Prospective comparison of noninvasive, bedside ultrasound methods for assessing central venous pressure.

PURPOSE: To prospectively evaluate the accuracy of noninvasive central venous pressure (CVP) assessment by compression ultrasound of a forearm vein (CUS), inferior vena cava (IVC-C) and internal jugular vein collapsibility (IJV-C) compared to invasive CVP measurement (invCVP) as the gold standard. MATERIALS AND METHODS: CUS, IVC-C and IJV-C were performed in a random sequence in 81 consecutive intensive care patients with simultaneous invCVP monitoring. Examiners were blinded to invCVP and previous examinations. RESULTS: Median invCVP was 12.0 mmHg (range 1 - 23). CUS, IVC-C and IJV-C could be obtained in 89 %, 95 % and 100 % of cases, respectively, within a median time of 188 sec [IQR 125; 270], 133 sec [IQR 100; 211] and 60 sec [IQR 50; 109], respectively. The Spearman correlation coefficient between invCVP and CUS, IVC-C, and IJV-C was 0.485 95 %-CI [0.25; 0.65], -0.186 [-0.42; 0.07], and -0.408 [-0.59; -0.18], respectively. The median absolute difference between CUS and invCVP was 3 mmHg [IQR 2; 6.75]. CVP was categorized as low (< 7 mmHg; collapsibility > 0.6), normal (7 - 12 mmHg; collapsibility 0.6 - 0.2) and high (> 12 mmHg; collapsibility < 0.2) as prespecified. The proportions of identical CVP classifications compared to invCVP were 61.4% 95%-CI [49.3%; 72.4%] with CUS, 48.7% [37.4%; 60%] with IVC-C and 51.3% [40.3%; 62.3%] with IJV-C (p > 0.10 for all pair-wise comparisons). CONCLUSION: The overall ability of CUS, IVC-C and IJV-C to assess invCVP was only moderate. CUS seems to be the preferable method if absolute CVP values are needed. IJV-C seems to be the fastest and most easily acquirable method, and thus may be especially valuable in emergency rooms.

CD4+ T-cell-epitope escape mutant virus selected in vivo.

Mutations in viral genomes that affect T-cell-receptor recognition by CD8+ cytotoxic T lymphocytes have been shown to allow viral evasion from immune surveillance during persistent viral infections. Although CD4+ T-helper cells are crucially involved in the maintenance of effective cytotoxic T-lymphocyte and neutralizing-antibody responses, their role in viral clearance and therefore in imposing similar selective pressures on the virus is unclear. We show here that transgenic virus-specific CD4+ Tcells, transferred into mice persistently infected with lymphocytic choriomeningitis virus, select for T-helper epitope mutant viruses that are not recognized. Together with the observed antigenic variation of the same T-helper epitope during polyclonal CD4+ T-cell responses in infected pore-forming protein-deficient C57BL/6 mice, this finding indicates that viral escape from CD4+ T lymphocytes is a possible mechanism of virus persistence.

Impairment of CD4(+) T cell responses during chronic virus infection prevents neutralizing antibody responses against virus escape mutants.

We have shown previously that neutralizing antibodies (nAbs) are important contributors to the long-term immune control of lymphocytic choriomeningitis virus infection, particularly if cytotoxic T cell responses are low or absent. Nevertheless, virus escape from the nAb response due to mutations within the surface glycoprotein gene may subsequently allow the virus to persist. Here we show that most of the antibody-escape viral mutants retain their immunogenicity. We present evidence that the failure of the infected host to mount effective humoral responses against emerging neutralization-escape mutants correlates with the rapid loss of CD4(+) T cell responsiveness during the establishment of viral persistence. Similar mechanisms may contribute to the persistence of some human pathogens such as hepatitis B and C viruses, and human immunodeficiency virus.

[28-year old patient with successfully treated dilatative cardiomyopathy]. / 28-jähriger Patient mit erfolgreich behandelter dilatativer Kardiomyopathie.

A 28-year was admitted with heart failure. His medical history included treatment for hypogonadotropic hypogonadism. Echocardiography showed dilatation of all chambers. Elevated serum ferritin levels and liver biopsy indicated hereditary hemochromatosis. Cardiac iron overload was seen on magnetic resonance imaging. Genetic testing revealed homozygosis for G320 V mutation, confirming the diagnosis of juvenile hemochromatosis. Phlebotomy on a biweekly regimen was started and after twelve months of therapy the patient had normal ferritin values as well as normal ejection fraction on echocardiography.

IgA responses in the intestinal mucosa against pathogenic and non-pathogenic microorganisms.

IgA is the most abundant immunoglobulin produced in mammals; most is secreted as a dimer across mucous membranes. This review discusses the different mechanisms of induction of IgA, and its role in protecting mucosal surfaces against pathogenic and non-pathogenic microorganisms.

Viral escape from the neutralizing antibody response: the lymphocytic choriomeningitis virus model.

In addition to CD8+ cytotoxic T lymphocyte (CTL) responses, neutralizing antibodies contribute substantially to the long-term immune control of noncytopathic viruses, as demonstrated during infection with the lymphocytic choriomeningitis virus (LCMV). The high virus load during the initial phase of an infection and the ability of this RNA virus to spontaneously acquire mutations are important prerequisites for escaping an ongoing immune response. In this context, LCMV escape from the humoral response by single point mutations in neutralizing envelope protein determinants may occur, particularly during conditions of CTL deficiency, leading to virus persistence.

Endocarditis due to Aerococcus urinae: diagnostic tests, fatty acid composition and killing kinetics.

Two cases of Aerococcus urinae endocarditis are reported. The organism is not included in any database of commercial identification systems at this time. Formation of tetrades and positive reactions for leucine arylamidase and beta-glucuronidase pointed strongly to A. urinae. The cellular fatty acid pattern was similar to that of Aerococcus viridans, with predominantly C16:0, C18:1 omega 9c and C18:0; the presence of C18:1 omega 7t differentiated our isolates from A. viridans and can support the diagnosis of A. urinae. Furthermore, susceptibility to penicillin but resistance to cotrimoxazole represents a pattern opposite to that of A. viridans. Minimal inhibition concentrations of gentamicin and netilmicin were < or = 64 mg/l but those of tobramycin were > or = 256 mg/l. Penicillin combined with either gentamicin or netilmicin showed distinct synergy in killing kinetics. These combinations seem to be the appropriate regimen to treat A. urinae endocarditis.

Persistence of lymphocytic choriomeningitis virus at very low levels in immune mice.

Lymphocytic choriomeningitis virus (LCMV), strain WE, is a non-cytopathic RNA virus that is highly adapted to its natural host, the mouse. Acute infection of adult mice leads to generalized virus spread, followed by cytotoxic T lymphocyte-mediated virus clearance below the detection levels of conventional assays within 2-3 weeks. Indirect evidence had suggested that virus or viral antigen might persist in the immune mouse. Here we demonstrate LCMV-WE persistence at low levels after infection with 10(2) or 10(6) plaque-forming units, shown as viral genome, viral antigen, and replicative virus using sensitive in vitro and in vivo assays. The finding that LCMV-WE persists in the face of apparently intact immune responses resembles the situation in some viral (hepatitis B and C, HIV) and bacterial (tuberculosis, leprosy) infections in humans; the results are relevant to the understanding not only of other murine and human persistent viral infections but also of protective immunological memory by "infection immunity."

Viral persistence in vivo through selection of neutralizing antibody-escape variants.

Despite initial virus control by CD8(+) cytotoxic T lymphocytes (CTLs), noncytopathic or variably cytopathic viruses (e.g., hepatitis B and C viruses, HIV) are able to establish persistent infections. The role of neutralizing antibodies (nAbs) in controlling disease progression is unclear. Therefore, the phenomenon of viral evasion from the nAb response and its implications for virus persistence remain controversial. Here we demonstrate nAb-mediated viral clearance in CTL-deficient mice infected with the prototypic noncytopathic lymphocytic choriomeningitis virus (strain WE). During prolonged CTL absence, neutralization-resistant virus mutants were selected in individual mice within 70-90 days. In naive animals infected with these virus variants only low nAb responses were induced, resulting in an increased tendency of virus to persist.