Histamine release in the course of elective conventional cholecystectomy in aged patients: Problems in defining release in relation to specific intraoperative events

The effectiveness of an H₁ ^–+H₂-prophylaxis against perioperative acute pseudoallergic reactions in which histamine is involved, and against postoperative complications the incidence of which may be increased by these reactions, was the central problem of a randomized trial in 162 aged patients during elective conventional cholecystectomy. As main endpoint it was planned to use the systemic histamine release reaction, as it already had been defined for the conscious and anaesthetized human subject. However, it had to be reassessed and redefined for the intraoperative period after improvement of the plasma histamine assay and new findings about stress-induced histamine release and the kinetics of histamine release during certain phases of operation.Intraoperative release is, at present, defined solely as an increase of plasma histamine values after a particular action (phase of operation). It includes criteria concerning plasma histamine changes either in comparison to the base value before surgery or to the preceding value before the last surgical action. Histamine elevations must exceed the last value by more than 3 standard deviations of the analytical error (i.e. 200% if value <0.25 ng/ml=" and=" 40%=" above).=" basic=" requirements=" for=" the=" histamine=" assay=" (quality=" control),=" correct=" sample=" taking=" and=" appropriate=" preparation=" have=" to=" be=" fulfilled=" over=" the=" whole=" trial=" period.=" when=" these=" criteria=" were=" applied=" to=" the=" 162=" patients=" an=" overall=" incidence=" of=" histamine=" release=" during=" cholecystectomy=" of=" 55.6%=" was=" found=" with=" 9.7–20%=" during=" an=" individual=" phase=" of=" operation.=" the=" data=" of=" this=" study,=" performed=" under=" routine=" conditions,=" with=" a=" sufficient=" number=" of=" patients=" with=" elevated=" risk=" and=" event=" controlled=" plasma=" histamine=" values,=" lead=" to=" a=" better=" understanding=" of=" intraoperative=" histamine=" release,=" its=" incidence=" and=">     

Endosonography (ES) in the diagnosis of recurrent cancer of the rectum.

The ability of endosonography (ES) to detect local recurrence after "curative" surgery for rectal cancer was investigated in 65 patients. Fifteen patients developed local recurrence. All of these 15 patients had ES evidence of recurrence; in four cases recurrence was detected by ES alone. Ten of the 15 patients with local failure underwent reoperation. Four patients were candidates for reoperation for cure. Three patients with radical reoperation belonged to the group in which recurrence was detected by ES alone. ES is able to detect small tumors before there is evidence of recurrence in other available forms of examination.     

New spectral detection and elimination test algorithms of ECG and EOG artefacts in neonatal EEG recordings

New methods for the detection of ECG and EOG artefacts in the EEG are introduced, which can also be used for the evaluation of the quality of the elimination procedure. These algorithms are based on the estimation of the power or coherence spectrum by means of FFT. The advantage of this method is that the EEG spectrum is monitored by the test algorithm. The spectrum will be plotted if no influence of the ECG and EOG can be found. On the other hand, if artefacts are detected the correction of the EEG time series will be carried out and the spectrum of the corrected EEG time series will be plotted after repeated monitoring by the test algorithm.     

Role of apoptosis in basal cell and squamous cell carcinoma formation

Long-term ultraviolet-light (UV) exposure of human skin epidermis is associated with an increased risk for the development of skin cancers, such as melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). UV radiation not only induces DNA damage in epidermal cells, it also interferes with skin homeostasis, which is maintained by a unique distribution pattern of apoptosis-inducing and -preventing molecules. If the DNA damage is not repaired or the damaged cells are not eliminated by apoptosis, the consequence can be cell transformation, uncontrolled proliferation and eventually skin tumor formation. An important "repair" gene is the p53 suppressor gene. Excessive UV exposure can mutate the p53 gene leading to the loss of its repair function and thus apoptosis resistance of the DNA-damaged cell. For BCC formation an additional pathway has been identified. Mutation of genes of the Hedgehog signaling pathway evokes the downregulation of apoptotic genes and upregulation of anti-apoptotic genes preventing the elimination of damaged cells. In addition, BCC and SCC strongly express the apoptosis-inducing Fas-ligand (FasL) which may help the tumor to escape the attack of immune effector cells. Silencing the genes involved in tumor formation by RNA interference might become a promising new approach to treat skin tumors.     

Inhibition of plaque formation, rosette formation and phagocytosis by alpha globulin

The immunosuppressive effect of an alpha globulin fraction isolated from normal human plasma is described.

The administration of this material to rats suppressed both the primary and secondary antibody responses against sheep erythrocytes. Alpha globulin also depressed the ability of mice spleen cells to confer immunity to irradiated isologous recipients.

The in vitro addition of alpha globulin to mouse peritoneal leucocytes (MPL) and whole human blood caused a significant reduction of their phagocytic activity against bacteria.

The mode of action of alpha globulin in relation to its immunosuppressive activity is discussed.

     

White Matter Fiber Tracking Computation Based on Diffusion Tensor Imaging for Clinical Applications

Fiber tracking allows the in vivo reconstruction of human brain white matter fiber trajectories based on magnetic resonance diffusion tensor imaging (MR-DTI), but its application in the clinical routine is still in its infancy. In this study, we present a new software for fiber tracking, developed on top of a general-purpose DICOM (digital imaging and communications in medicine) framework, which can be easily integrated into existing picture archiving and communication system (PACS) of radiological institutions. Images combining anatomical information and the localization of different fiber tract trajectories can be encoded and exported in DICOM and Analyze formats, which are valuable resources in the clinical applications of this method. Fiber tracking was implemented based on existing line propagation algorithms, but it includes a heuristic for fiber crossings in the case of disk-shaped diffusion tensors. We successfully performed fiber tracking on MR-DTI data sets from 26 patients with different types of brain lesions affecting the corticospinal tracts. In all cases, the trajectories of the central spinal tract (pyramidal tract) were reconstructed and could be applied at the planning phase of the surgery as well as in intraoperative neuronavigation.     

Distress and DNA repair in human lymphocytes

This research assessed differences in DNA repair in lymphocytes from high-and low-distressed individuals. A median split on Minnesota Multiphasic Personality Inventory (MMPI) Scale 2 divided 28 newly admitted nonpsychotic psychiatric inpatients into high- and low-distress subgroups. The high-distress subgroup had significantly poorer DNA repair in lymphocytes exposed to X-irradiation than low-distress subjects. We also found that lymphocytes obtained from this psychiatric sample had significantly poorer DNA repair than lymphocytes from nonpsychiatric control subjects when compared 5 hr after X-irradiation. A high level of distress therefore appears to be associated with significant dysfunctional differences at the molecular level which may have important implications for health. These data provide evidence for a direct pathway through which distress could influence the incidence of cancer.This research was funded in part by General Molecular Applications, Inc., the Bremer Foundation, the Samuel J. Roessler Fund, and Comprehensive Cancer Center Core Grant CA-16068-09.     

Linkage exclusion and mutational analysis of the noggin gene in patients with fibrodysplasia ossificans progressiva (FOP)

Fibrodysplasia ossificans progressiva (FOP) is an extremely rare and disabling genetic disorder characterized by congenital malformation of the great toes and by progressive heterotopic endochondral ossification in predictable anatomical patterns. Although elevated levels of bone morphogenetic protein 4 (BMP4) occur in lymphoblastoid cells and in lesional cells of patients with FOP, mutations have not been identified in the BMP4 gene, suggesting that the mutation in FOP may reside in a BMP4-interacting factor or in another component of the BMP4 pathway. A powerful antagonist of BMP4 is the secreted polypeptide noggin. A recent case report described a heterozygous 42-bp deletion in the protein-coding region of the noggin gene in a patient with FOP. In order to determine if noggin mutations are a widespread finding in FOP, we examined 31 families with 1 or more FOP patients. Linkage analysis with an array of highly polymorphic microsatellite markers closely linked to the noggin gene was performed in four classically-affected multigenerational FOP families and excluded linkage of the noggin locus to FOP (the multipoint lod score was -2 or less throughout the entire range of markers). We sequenced the noggin gene in affected members of all four families, as well as in 18 patients with sporadic FOP, and failed to detect any mutations. Single-strand conformation polymorphism (SSCP) analysis of 4 of these patients plus an additional 9 patients also failed to reveal any mutations. Among the samples analyzed by SSCP and DNA sequencing was an independently obtained DNA sample from the identical FOP patient previously described with the 42-bp noggin deletion; no mutation was detected. Examination of the DNA sequences of 20 cloned noggin PCR products, undertaken to evaluate the possibility of a somatic mutation in the noggin gene which could be carried by a small subset of white blood cells, also failed to detect the presence of the reported 42-bp deletion. We conclude that mutations in the coding region of noggin are not associated with FOP.     

Antigenic variation in alkaline deoxyribonuclease induced by three different strains of Epstein-Barr virus

To determine whether biological and/or biochemical variants exist between strains of Epstein-Barr virus (EBV), we superinfected Raji cells with the nontransforming lytic strain of EBV (HR-1), and two isolates that both transform B-lymphocytes and superinfect Raji cells, B95–8, and NPC-EBV. The superinfected cells were assayed for EBV specific DNase. A new electrophoretic form of DNase was observed in cells superinfected with B95-8 EBV as compared to the enzymes induced by the HR-1 and NPC-EBV isolates. There were antigenic differences in the DNase induced by the EBV strains. Since antibody to EBV DNase is a marker for nasopharyngeal carcinoma (NPC), these data may have implications for EBV-associated disease.     

Neurobehavioral phenotype in carriers of the fragile X premutation

There have been contradictory findings in the fragile X (fraX) literature about possible neurocognitive and psychological symptoms due to the fraX premutation (pM). The purpose of the present study was to investigate the relationship between CGG repeat length and neurobehavioral functioning in carriers of the fraX pM. Eighty‐five female carriers of the pM with allele sizes ranging from 59–166 were administered a comprehensive IQ test (WAIS‐III) and completed a questionnaire designed to measure psychopathology (Symptom Checklist (SCL)‐90‐R). No relationship between allele size and cognition was identified. A significant negative relationship between allele size and age was found, as well as a positive relationship between allele size and depression. Follow‐up analyses separating small and large allele sizes (below and above 100 CGG repeats) indicated that individuals with larger allele sizes scored significantly higher on the Interpersonal Sensitivity and Depression subscales of the SCL‐90‐R. Despite the limitation of few individuals with high CGG repeat lengths, our findings suggest that females with larger premutated alleles (≥ 100 repeats) display some clinical manifestations of fraX syndrome. © 2001 Wiley‐Liss, Inc.