Within-host dynamics of antigenic variation.

Genomes of some parasites contain dozens of alternative and highly diverged surface antigens, of which only a single one is expressed in any cell. Individual cells occasionally change expression of their surface antigen, allowing them to escape immune surveillance. These switches appear to occur in a partly random way, creating a diverse set of antigenic variants. In spite of this diversity, the parasitemia develops as a series of outbreaks, in which each outbreak is dominated by relatively few antigenic types. Host-specific immunity eventually clears the dominant antigenic types, and a new outbreak follows from antigenic types that have apparently been present all along at low frequency. This pattern of sequential dominance by different antigenic types remains unexplained. We review the five most prominent theories, which have developed mainly from studies of the protozoans Trypanosoma and Plasmodium, and the bacterial spirochete Borrelia. The most promising theories depend on some combination of mechanisms to create favored connectivity pathways through the matrix of transitions between variants. Favored pathways may arise from biased switches at the molecular level of gene expression or from biases imposed by immune selection. We illustrate the concept of connectivity pathways by reanalysis of data on transitions between variants from Borrelia hermsii.     

The value of a pantaloon cast test in surgical decision making for chronic low back pain patients: a systematic review of the literature supplemented with a prospective cohort study

The results of lumbar fusion in chronic low back pain (LBP) patients vary considerably, and there is a need for proper patient selection. Lumbosacral orthoses have been widely used to predict outcome, however, with little scientific support. The aim of the present study was to determine the value of a pantaloon cast test in selecting chronic LBP patients for lumbar fusion or conservative management. First, a systematic review of the literature was carried out in which two independent reviewers identified studies in Medline, Cochrane and Current Contents databases. Three papers met the selection criteria. In the only study with a control group, a significantly better outcome after fusion compared to conservative treatment was found in patients who reported significant pain relief while in a cast (i.e. a positive cast test). The results of lumbar fusion, however, were not significantly different for patients with a positive and those with a negative cast test. In addition to the review, a clinical cohort study of 257 LBP patients, who had been allocated to either lumbar fusion or conservative management by a temporary external transpedicular fixation trial, was performed. Prior to allocation, all had undergone a pantaloon cast test. Patients with no history of prior spine surgery and with a positive pantaloon cast test had a better outcome after lumbar fusion than those treated conservatively (P = 0.002, χ ² test). In patients with previous spine operations the outcomes were poor and the test was of no value. From the literature and the present patient cohort, it was concluded that only in chronic LBP patients without prior spine surgery, a pantaloon cast test with substantial pain relief suggests a favorable outcome of lumbar fusion compared to conservative management. The test has no value in patients who have had previous spine surgery.     

Nodular lymphocyte-predominant Hodgkin’s lymphoma

Lymphocyte-predominant Hodgkin’s lymphoma (LPHL) differs in histologic and clinical presentation from classical Hodgkin’s lymphoma (cHL). Treatment of LPHL patients using standard Hodgkin’s lymphoma protocols leads to complete remission in more than 95% of patients. Survival and freedom from treatment failure are substantially worse in advanced-stage patients than for early-stage patients. Thus, patients in advanced stages and those in early stages with unfavorable risk factors should be treated similar to those with cHL. In contrast, patients with early-stage LPHL without risk factors might be sufficiently treated with reduced-intensity programs having less severe adverse effects. As a result, treatment of early LPHL is rather heterogeneous, including radiotherapy using extended-fleld technique, involved-fleld radiotherapy (IF-RT), combined-modality treatment, and, more recently, monoclonal antibodies. Watch-and-wait strategy plays an important role in pediatric oncology, to avoid adverse effects associated with therapy. IF-RT seems to be emerging as a treatment of choice for patients with stage IA LPHL; most larger study groups, such as the German Hodgkin Study Group and the European Organisation for Research and Treatment of Cancer, have adopted IF-RT as the treatment of choice for these patients.     

Pre-eclampsia is associated with sleep-disordered breathing and endothelial dysfunction.

Pre-eclamptic toxaemia (PET) may be associated with both endothelial dysfunction (ED) and sleep-disordered breathing (SDB). It was hypothesised that females with PET would demonstrate both SDB and ED, and that a correlation between these two would suggest a potential causative association. A total of 17 females with PET and 25 matched females with uncomplicated pregnancy were studied. They underwent a nocturnal ambulatory sleep study (using Watch_PAT100) and noninvasive evaluation of endothelial function utilising the reactive hyperaemia test (using Endo_PAT 2000). A higher ratio of post- to pre-occlusion pulse-wave amplitude (endothelial function index (EFI)) indicated better endothelial function. Females with PET had a significantly higher respiratory disturbance index (RDI) and lower EFI than controls (18.4+/-8.4 versus 8.3+/-1.3.h(-1), and 1.5+/-0.1 versus 1.8+/-0.1, respectively). Blood pressure significantly correlated with RDI and with EFI. EFI tended to correlate with RDI. In conclusion, these results suggest that both sleep-disordered breathing and endothelial dysfunction are more likely to occur in females with pre-eclamptic toxaemia than in females with uncomplicated pregnancies. The current authors speculate that respiratory disturbances contribute to the functional abnormality of the blood vessels seen in females with pre-eclamptic toxaemia, although causality cannot be determined based on this study.     

Diagnoses of chronic beryllium disease within cohorts of sarcoidosis patients.

An increase in chronic beryllium disease (CBD) has been suggested due to higher industrial use of beryllium alloys. Since occupational CBD is a perfect phenocopy of sarcoidosis, it might be misdiagnosed as sarcoidosis. In the current it was hypothesised that CBD exists in cohorts of sarcoidosis patients. In a prospective case study, sarcoidosis patients were evaluated for potential beryllium exposure. In those patients in whom beryllium exposure was confirmed and beryllium hypersensitivity demonstrated, the diagnosis of sarcoidosis was rejected and corrected to CBD. In 84 patients seen for re-evaluation or making a diagnosis of sarcoidosis, beryllium exposure was recognised and a diagnosis of CBD was made in 34 out of 84 patients. The time lag between clinical diagnosis of sarcoidosis and the final diagnosis of CBD ranged 0-18 yrs (median 3 yrs) and the mean (range) age at time of diagnosis of CBD was 43.9(25-80) yrs. Beryllium-contaminated workplaces causing disease encompassed a wide spectrum of industries and technical trades in which beryllium-exposure is generally not perceived as a health hazard. In conclusion, chronic beryllium disease still belongs to the spectrum of differential diagnoses of granulomatous disorders.     

NT-proBNP reflects right ventricular structure and function in pulmonary hypertension.

The aim of the current study was to investigate whether alterations in N-terminal pro brain natriuretic peptide (NT-proBNP) reflect changes in right ventricular structure and function in pulmonary hypertension patients during treatment. The study consisted of 30 pulmonary hypertension patients; 15 newly diagnosed and 15 on long-term treatment. NT-proBNP, right heart catheterisation and cardiac magnetic resonance imaging measurements were performed, at baseline and follow-up. There were no significant differences between newly diagnosed patients and those on treatment at baseline or follow-up with respect to NT-proBNP, haemodynamics and right ventricular parameters. Relative changes in NT-proBNP during treatment were correlated to the relative changes in right ventricular end-diastolic volume index (r = 0.59), right ventricular mass index (r = 0.62) and right ventricular ejection fraction (r = -0.81). N-terminal pro brain natriuretic peptide measurements reflect changes in magnetic resonance imaging-measured right ventricular structure and function in pulmonary hypertension patients. An increase in N-terminal pro brain natriuretic peptide over time reflects right ventricular dilatation concomitant to hypertrophy and deterioration of systolic function.     

Humoral and Cellular Responses to Influenza Vaccination in Human Recipients Naturally Tolerant to a Kidney Allograft

Rare kidney allograft recipients enjoy unaltered graft function years after interruption of their immunosuppressive treatment. To assess the extent to which this state of 'operational tolerance' (TOL) is specific to the graft and not the result of a global immunodeficiency, we analyzed the response of such patients following influenza vaccination. Hemagglutination inhibition titers and frequency of IFNgamma-secreting T cells were measured before 1 and 3 months after vaccination. The proportion of healthy volunteers (HV) responding to vaccine was significantly higher than that of immunosuppressed (IS) patients. Three 'TOL' patients presented a humoral response similar to that of HV, whereas the two others had a poor response, like the IS recipients. Although the small number of patients does not allow for definitive conclusions to be made, these data suggest that the status of tolerance may be heterogeneous, with some patients with a global immunodeficiency and others with an adapted response to vaccination.     

Anxiety in medically III patients

Anxiety disorders and anxiety symptoms are highly prevalent in the general population and more so in the medically ill. They have a number of negative consequences for these patients and may worsen the outcome of the medical illness and increase health care utilization. In the evaluation of these patients, it is of paramount importance to identify the etiology of the anxiety and, in particular, to differentiate primary from secondary anxiety. Management includes medications (especially benzodiazepines and selective serotonin reuptake inhibitors) and psychotherapy (particularly cognitive-behavioral therapy).