In vitro and in vivo studies of radiographic contrast media-induced histamine release in pigs.

Routine clinical use of radiographic contrast media (RCM) causes adverse reactions in some patients. To elucidate the mechanisms of these reactions both in vitro and in vivo studies are necessary. In this study, RCM-induced histamine release from isolated mast cells was compared with the in vivo release of histamine and cardiovascular symptoms using a porcine model. The 2 non-ionic preparations examined (Solutrast and Ultravist) released little or no histamine from the 4 cell types tested (porcine pulmonary, cardiac, hepatic, and renal mast cells). The 4 ionic preparations (Angiographin, Hexabrix Rayvist, and Telebrix) caused histamine release from most of the cell suspensions. In almost all cases, the cardiac mast cells were the most sensitive followed by the hepatic mast cells. All 4 RCM tested in vivo produced elevated plasma histamine levels in some animals. The highest incidence was observed using the ionic, high osmolal Rayvist (6 of 12 animals), followed by the non-ionic RCM with the lowest osmolality Ultravist (4 of 12 animals). In vivo, mechanisms in addition to direct histamine release may also be involved in RCM-induced adverse reactions, since low osmolal, non-ionic RCM can cause elevated plasma histamine levels without in vitro release. The susceptibility of cardiac mast cells to RCM-induced histamine release suggests that patients undergoing e.g. coronary angiography may be especially at risk for an adverse reaction.     

Apoprotein AII in acute pancreatitis: intriguing improvement in the prediction of fatal outcome

In spite of significant advances in the past decade, assessing of severe prognosis in acute pancreatitis remains an improvable problem. Actually the standardized means are clinical, multiple laboratory and peritoneal lavage. In a series of 20 subsequent cases of acute pancreatitis with a lethality of 30%, apolipoprotein AII has proven to be a predictor of fatal outcome with a sensitivity in the range of all other methods together. Competitive replacement of Apo AII by serum amyloid like substance A as an indicator for the amount of necrosis would explain this relation. Whether this suggestion can be confirmed by ongoing work or not, apolipoprotein AII merits attention in this context.     

The Dodo Bird: Less a Verdict Than an Opportunity

I contend that although the Luborsky et al. findings on the Dodo bird verdict are noteworthy, the methodology on which they are based is significantly delimited. Amplifying Luborsky et al.'s moderate recognition of that delimitation, I propose a qualitative complement to the extant research. I call this complement "amalgamated" qualitative research and propose that it will deepen, clarify, and contextualize Luborsky et al.'s enigmatic findings. Until this amalgam is implemented, therapy research will be relegated to impressions rather than fine-grained illuminations.     

Die proximale Femurfraktur des älteren Patienten

In a retrospective study, 1.173 fractures of the proximal femur, which had been treated surgically, were analysed in two periods from 1975 to 1991 and from 1992 to 2000. The influence on mortality of preoperative risk factors and primary treatment with total hip replacement (THR), even in cases of pertrochanteric fractures, was analysed by stepwise logistic regression. In the later period, mortality within 90 days was 13.1%, and within 1 year 22.2%. Rejection of hemiendoprosthesis in high-risk patients with intracapsular fractures increased the mortality rate from 6.3% to 11.8%. The introduction of dynamic hip screws instead of Ender nails led to a reduction of mortality from 16.5 to 7.1%. Higher mortality after THR (27.6%) compared to osteosynthesis (15.5%) in pertrochanteric femur and lateral neck fractures was due to higher age and increased risk factors. Although the influence of some risk factors could be reduced, age, sex and morbidity influenced the outcome more than surgical treatment. THP, even after pertrochanteric fractures, is reasonable if it guarantees a quick and enduring mobilisation of the patient. Bicentric bipolar prostheses are recommended for high risk patients.     

The role of complement, C5a and its receptors in sepsis and multiorgan dysfunction syndrome.

Sepsis continues to be a major clinical problem that is difficult to treat, as the pathophysiology of the disease is still unclear. Despite promising experimental strategies, therapeutic interventions have been largely unsuccessful. There is now increasing evidence that the disturbance of innate immunity during sepsis and multiorgan dysfunction syndrome (MODS) may be linked to uncontrolled activation of the complement system. Especially, the powerful anaphylatoxin C5a seems to play a key role in the development of immune paralysis. In this review, we describe our present understanding of the role of complement in the inflammatory response during sepsis and MODS.     

GM1 ganglioside partially rescues cultured dopaminergic neurons from MPP-induced damage: dependence on initial damage and time of treatment

GM1 ganglioside is believed to be important in promoting the recovery of neurons from injury. The present study assesses the ability of GM1 to repair or prevent the damage of dopamine neurons caused by the neurotoxin 1-methyl-4-phenylpyridinium (MPP⁺). Treatment of mesencephalic cell cultures with 2.5 μM MPP⁺ resulted in the loss of 30% of tyrosine hydoxylase (TH) immunoreactive neurons. In contrast, cultures administered 100 μM GM1 ganglioside for 3 days after toxin treatment contained nearly control numbers of TH⁺ neurons (97%). This reparative effect of GM1 was reflected in parallel increases in TH enzyme activity, dopamine and dopac levels. Cultures sustaining greater insult from higher doses of MPP⁺ (5.0–10.0 μM) did not benefit from ganglioside treatment, suggesting that rescue by GM1 depended on the degree of initial damage to cells. Moreover, the timing of ganglioside treatment was critical; pretreatment with GM1 alone did not prevent or attenuate the damage caused by subsequent incubation in 2.5 μM MPP⁺.     

Radiographic analysis of selective ligament sectioning at the carpal scaphoid: a cadaver study

Although scapholunate diastasis with rotatory subluxation of the scaphoid (stage I perilunar instability determined by Mayfield's classification) has been studied by several investigators, the exact contribution of the supporting ligaments is still being defined. We designed and executed an experimental study using six fresh-frozen cadaver specimens to demonstrate the radiographic changes seen on standard and stress wrist radiographs that correlate with the sequential sectioning of the scapholunate stabilizing ligaments. The radioscapho-lunate ligament, the palmar scapholunate interosseous ligament, the dorsal scapholunate interosseous ligament, and the radiocapitate ligament were sectioned sequentially to simulate a progressive wrist injury caused by an extension, intercarpal supination and ulnar deviation force. The results showed significant ligamentous injury must occur before commonly used radiographic limits are exceeded. The lateral scapholunate angle most closely reflected the progressive nature of this injury.     

Hereditary deficiency of antithrombin III, protein C and protein S: prevalence in patients with a history of venous thrombosis and criteria for rational patient screening.

Data in the literature on the prevalence of hereditary deficiency of the natural coagulation inhibitors are conflicting. We conducted a prospective study on 680 consecutive patients with a history of venous thrombosis to determine the prevalence of hereditary deficiency of antithrombin III (AT III), protein C(PC) and protein S(PS) and to establish selection criteria for rational patient screening. The mean age of the patients at investigation was 44.3 +/- 15.4 years, while that at the first thrombotic event was 38.5 +/- 14.8 years. The total prevalence of inhibitor deficiency states was 48/680 (7.1%). 19/680 patients (2.8%) had AT III-deficiency, 17 (2.5%) PC-deficiency, nine (1.3%) PS-deficiency and three (0.4%) a combined deficiency. In 37/48 deficient patients family studies were performed and the hereditary nature was established in 19 cases (2.8% of total patient population, six with AT III-deficiency, eight with PC-deficiency, four with PS-deficiency and one with a combined deficiency). Family studies in these 19 patients revealed 46 additional individual patients with a hereditary deficiency state. A positive family history was found in 15/19 (79%) with a proven hereditary deficiency state, in 153/619 (25%) of non-deficient patients and in 11/29 (38%) of deficient patients without established hereditary nature. The mean age at the first thrombotic event was significantly lower in patients with a hereditary deficiency state (26.8 years) compared with the other two groups (39.0 and 39.7 years, respectively). In all patients with a hereditary deficiency the first thrombotic event occurred before the age of 45 years.(ABSTRACT TRUNCATED AT 250 WORDS)