Retrospective study on timing of resection of hepatocellular adenoma.

BACKGROUND: Hepatocellular adenoma (HCA) is a benign liver tumour that may be complicated by bleeding or malignant transformation. Present guidelines advise cessation of oral contraceptives and surgical resection if the lesion is still larger than 5 cm at 6 months after diagnosis. The aim of this study was to evaluate whether this 6-month interval is sufficient to expect regression of a large HCA to 5 cm or smaller. METHODS: This retrospective cohort study included all patients with an HCA larger than 5 cm diagnosed between 1999 and 2015 with follow-up of at least 6 months. Medical records were reviewed for patient characteristics, clinical presentation, lesion characteristics, management and complications. Differences in characteristics were assessed between patients kept under surveillance and those who underwent treatment for an HCA larger than 5 cm. RESULTS: Some 194 patients were included, of whom 192 were women. Eighty-six patients were kept under surveillance and 108 underwent HCA treatment. Patients in the surveillance group had a significantly higher BMI (P = 0·029), smaller baseline HCA diameter (P < 0·001), more centrally located lesions (P < 0·001) and were more likely to have multiple lesions (P = 0·001) than those in the treatment group. There were no significant differences in sex, age at diagnosis, symptoms, complication rates and HCA subtype distribution. Time-to-event analysis in patients managed conservatively and those still undergoing treatment more than 6 months after diagnosis showed that 69 of 118 HCAs (58·5 per cent) regressed to 5 cm or smaller after a median of 104 (95 per cent c.i. 80-128) weeks. Larger HCAs took longer to regress (P < 0·001). No complications were documented during follow-up. CONCLUSION: This study suggests that a 6-month cut-off point for assessment of regression of HCA larger than 5 cm to no more than 5 cm is too early. As no complications were documented during follow-up, the cut-off point in women with typical, non-ß-catenin-activated HCA could be prolonged to 12 months, irrespective of baseline diameter.

Serum bactericidal antibody assays - The role of complement in infection and immunity.

Complement is an essential component of the immune system and human pathogenic organisms have developed various mechanisms for evading complement mediated serum killing. The "gold standard" for measuring the ability of vaccine-induced antibody to kill Neisseria meningitidis is the serum bactericidal antibody (SBA) assay which measures complement mediated killing via antibody. This assay requires active complement, either intrinsic from the serum being tested or the addition of exogenous complement, either from a human or from another species such as rabbit. For serogroup C, an SBA titre of ≥4 was established as the correlate of protection when using human complement and ≥8 as the threshold when using rabbit complement, based on comparative assay results. Licensure of meningococcal vaccines, including polysaccharide protein conjugate vaccines and serogroup B vaccines has been based on the immune responses measured with the SBA assay, thus on a surrogate of vaccine efficacy. This review examines the use of complement and the SBA assay to assess immunity to meningococcal infection, and provides examples of vaccine trials in different age groups where various assays have been used.

Following a tick bite: double infections by tick-borne encephalitis virus and the spirochete Borrelia and other potential multiple infections.

In Central Europe and large parts of Asia, tick-borne-encephalitis (TBE) and Lyme borreliosis caused by the spirochetal bacterium of the genus Borrelia are among the most common diseases transmitted by the bite of a tick. When in regions with overlapping TBE virus and Borrelia endemicity, a tick bite causes the victim to become ill, it is important that appropriate serological and other laboratory investigations form part of the differential diagnosis. Account must always be taken of the fact that a tick bite may be followed by a double infection with the TBE virus and Borrelia. For this reason, a comprehensive diagnostic work-up aimed at detecting co-infection by both pathogens, even when the tick bite occurs in an endemic region for both pathogens but the initial clinical symptoms suggest an infection with only one of the two pathogens. The present article discusses a number of published cases of a co-infection with TBE virus and Borrelia and other potential multiple infections.

State of the art in aspiration assessment and the idea of a new non invasive predictive test for the risk of aspiration in stroke.

BACKGROUND: Dysphagia is a common but severe complication in acute stroke. New bedside tests are necessary to assess the risk of aspiration and avoid unnecessary alimentary restrictions but they must be completed by evaluated instruments. OBJECTIVE: We evaluated the prognostic validity of the recognition of forms (rf) test related to the assessment by speech and language therapists (SLT). DESIGN: Double blinded screening tests. SETTING: Geriatric department of general hospital. SUBJECTS: 50 patients with acute stroke admitted consecutively. METHODS: All patients were assessed by SLT, mini mental status test, short test for assessing deficits of memory and attention and abilities of daily living-test. The rf-test was performed twice with a two week interval. RESULTS: Assessment by SLT demonstrated aspiration in 29 of 50 patients. 18 patients failed the rf-test, giving a specificity of 90% (positive predictive value 89%), a sensitivity of 55% (negative predictive value 59%). 5 of 7 patients with aspiration pneumonia failed the test. Test-retest-correlation was 0,827. Performance in the rf-test was related significantly to results of the activities of daily living-test. CONCLUSIONS: Bedside tests to exclude aspiration in patients with acute stroke are necessary. No test so far combines high sensitivity with acceptable specificity. Compared to other bedside tests the rf-test has a high specificity while sensitivity is low. On behalf of good predictivity rf-test may be an interesting supplement to swallow tests in case of stroke and seems to be a candidate for more extended studies.

Burden of invasive disease caused by Haemophilus influenzae type b (Hib) in Africa.

More than 10 million children younger than 5 years of age die every year and the majority of them from diseases that can be prevented by vaccines. Invasive infections caused Haemophilus influenzae b are one of the leading causes of infant and childhood pneumonia and meningitis. Hib can effectively been prevented by Hib conjugate vaccine which has been introduced during the 1990s in industrialized countries and has virtually eliminated invasive Hib disease. The poorest countries however, do not yet have implemented this safe and preventive intervention and one reason for this gap is low awareness and poor perception of published data and recently developed combination vaccines enabling effective immunization against five diseases by one vaccine (five in one). This article provides a descriptive analysis of the burden of Hib disease in Africa and shows the importance of implementation of vaccine in the this continent.

Meningococcal disease: a review on available vaccines and vaccines in development.

Meningococcal disease continue to have a major public health impact in many countries. Five major groups of Neisseria meningitidis (A, B, C, Y and W135) are responsible for most meningococcal diseases. Plain polysaccharides vaccines for Neisseria meningitidis groups A, C, Y and W-135 have been in use for approximately 20 years, both to prevent invasive disease in high-risk population and to control disease outbreaks. However, these conventional meningococcal vaccines induce a relatively short-lasting T-cell independent immune response, are not effective in children under two years of age and can induce hyporesponsiveness. New meningococcal group C conjugate vaccines have since been developed, which offer solid advantages over the currently licensed plain polysaccharide vaccines. Tetravalent serogroup A, C, Y and W135 meningococcal vaccines are under development and one has already been licensed. There is still no universal vaccine available against the serogroup B, which is a major cause of invasive disease. This report summarises the different approaches to the development of vaccines against the pathogenic meningococci.

IgG and IgE immune response against the surface glycoprotein gp200 of Saccharomyces cerevisiae in patients with atopic dermatitis.

The heat-stable and soluble glycoprotein gp200 (molecular weight 200 kDa) is part of the cell wall of S. cerevisiae. Recently, an association was shown between IgA and IgG against gp200 and inflammation in Crohn's disease. Gp200 is able to induce a proliferation of human lymphocytes in vitro, together with a natural killer cell associated cytotoxicity. Specific IgE against Saccharomyces cerevisiae (baker's or brewer's yeast) may be detected in approximately 73%, against Candida albicans in 68% of those patients suffering from severe atopic dermatitis. The aim of this study was to elucidate the possible role of an anti-gp200 immune response for the pathogenesis of atopic dermatitis by immunoblot analysis. Anti-gp200 IgE was found in 55% of healthy individuals, in 67% of individuals with atopic predisposition without eczema, in 63% of the patients with mild atopic dermatitis, and in 86% of patients with severe atopic dermatitis, respectively. On the contrary, anti-gp200 IgG could be shown in 55% of healthy individuals, in 89% of individuals with atopic predisposition but without eczema, in 100% of patients with mild atopic dermatitis, and in 79% with severe atopic dermatitis, respectively. No immunoreactivity was found when an extract of Arxula adeninivorans was used as antigen. These results underline the specificity of the immunoblot results with gp200 from Saccharomyces cerevisiae. It can be concluded that occurrence of specific IgE against Saccharomyces cerevisiae cannot be explained by a cross reactivity, e.g., against Candida albicans allergens. Further investigations with the recombinant gp200 will give information on the role of this glycoprotein both in atopic dermatitis and Morbus Crohn.

[Political change in East Germany 1989-90 in the lives of chronic schizophrenic patients]. / Die politische Wende 1989/90 im Erleben chronisch schizophrener Patienten.

Theoretical models suggest a higher vulnerability of chronic schizophrenic patients for critical life events and rapid change of objective living circumstances. On the basis of these models one may hypothesise that the political change in East Germany in 1989/90 was objectively or subjectively distressing to such patients and had a negative impact on their illness. In a retrospective longitudinal study, we investigated patients' assessment of political change, life events that were potentially related to the political changes, impact of the changes on subjective quality of life, and hospitalization rates during five year periods prior to and following the change. 120 patients with chronic schizophrenia in East Berlin and 70 in Chemnitz were examined using quantitative and qualitative methods. Patients reported more individual freedom and better care after 1989. They complained about stress due to loss of employment, financial disadvantages and rising crime rates. Despite the occurrence of potentially change-related life events after 1989, patients stated very little impact of the changes on their illness. Retrospectively, patients in East Berlin reported a significantly better subjective quality of life in 1994 than in 1984. Hospitalization rates did not increase after 1989. The findings are not consistent with the hypothesis and do not suggest that political changes in East Germany in 1989/90 had--subjectively or objectively--a substantial negative effect on the illness of patients with chronic schizophrenia.

Political change and course of schizophrenia in East Germany, 1984-1994.

BACKGROUND: We tested the hypothesis that the political change occurring in East Germany after the fall of the Berlin Wall in November 1989 affected patients with long-term schizophrenia, resulting in more and longer hospitalisations. METHODS: In two samples in East Germany (120 patients in East Berlin, 70 patients in Chemnitz) and in a control group from West Berlin (40 patients), hospitalisations for each month between November 1984 and October 1994 were assessed. Each sample included all schizophrenia patients who were in continuous treatment in the given community mental health centre throughout the full observation period. RESULTS: Hospitalisation indices were not higher after November 1989 than before in any of the groups. CONCLUSIONS: There is no evidence that political change in East Germany negatively affected the course of longterm schizophrenia as assessed by hospitalisations. If consistent medical care is provided, characteristics of the political system may have less impact on the course of schizophrenia than is sometimes assumed.

Prediction of hospitalizations by schizophrenia patients' assessment of treatment: an expanded study.

This study examines whether schizophrenia patients' global assessment of treatment predicts outcome in community care. Eighty-five patients rated the extent to which their treatment was right for them. The outcome measure was assessed by means of a hospitalization index reflecting the duration of full and partial hospitalization within a follow-up period of 24 months. Patients who dropped out (n = 21) assessed their treatment more negatively than those who remained in the care system during follow-up. Patients with no hospitalization (n = 25) expressed a more negative assessment than patients who were hospitalized in the follow-up period at least once (n = 39). In this latter subgroup, however, patients with a more negative assessment had a longer duration of hospitalization during follow-up, and patients' assessment of treatment was the best single predictor of outcome (r = -0.50, P < 0.01). In a multiple regression analysis, patients' assessment of treatment, the number of previous hospitalizations and the hospitalization index in the two years prior to the interview, together, explained approximately half of the variance of outcome (adjusted R2 = 0.46). The findings underline the relevance of asking patients whether treatment is right for them, although the relationship between patients' assessment of treatment and long-term outcome seems more complex than previous studies suggested.

Humoral immune response to a 200-kDa glycoprotein antigen of Saccharomyces cerevisiae is common in man.

According to Heelan et al. patients suffering from Crohn's disease (CD) produce antibodies against a cell wall associated glycoprotein antigen gp200 of the yeast Saccharomyces cerevisiae, while healthy people do not. Here the authors show, that antibodies against this glycoprotein gp200 can also be detected in the sera of healthy humans. The intensity of the antibody titer which is measured by immunoblot experiments is independent from the state of health. The Saccharomyces cerevisiae specific gp200 is a highly glycosylated protein localized not only in the cell wall but also accumulated in the culture medium. Some of the tested sera from CD patients, as well as from healthy adults, also reacted with a 120-kDa glycoprotein which is to be found in preparations containing secreted proteins. Because the binding of antibodies is greatly reduced by periodate treatment of gp200 and by the 120-kDa polypeptide, it is very likely that their carbohydrate moieties are the antigenic determinants against which the specific human antibodies are directed. The human humoral immune response applies only to Saccharomyces cerevisiae antigens, because no analogous immune responses could be detected against antigens derived from the yeast Arxula adeninivorans.

Involuntary admission and posttraumatic stress disorder symptoms in schizophrenia patients.

In a sample of 105 community-care patients suffering from schizophrenia, the relationship between reports of involuntary admission in the past, current posttraumatic stress disorder (PTSD) symptoms, and other aspects of psychopathology was examined. PTSD symptoms were obtained on the PTSD interview, and psychopathology was rated on the Brief Psychiatric Rating Scale (BPRS) and on the Present State Examination (PSE). Fifty-seven percent of the patients reported they had experienced involuntary admissions in the past. The degree of PTSD symptoms was high--51% fulfilled the criteria for a PTSD diagnosis. PTSD symptoms were not correlated with reports of involuntary admissions. They were, however, significantly correlated with the BPRS subscale anxiety/depression, and with PSE subscores for specific and nonspecific neurotic syndromes. Because of an overlap of symptom scores, a diagnosis of PTSD according to DSM criteria appears to be very difficult in schizophrenia patients.

Evidence for secretion of vacuolar alpha-mannosidase, class I chitinase, and class I beta-1,3-glucanase in suspension cultures of tobacco cells.

We have investigated the possibility that vacuolar proteins can be secreted into the medium of cultured cells of Nicotiana tabacum L. Time-course and balance-sheet experiments showed that a large fraction, up to ca. 19%, of vacuolar alpha-mannosidase (EC 3.2.1.24) and vacuolar class I chitinase (EC 3.2.1.14) in suspension cultures accumulated in the medium within one week after subculturing. This effect was most pronounced in media containing 2,4-dichlorophenoxyacetic acid (2,4-D). Under comparable conditions only a small fraction, 1.8-5.1% of the total protein and ca. 1% of malate dehydrogenase (EC 1.1.1.37), which is localized primarily in the mitochondria and cytoplasm, accumulated in the medium. Pulse-chase experiments showed that newly synthesized vacuolar class I isoforms of chitinase and beta-1,3-glucanase (EC 3.2.1.39) were released into the medium. Post-translational processing, but not the release of these proteins, was delayed by the secretion inhibitor brefeldin A. Only forms of the proteins present in the vacuole, i.e. mature chitinase and pro-beta-1,3-glucanase and mature beta-1,3-glucanase, were chased into the medium of tobacco cell-suspension cultures. Our results provide strong evidence that vacuolar alpha-mannosidase, chitinase and beta-1,3-glucanase can be secreted into the medium. They also suggest that secretion of chitinase and beta-1,3-glucanase might be via a novel pathway in which the proteins pass through the vacuolar compartment.

Correct targeting of a vacuolar tobacco chitinase in Saccharomyces cerevisiae--post-translational modifications are dependent on the host strain.

The chitinase gene FB7-1 of Nicotiana tabacum cv. samsun line 5 was expressed in the two Saccharomyces cerevisiae strains, INVSC2 and H4, under the control of the GAL1 promoter from S. cerevisiae and a multicopy plasmid vector. Both yeast strains express the plant gene as enzymatic active proteins. In transformants of the strain INVSC2, 94% of the total plant chitinase is contained inside the cells, probably within the vacuole which has been confirmed by subcellular fractionation as well as immunohistochemical experiments. This retention inside the cells is due to the C-terminally located 7 amino acids long vacuolar targeting peptide of the prochitinase. When this sequence was removed, chitinase was transported into the culture medium. Pulse-chase experiments revealed that during translation in transformants of both yeast strains one chitinase polypeptide can be immunoadsorbed with specific antibodies. In the case of INVSC2-transformants, newly formed chitinase is modified in a 60 min chase to slightly increase its molecular mass, whereas in H4-transformants the molecular mass constantly remained 32 kDa. By Western blot analysis two chitinase corresponding polypeptides of 32 and 37 kDa were accumulated in the culture medium of both transformants carrying the chitinase gene without the vacuolar targeting sequence. The larger one was very likely O-glycosylated. Whereas, both polypepitdes were also detected in cell extracts of the H4-transformant, only the smaller one was found in the INVSC2-transformant. The plant chitinase passed through the endoplasmic reticulum on its way to the vacuole. The N-terminal signal peptide responsible for the uptake into the endoplasmic reticulum is cleaved correctly. However, cleavage of the vacuolar targeting peptide located at the C-terminus, to give the mature chitinase is obviously influenced by the genetic background of the host strain. In INVSC2-transformants chitinase accumulates in its mature form whereas both the polypeptides of H4-transformants retain their vacuolar targeting peptide. Our results demonstrate that in the case of plant class I chitinase, the plant sorting signal is recognized in yeast cells but post-translational modifications are influenced by the host strain.

MR imaging of dislocation of the posterior tibial tendon.

OBJECTIVE: The purpose of this article is to describe the MR imaging appearance of seven cases of posterior tibial tendon dislocation and subluxation. CONCLUSION: Posterior tibial tendon dislocation is a rare but important entity usually related to a previous traumatic event. The clinical diagnosis is often missed because of its rarity. MR imaging provides important clues to the diagnosis and preoperative evaluation of this condition.