas received negative responses were unrelated to end-of-day positive mood. Further, for both patients and partners, the adverse effect of received negative responses on end-of day mood was moderated by receiving emotional support on the same day.

Adult↗

The negative predictive value of spiral computed tomography for the diagnosis of pulmonary embolism in patients with nondiagnostic ventilation-perfusion scans.

BACKGROUND: There is no noninvasive method to rule out pulmonary embolism when the clinical suspicion for pulmonary embolism is high. We did a prospective observational study to determine the negative predictive value of spiral computed tomography (CT) in this situation. METHODS: We performed spiral CT scans of the thorax in consecutive patients with high clinical suspicion of pulmonary embolism with intermediate or low probability ventilation-perfusion scans. Patients with negative or indeterminate spiral CT results had conventional angiography at the discretion of the attending physician. Only patients with positive spiral CT results or positive conventional angiograms were treated. All patients were observed for 6 months for evidence of venous thromboembolic disease. Clinical outcome without treatment or the results of conventional angiography were used as reference standards. False-negative results were defined as a negative spiral CT with a positive conventional angiogram or any diagnosis of venous thromboembolism within 6 months. RESULTS: Among the 103 patients who were studied, spiral CT scans were positive in 22 patients, indeterminate in 10 patients, and negative in 71 patients. Twenty-seven (26%) patients had pulmonary embolism by clinical outcome, including 3 of the 71 patients with negative spiral CT scans and 2 of the 10 patients with indeterminate scans. A negative spiral CT result had a likelihood ratio of 0.12 (95% confidence interval [CI]: 0.04 to 0.35) with a negative predictive value of 96% (95% CI: 88% to 99%). Using conventional angiography only as the reference standard, a negative spiral CT result had a likelihood ratio of 0.08 (95% CI: 0.02 to 0.31) and a negative predictive value of 93% (95% CI: 77% to 98%). CONCLUSIONS: Spiral CT has a high negative predictive value for pulmonary embolism and may replace conventional angiography in the workup of pulmonary embolism. Patients with indeterminate spiral CT results should be considered for conventional angiography.

Adult↗

Negative symptoms and regional cerebral blood flow in patients with schizophrenia: a single photon emission computed tomography study.

There have been few functional imaging studies of negative symptoms in schizophrenia during the resting state, particularly in Asian patients with schizophrenia. The aim of this study was to evaluate the relationship between regional cerebral flood flow (rCBF) and negative symptoms, and to discuss the association between severity and subgroups of negative symptoms and rCBF. Sixteen patients with chronic schizophrenia were evaluated for negative symptoms using the Scale for the Assessment of Negative Symptoms (SANS), and brain single photon emission computed tomography (SPECT) imaging to assess rCBF during the resting state. Results were assessed using Spearman's correlation analysis. Total SANS scores were significantly negatively correlated with bilateral hypofrontality, especially in the left orbital frontal and bilateral superior frontal areas. Subscores for attention were significantly negatively correlated with the left lower frontal-temporal area and the right cerebellum. Subscores for anhedonia had a negative correlation with the right hemisphere. Subscores for affect were negatively correlated with rCBF in the bilateral prefrontal and bilateral superior frontal areas. There were no associations between rCBF and SANS in alogia and avolition. These results support the notion that frontal lobe dysfunction in schizophrenia is associated with negative symptoms. The left anterior hemisphere may play an important role in attention deficit. These relationships between negative symptoms and neuroanatomy require further clarification.

Adult↗

Estrogen receptor-negative breast carcinomas: a review of morphology and immunophenotypical analysis.

Estrogen receptor (ER)-negative breast cancers are a group of tumors with poor prognosis and fewer cancer prevention and treatment strategies compared to ER-positive tumors. The aim of this study was to assess the morphological characteristics and immunohistochemical profile of ER-negative tumors and thus to understand the biological behavior and unique nature. In total, 291 consecutive ER-negative cases available from our primary breast cancer series were examined. Hematoxylin- and eosin-stained sections of all the cases were studied for several morphological parameters and their immunophenotype profile. These findings were correlated with patient and tumor characteristics and survival data. ER-negative tumors constituted 30% of the primary operable breast cancer series. The majority of tumors were grade 3 (94%) and the commonest histological types were ductal/no specific type (85%), and atypical medullary carcinoma (8%). High-grade comedo-type necrosis, lymphoid stroma, central necrosis/fibrosis and pushing margins were the most common morphological features. The presence of a pushing margin showed a significant relation to androgen receptor negativity, absence of epidermal growth factor receptor expression and negative lymph nodes. Lymphoid stroma and comedo-necrosis correlated with higher tumor grade. ER-negative breast cancers are a distinct group of tumors with several common morphological features. Grade 3 histology, pushing margin, lymphoid stroma, comedo-type necrosis and central fibrosis/necrosis are the dominant morphological findings. The presence of a pushing margin appears to have a significant correlation with negative lymph node status. ER-negative tumors show a higher expression of p53, CerbB2 and epidermal growth factor receptor compared to ER-positive breast cancer. These unique features support the concept that ER-negative tumors are a morphologically and phenotypically distinct entity and provide a rationale for the study and use of newer promising agents in the treatment of ER-negative breast cancer.

Actins↗

The routine use of Rh-negative reagent red cells for the identification of anti-D and the detection of non-D red cell antibodies.

BACKGROUND: Before 1987, fewer than 50 patients per year at the authors' laboratory had a positive antibody detection test due to antepartum Rhesus immunoprophylaxis. However, after 1987, a marked increase was observed in the number of patients who had received Rh immune globulin (RhIG) during pregnancy as part of routine antepartum Rh immunoprophylaxis. In anticipation that an increased use of RhIG during pregnancy would increase the number of patients in whom anti-D was detected by this laboratory, a protocol was developed to abbreviate the process required to identify anti-D. Although this protocol was adopted primarily to address an anticipated increase in antenatal RhIG usage in women, it was also applied to alloimmunized Rh-negative males. STUDY DESIGN AND METHODS: When an Rh-negative patient (male or female) had a reactive screening test for unexpected antibodies and met certain other criteria, the patient's serum was tested with a three-vial set of Rh-negative reagent red cells (Rh-negative screening RBCs), instead of with panels of typed RBCs (panel RBCs), for the identification of anti-D or the detection of non-D antibodies. If the serum under test did not agglutinate or hemolyze Rh-negative screening RBCs, anti-D was identified and no further testing was performed. If the serum agglutinated or hemolyzed Rh-negative screening RBCs, conventional testing with panel RBCs was done to determine the antibody specificity. RESULTS: Rh-negative patients (n = 1174) who had reactive screening tests for unexpected antibodies were tested with Rh-negative screening RBCs; 1079 were found to have anti-D as a single antibody. Seven of these patients subsequently developed a non-D alloantibody, after transfusion or pregnancy, and one patient had anti-C that escaped detection at the time of initial testing with Rh-negative RBCs (a false-negative result). Ninety-two patients had anti-D in combination with a non-D antibody, and three patients had a non-D antibody but not anti-D. Use of the anti-D identification protocol actually reduced the laboratory workload by 176 College of American Pathologists workload units per month, in spite of a marked increase in the number of patients in whom anti-D was detected. No hemolytic transfusion reaction was attributed to the abbreviation of anti-D identification. CONCLUSION: The identification of anti-D may be abbreviated without jeopardizing patient safety. Such a protocol can reduce laboratory workload and might be particularly appealing to health care facilities that perform antibody detection testing on large numbers of Rh-negative pregnant women, especially if antepartum RhIG is administered routinely.

Erythrocytes↗

Prevalence and prognosis of electrocardiographic left ventricular hypertrophy, ST segment depression and negative T-wave; the Copenhagen City Heart Study.

AIMS: To evaluate the prevalence and the independent prognosis of electrocardiographic left ventricular hypertrophy by voltage only, ST depression and negative T wave, isolated negative T wave and left ventricular hypertrophy plus ST depression and negative T wave for cardiac morbidity and mortality, without known ischaemic heart disease at baseline. METHODS AND RESULTS: Follow-up data from the Copenhagen City Heart Study were used. Subjects were 5243 men and 6391 women, age range 25-74 years. End-points were (1) myocardial infarction, (2) ischaemic heart disease and (3) cardiovascular disease mortality. Relative risk was age- and sex-adjusted, and multivariately adjusted for known cardiovascular risk factors. During 7 years follow-up, left ventricular hypertrophy plus ST depression and negative T wave had an age-adjusted relative risk of 3.78 (95% confidence interval 2.29-6.25) for myocardial infarction, 4.27 (2.95-6.16) for ischaemic heart disease and 3.75 (2.41-5.85) for cardiovascular disease. A negative T wave, ST depression and negative T wave changes, and left ventricular hypertrophy with negative T wave also carry independent prognostic information for myocardial infarction, ischaemic heart disease and cardiovascular disease. CONCLUSIONS: Electrocardiographic left ventricular hypertrophy with ST depression and negative T wave changes are the electrocardiographic abnormalities with the greatest prognostic information for future cardiac events. Electrocardiographic negative T waves, ST depression and negative T wave abnormalities and left ventricular hypertrophy with negative T waves, also have prognostic information.

Adult↗

Ziprasidone and amisulpride effectively treat negative symptoms of schizophrenia: results of a 12-week, double-blind study.

We compared the efficacy of ziprasidone and amisulpride in the treatment of negative symptoms and overall psychopathology in subjects who had chronic schizophrenia with predominantly negative symptoms. This multicentre, 12-week, double-blind study randomly assigned subjects with predominantly negative-symptom schizophrenia [i.e. Positive and Negative Syndrome Scale (PANSS) Negative Subscale score >or=6 points greater than Positive Subscale score] to ziprasidone (40-80 mg b.i.d.; n=60) or amisulpride (50-100 mg b.i.d.; n=63). The primary efficacy variable was the change from baseline in PANSS Negative Subscale score. Secondary efficacy variables included change in scores for PANSS Total, Global Assessment of Functioning, Brief Psychiatric Rating Scale derived from PANSS Total and Core, Clinical Global Impression (CGI)-Severity and CGI-Improvement. For the change in PANSS Negative Subscale score, a ratio to assess the equivalence of the treatment groups was calculated from the least squares mean changes from baseline, with equivalence claimed if the lower limit of the 95% confidence interval of the ratio exceeded 0.60. Mean daily dose, adjusted for differential numbers of subjects and differential days between visits, was 118.0 mg for ziprasidone and 144.7 mg for amisulpride. Mean PANSS Negative Subscale scores improved over the 12-week treatment period for intent-to-treat subjects, evaluable subjects (subjects with >or=4 weeks of double-blind treatment and no protocol deviations) and completers in both treatment groups. Ziprasidone demonstrated efficacy comparable to amisulpride in improving negative symptoms and global psychopathology. The groups demonstrated comparable improvements in secondary efficacy variables. Both agents were generally well tolerated, with comparably low incidences of movement disorders. In subjects with negative symptom-prominent schizophrenia, ziprasidone in mean daily doses of 118 mg was equivalent to amisulpride in mean daily doses of 148 mg in ameliorating negative symptoms and comparable in improving overall psychopathology and global illness severity.

Adult↗

Helicobacter pylori-negative duodenal ulcers: prevalence, clinical characteristics, and prognosis--results from a randomized trial with 2-year follow-up.

OBJECTIVE: The proportion of Helicobacter pylori-negative duodenal ulcer disease appears to be increasing. Data on clinical outcome and prognosis in this subgroup are lacking. METHODS: Two hundred seventy-six duodenal ulcer patients randomized, irrespective of H. pylori status, to either eradication therapy or maintenance omeprazole (double-blind, double-dummy design) for 1 yr were studied. Patients were followed up for a total of 2 yr, with visits performed every 2 months the first year and every 6 months the following year. Endoscopies for assessment of ulcer relapse were done at 6 and 12 months or in the event of symptomatic relapse. H. pylori status was assessed by culture, immunohistochemistry, and urea breath test at entry, at 6, 12, and 24 months or at failure. The primary endpoint was discontinuation, irrespective of reason. Patients were considered H. pylori negative if all three tests were negative. Patients were considered H. pylori-positive if any of the three diagnostic tests were positive. Study staff were blinded to H. pylori results. RESULTS: Thirty-two (12%) patients were H. pylori negative at entry. There were no differences according to H. pylori status for a number of clinical and demographic characteristics. However, H. pylori-negative patients had a shorter history of ulcer symptoms and were more likely to be NSAID users (19% vs 1%, p < 0.001). Only 28% of the H. pylori-negative patients completed the study, as compared with 40% of H. pylori-positive patients (p = 0.0005). The main reasons for the poorer prognosis in H. pylori-negative patients were relapse of ulcer/ulcer not healed (35% vs 26%) and relapse of severe dyspepsia symptoms without ulcer relapse (16% vs 7%). H. pylori-negative patients randomized to eradication therapy left the study early compared with H. pylori-negative patients randomized to long-term omeprazole therapy. Outcome in omeprazole-treated patients did not differ according to H. pylori status (p = 0.3). CONCLUSIONS: Clinical characteristics in H. pylori-negative and positive duodenal ulcer patients differ little. Clinical outcome over 2 yr is significantly poorer in H. pylori-negative patients, especially if treated empirically with eradication therapy. These results suggest that H. pylori infection should be assessed in all duodenal ulcer patients before treatment is decided.

Adult↗

Role of p53, apoptosis, and cell proliferation in early stage Epstein-Barr virus positive and negative gastric carcinomas.

AIMS: Mechanisms of Epstein-Barr virus (EBV) associated gastric tumour development are incompletely understood. The interrelations between EBV infection, apoptosis, cell proliferation, and the expression of the tumour suppressor gene p53 was investigated in 133 early stage gastric carcinomas. METHODS: Tumour tissue was compared with paired non-tumour tissue. EBV encoded small RNAs (EBERs) determined EBV status. The apoptotic index (AI) was determined by morphology and verified biochemically. p53 and Ki-67 expression (cell proliferation) was assessed using immunohistochemistry. RESULTS: EBV was detected in 14.3% of the cases. Cell proliferation did not differ significantly between EBV positive and negative cancers. However, within both these groups, the p53 positive and negative subsets differed significantly (EBV positive group: 76.8% and 55.3% were p53 positive or negative cancers, respectively; p<0.05; EBV negative group: 65.2% and 51.7% were p53 positive or negative, respectively; p<0.005). The numbers of p53 expressing EBV positive and negative cases were significantly different (57.9% and 82.5%, respectively; p<0.05). Compared with cell proliferation, apoptosis was significantly lower in EBV positive versus negative cancers (AI of 4.36 and 6.50, respectively; p<0.01). The p53 positive and negative subsets also differed significantly in AI (EBV positive group: AI of 5.13 and 3.30 for p53 positive and negative cancers, respectively; p<0.05: EBV negative group: AI of 6.84 and 4.90 for p53 positive and negative cancers, respectively; p<0.05). CONCLUSIONS: These factors probably combine to promote development and progression of early stage gastric carcinomas and, at the same time, ensure the survival of EBV itself.

Adenocarcinoma↗