DELETION OF HAPTEN-BINDING CELLS BY A HIGHLY RADIOACTIVE 125I CONJUGATE

Exposure of normal mouse spleen cells in vitro to highly ¹²⁵I-labeled dinitrophenyl (DNP)-protein carrier conjugates specifically inactivated cells able to mount an immune response to that hapten after in vivo challenge. The deletion was hapten specific and independent of the radioactive carrier to which the hapten was bound. DNP-binding cells were inactivated by radioactivity that was not part of the hapten, but was solely confined to the carrier moiety. The deletion of the anti-DNP response lasted 2–3 wk and could be specifically inhibited.     

Coagulopathy following major liver resection: the effect of rBPI21 and the role of decreased synthesis of regulating proteins by the liver

This prospective study investigated the role of reduced hepatic synthesis of regulating proteins in coagulopathy after partial hepatectomy (PH) compared with major abdominal surgery (MAS) without involvement of the liver. Furthermore, we studied the effect of rBPI21, an endotoxin-neutralizing agent, on coagulopathy after PH was studied. Compared with MAS, PH resulted in significantly elevated levels of thrombin-antithrombin-III and plasmin-alpha2-antiplasmin complexes. Levels of antithrombin-3, alpha2-antiplasmin, fibrinogen, plasminogen, alpha2-macroglobulin (alpha2-M), and C1-inhibitor remained lower following PH. Treatment with rBPI21 led to significantly lower levels of tissue-type plasminogen activator (t-PA). Post-operative disseminated intravascular coagulation (DIC) was associated with significantly higher bilirubin and t-PA plasma levels and significantly lower levels of alpha2-M. This study indicates that PH induced hepatic failure results in decreased synthesis of hepatic regulating plasma proteins and subsequent activation of coagulation and fibrinolysis. Prevention of t-PA release by rBPI21 may have important clinical implications. Decreased availability of alpha2-M may be a factor in post-operative DIC.     

Treatment of compulsive behaviour in eating disorders with intermittent ketamine infusions

We have previously shown that eating disorders are a compulsive behaviour disease, characterized by frequent recall of anorexic thoughts. Evidence suggests that memory is a neocortical neuronal network, excitation of which involves the hippocampus, with recall occurring by re-excitement of the same specific network. Excitement of the hippocampus by glutamate-NMDA receptors, leading to long-term potentiation (LTP), can be blocked by ketamine. Continuous block of LTP prevents new memory formation but does not affect previous memories. Opioid antagonists prevent loss of consciousness with ketamine but do not prevent the block of LTP. We used infusions of 20 mg per hour ketamine for 10 h with 20 mg twice daily nalmefene as opioid antagonist to treat 15 patients with a long history of eating disorder, all of whom were chronic and resistant to several other forms of treatment. Nine (responders) showed prolonged remission when treated with two to nine ketamine infusions at intervals of 5 days to 3 weeks. Clinical response was associated with a significant decrease in Compulsion score: before ketamine, mean +/- SE was 44.0 +/- 2.5; after ketamine, 27.0 +/- 3.5 (t test, p = 0.0016). In six patients (non-responders) the score was: before ketamine, 42.8 +/- 3.7; after ketamine, 44.8 +/- 3.1. There was no significant response to at least five ketamine treatments, perhaps because the compulsive drive was re-established too soon after the infusion, or because the dose of opioid antagonist, nalmefene, was too low.      

Suppression of in vitro antibody response by a serum factor (SAA) in experimentally induced amyloidosis

Serum from CBA/J mice made amyloidotic by chronic casein injections has been shown to suppress in vitro antibody response to SRBC. Similar suppression was also found with normal mouse serum but to a much lesser degree. This suppressive activity of both amyloidotic serum and normal serum was removed by absorption of the sera with antiserum to protein AA, the major constituent of casein-induced (secondary) amyloid fibrils. This antiserum to the amyloid fibril protein AA (mol wt 8,400 daltons) detects an immunologically cross-reacting serum alpha globulin (SAA) (mol wt approx. 100,000). It is postulated that the serum factor (SAA) is a regulator of antibody response and may be present in elevated amounts as the result of chronic antigenic stimulation.     

Direct identification of chlamydiae from clinical samples using a DNA microarray assay: a validation study

While DNA microarrays have become a widely accepted tool for mRNA expression monitoring, their use in rapid diagnosis of bacterial and viral pathogens is only emerging. So far, insufficient sensitivity and high costs have been the major limiting factors preventing more widespread use of microarray platforms in direct testing of clinical samples. In the present study, a total of 339 samples, among them 293 clinical specimens from animals and humans, were examined by the ArrayTube (AT) DNA microarray assay to detect chlamydial DNA and identify the species of Chlamydia and Chlamydophila involved. Samples included nasal and conjunctival swabs, formalin-fixed, paraffin-embedded and fresh organ tissue, milk, feces and cell culture. Notably, the AT test was shown to detect mixed infections in clinical samples. The calculated median sensitivity of 0.81 over the entire panel of clinical samples was comparable to conventional 16S PCR, but slightly lower than real-time PCR and other PCR assays. However, when a panel of long-time stored swab samples was excluded from the calculation, the sensitivity was clearly higher (0.87) and equivalent to that of real-time PCR. Altogether, the data demonstrate the suitability of this DNA microarray assay for routine diagnosis.     

How body position changes visual vertical perception after unilateral vestibular loss

Visual vertical perception, posture and equilibrium are impaired in patients with a unilateral vestibular loss. The present study was designed to investigate whether body position (standing upright, sitting on a chair and lying supine) influences the visual vertical perception in Menière's patients tested before and after a unilateral vestibular neurotomy. Data were compared with sex- and age-matched healthy participants. During the first postoperative month the body position strongly influences the visual vertical perception. The ipsilesional deviation of the visual vertical judgment gradually increased from standing upright to sitting and to lying supine. The present data indicate that visual vertical perception improves when postural control is more demanding. This suggests that postural balance is a key reference for vertical perception, at least up to one month after vestibular loss.     

Sentinel Lymph Node Mapping in Colon Cancer: Current Status

Background The primary role of sentinel lymph node (SLN) mapping in colon cancer is to increase the accuracy of nodal staging by identifying those lymph nodes with the greatest potential for harbouring metastatic disease. Ultrastaging techniques aim to identify the otherwise undetected metastases. Until now, no consensus exists as to the most optimal procedure in patients with colon cancer. Methods A systematic literature search on the value of different SLN mapping techniques in patients with colon cancer was performed using the electronic search engine PubMed. Prospective studies published before 1 December 2005 were included and further articles were selected by cross-referencing. The results of different techniques using either blue dye or radiocolloid, were investigated. Results The literature search yielded 17 relevant articles. SLN mapping using blue dye was described in 15 studies. Two studies reported the results of SLN mapping using a combination of blue dye and radiocolloid. The reported results on identification rate varied between 71 and 100%. Accuracy rates were between 78 and 100%, sensitivity rates between 25 and 100% and true upstaging rates between 0 and 26%. The results were not affected by the addition of radiocolloid to blue dye. Conclusions Sentinel lymph node mapping in patients with colon cancer remains an experimental procedure with varying results. Further evaluation may lead to a standardized technique that offers the potential for significant upstaging of stage II patients. This may have important implications as to tailor adjuvant chemotherapeutic regimens in these patients. Robbert J. de Haas and Dennis A. Wicherts have contributed equally and are mentioned alphabetically.