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=">     

The clinical and biological signs of histamine release during induction of anaesthesia and preparation of the surgical patient: A farewell party for the classical manifestations of anaphylaxis

The clinical manifestations of histamine release and their clinical relevance are still matter of considerable debate among anaesthesiologists whereas surgeons have no opinion at all. In a series of six clinical-experimental trials a gold standard for histamine release was established, the term histamine release reaction was determined, and a combination of clinical predictors was created for assessing the effectiveness of a prophylaxis with histamine H₁+H₂-antagonists.After the construction of the gold standard elevated plasma histamine, in the first three trials the experimental validation, the selection of standard variables for a clinical test and the validation with authentic histamine was accomplished. In three further trials this test was applied to several histamine releasers which have been commonly used for induction of anaesthesia and preparation of a surgical patient, namely, the hypnotic propanidid, the muscle relaxant atracurium, and the plasma substitute Haemaccel. In these trials, H₁+H₂-sensitive variables were also selected for a diagnostic classification of histamine release reactions.     

The immunofluorescence-microscopical evidence of insulin and glucagon in transplantated isolated Langerhans' islets in diabetic rats and dogs (author's transl)]

With the histochemical immunofluorescence technique were demonstrated the insulin and glucagon in the transplantated isolated Langerhans' islets in the liver at diabetic rats and dogs. Further on were tested the diabetic metabolic level with aid of clinico-chemical methods during the period of investigation (blood glucose, serum insulin, glucose tolerance test). It was found that after transplantation, 1 year by the rats and more than 8 weeks by the dogs, is existing a normoglycemic level. In the transplanted islets were seen a good immunofluorescence of insulin in the B cells and the glucagon in the A cells in all investigated stages.     

Changed visuomotor transformations during and after prolonged microgravity

A series of step-tracking experiments was conducted before, during, and after a 3-week space mission to assess the effects of prolonged microgravity on a non-postural motor-control task. In- and post-flight accuracy was affected only marginally. However, kinematic analyses revealed a considerable change in the underlying movement dynamics: too-small force and, thus, too-low velocity in the first part of the movements was mainly compensated by lengthening the deceleration phase of the primary movement, so that accuracy was regained at its end. The observed in-flight decrements in peak velocity and peak acceleration point to an underestimation of mass, in agreement with the re-interpretation hypothesis of Bock et. al. Post-flight no reversals of the in-flight changes (negative aftereffects) were found. Instead, there was a general slowing down, which could be due to post-flight physical exhaustion.     

Evidence for reduced traumatization during laparoscopic versus conventional cholecystectomy: Different changes in histamine levels related to special phases of operation

The role of histamine in injury due to trauma or surgical treatment is more than doubtful after more than 70 years of investigation. A comparison of histamine released during conventional versus minimal invasive surgery seems especially useful to elucidate the role of histamine in such important events of the daily clinical life.Histamine is released during conventional cholecystectomy in patients of high age, a special group of risk for perioperative morbidity and mortality. In animal experiments, it was shown that this histamine release is due to technical differences between the two types of operation. Hence histamine release seems to be a suitable parameter for the stimulus-induced approach to stress and trauma. Histamine is localized in high concentrations especially in abdominal tissues. After its release it may cause direct actions at a susceptible myocardium, pulmonary parenchyma or gastrointestinal mucosa. However, histamine release is also a proxy variable for mast cell irritation, stimulation and mediator release. This should not be forgotten when the role of histamine is discussed in shock, ARDS, DIC and other clinically relevant or even life-threatening events in routine surgical care.     

Localization of corticotropin-releasing activity in the rat hypothalamus

Hypothalamic nuclei were removed from frozen sections of rat brain and examined for their corticotropin-releasing activity. The highest concentration was measured in the median eminence. In addition there was significantly more activity detected in the nuclei paraventricularis, supraopticus, suprachiasmaticus and arcuatus than in the other nuclei.     

Infection of marmosets with parainfluenza virus types 1 and 3.

Infection of wild marmosets (Saguinus mystax) with strains of parainfluenza virus types 1 and 3 resulted in acute respiratory infection. Virus replication in the upper respiratory tract was of a degree similar to that seen in children acutely infected with parainfluenza viruses. Serum antibody developed with both virus types; however, local secretory antibody was not detectable. The infection was transmissible to susceptible animals up to 3 days inoculation of the primary animal.     

Fiber optic probe for polarized reflectance spectroscopy in vivo: design and performance

We present the design and construction of a fiber optic probe for elastic light scattering spectroscopy in vivo with polarized excitation and polarization sensitive detection. The performance of the fiber probe is evaluated using a suspension of polystyrene spheres placed atop a diffusely scattering substrate, and it demonstrates that the size-dependent characteristics of the scatterers can be extracted in the presence of a highly diffusely scattering background using a linear combination of forward and backward Mie scattering components of the scatterers. Subsequently, Mie theory calculations are performed over a broad range of diagnostically relevant parameters of nuclei-mean diameter, size distribution, and relative refractive index-to understand how the polarized reflectance measurements with the fiber probe can be used to extract morphological information about epithelial tissue. Finally, the feasibility of in vivo measurements with the fiber optic based polarization sensitive light scattering spectroscopy is demonstrated.     

T-cell-activation inhibitors in rheumatoid arthritis

As rheumatoid arthritis (RA) is a chronic inflammatory disabling disease and a cure is not available, optimisation of therapeutic strategies is mandatory. Within recent years many new details of the inflammatory cascade(s) have been elaborated, leading to new therapeutic options such as neutralisation of tumour necrosis factor-alpha (TNFalpha). T-cell inhibition is another new approach to the treatment of RA. However, it is important to note two points: first, the role of T lymphocytes in the initiation and/or perpetuation of RA is still debated controversially. Second, there are few truly T-cell-specific agents that have proven to be effective and are established in the treatment of inflammatory disorders. Leflunomide may be considered one such agent; another in development is the fusion protein CTLA4-Ig. From a clinical perspective, studies demonstrating efficacy of these agents might represent the strongest support for a role of T cells in RA. In addition to leflunomide and CTLA4-Ig, therapeutic agents with activity against T cells, including anti-CD4 antibodies, cyclosporin, tacrolimus and T-cell receptor (TCR)-Vbeta-chain vaccination strategies, have been studied in patients with RA. Combination therapies including any of these T-cell-activation inhibitors with non-T-cell-specific agents such as methotrexate, antimalarials or anti-TNFalpha biologicals may prove the most effective strategies in controlling this complex disease.     

Histamine release during induction of anaesthesia and preparation for operation in patients undergoing general surgery: Incidence and clinically severe cases

Histamine release events were shown in a prospective randomized controlled trial in patients undergoing elective general surgery with an extraordinarily high incidence: 73 per cent. This high incidence was explained by several factors: — the sample size which was much greater than in previous studies — the improved plasma histamine assay — the precise definition of histamine release in clinical conditions and its measurement at the top of Bateman functions — the standardized induction of anaesthesia and preparation of the surgical patient — and finally the considerable number of cancer patients since more than 60% of the reactions >5 ng/ml occurred in this group which comprised only 20% of the study population.

Two cases of life-threatening anaphylactoid reactions occurred in this trial corresponding to an incidence of 1 per cent. This was — again — very high compared to previous epidemiological studies. Both cases were again cancer patients and occurred in the placebo group — information given by the external study advisory group for further treatment of the individual patient.

The data on the high incidence of histamine release including the high incidence of life-threatening reactions favourrationally a preoperative H₁ ⁻+H₂-prophylaxis with the drugs used in this study: dimetindene and cimetidine. The question of the incidence was one of the unsettled problems which led to this trial. Analysis of the first 180 patients already answered this question more than we had ever expected.