NATURE AND HEALING OF TIBIAL SHAFT FRACTURES IN ALCOHOL ABUSERS

Alcohol abuse is associated with an increased risk of osteopeniaand fractures. Previous histomorphometric studies on iliac crestbone have found decreased bone formation and increased boneresorption in alcohol abusers but it has not been establishedwhether alcohol abuse has any effect on the anatomical locationor the healing time of tibial shaft fractures. We studied, retrospectively,199 adult male patients hospitalized for isolated tibial shaftfracture in the city of Malmö, Sweden, between 1980 and1990. Forty-nine of the patients had earlier been registeredat the Department of Alcohol Diseases and were judged to beproblem drinkers. Abusers sustained their tibial shaft fracturesmore often by falling at ground level (P<0.0001) or froma higher level (P=0.009) and the fractures were more often obliquethan transverse (P=0.002) as compared with non-abusers. Healingtime was impaired in abusers who had sustained a transversefracture (P=0.035), but no difference was observed in healingtime in those with an oblique fracture. We found no differencebetween the abusers and the non-abusers regarding duration ofhospital stay, fracture location, amount of displacement, occurrenceof open fractures or the rate of complications.     

Generation of iC3 at the Interface between Blood and Gas

Earlier studies have shown that C3 can be denatured when blood comes in contact with a polystyrene surface. This study was undertaken to see if similar denaturation of C3 occurs at the gas-plasma interface which is found in all kinds of oxygenator used during cardio-pulmonary operations. An in vitro system consisting of gas bubbling through human blood, serum or plasma was used. The generation of C3a, as an indicator of complement activation, and iC3 and iC3 fragments were monitored. Both C3a and iC3/iC3 fragments levels were increased during bubbling. In contrast to the C3a level, no reduction in iC3/iC3 fragments formation was seen in the presence of EDTA, indicating that it was independent of complement activation. The rate of iC3/iC3 fragments generation was unaffected by the composition of the gas (pure oxygen, pure nitrogen or air), suggesting that the denaturation of C3 indeed occurred at the serum-gas interface. C3 and iC3/iC3 fragments were isolated from bubbled EDTA-chelated serum by PEG precipitation and chromatography on FPLC, using a Mono S column and detected by two ELISAs, specific for native C3 and iC3/iC3 fragments. After 240 min approximately 20% of the total amount of C3 consisted of intact iC3 and it was confirmed that this population bound to human erythrocytes.     

Interleukin-4 (IL-4) Enhances Homotypic Adhesion of Activated B-Chronic Lymphocytic Leukaemia (B-CLL) Cells via a Selective Up-Regulation of CD54

It is well established that cell-to-cell contact modifies cytokine signalling but little is known on the role of homotypic cell adhesion for proliferation and differentiation of B cells. Homotypic adhesion involves mainly the interaction between the adhesion molecules Leukocyte Function Antigen-1 (LFA-1) and its ligand CD54 (ICAM-1). A well-characterized B-chronic lymphocytie leukaemia (B-CLL) clone (1–83) was used as a source of monoclonal B cells inducible to DNA synthesis and differentiation by using 12-O-tetradecanoyl-phorbol-13-acetate(TPA) in combination with intcrleukin-4 (IL-4) and thioredoxin(Trx)-containing supernatant from a T-cell hybridoma (BSF-MP6). This paper shows that IL-4 alone was able to induce aggregation of B-CLL cells and to strongly enhance TPA+BSF-MP6-induced aggregalion. The results from studying the expression of CD11a and CD18, the two suhunits of LFA-1, and CD54 during stimulated DNA synthesis and differentiation suggest that IL-4-induced. or enhanced, aggregation was mainly mediated by a selective up-regulation of CD54. It was further demonstrated by antibody blockade to either CD11a, CD18 or CD54 that aggregation could be inhibited without affecting induced DNA synthesis or differentiation.     

Association between inflammation and epithelial damage-restitution processes in allergic airways in vivo

Background Associations between allergen challenge-induced sites of epithelial damage and the distribution of leucocytes and extravasated plasma remain unexplored. Objective To study neutrophils, eosinophils, and fibrinogen at allergen challenge-induced patchy epithelial damage-restitution sites in guinea-pig trachea. Methods After local challenge tracheal tissue (cryo sections and whole-mounts) and lumen (selective tracheal lavage) were examined at 1, 5, and 24 h. Eosinophils, neutrophils and fibrinogen were identified by histochemistry. Results Neutrophils increased markedly in tracheal lavage fluids and in tissue and were strongly associated with the challenge-induced epithelial craters of damage-restitution. At 1 and 24 h eosinophils were increased in the tracheal lumen whereas the surrounding tissue displayed a reversed pattern. Gels rich in fibrinogen, neutrophils, and eosinophils were present in epithelial crater areas, protruding into the lumen. Clusters of free eosinophil granules, Cfegs, released through lysis of eosinophils, and neutrophils with long cytoplasmatic protrusions abounded in these crater areas. Conclusions The present findings provide important new insights into allergic airways where sites of epithelial damage-restitution processes emerge as the major loci for eosinophil, neutrophil, and plasma protein activities, the latter likely causing leukocyte adhesion and activation in vivo. The disttibution of eosinophils in this study suggests roles of these cells both in airway mucosa and in regional lymph nodes. Based on the present study we also propose that lysis of eosinophils and Cfegs generation are a major paradigm for activation of these cells in vivo.     

Validity of a postal questionnaire with regard to the prevalence of myocardial infarction in a general population sample

In order to evaluate the possibility of finding persons whohave suffered a myocardial infarction (MI) by postal questionnaire,a self-administered questionnaire was sent to a random sampleof 4400 men aged 45–64 years, drawn from the general population.The response rate was 95%. 176 men indicated that they had beenhospitalized for MI, out of which 124 cases could be verifiedfrom medical records. Of the remaining men, 33 had evidenceof cardiovascular disease (CVD) in their records but no MI,and 19 men had no evidence of CVD. The sensitivity (estimatedfrom a subsample) was 100% and the specificity 98.7%. The predictivevalue was 100% for a negative response and 70.5% for a positiveresponse. The 33 positive responders whose MI could not be verified butwho had evidence of CVD had characteristics fairly similar tothe responders with verified Mis. However, the 19 positive responderswhose MI could not be verified and who had no evidence of CVDhad characteristics that were dissimilar from the MI group aswell as from the negative responders. The questionnaire thus identified all the MI cases. The needfor validation can be limited to the relatively small groupof positive responders.     

Acute effects of acetazolamide on cerbral blood flow in man

We have followed the time course of the effect of the carbonic anhydrase inhibitor acetazolamide injected i. v. in unanesthetized healthy human beings. The dose administered was 500 mg as a bolus. Cerebral blood flow (CBF) was measured continuously before, during and after the injection, using a pulsed ultrasound doppler system, which measured the instantaneous mean velocity across the lumen of the internal carotid artery, just below its entrance into the skull. Ventilation, heart-rate, end-expiratory PCO₂- arterial PCO₂, pH and systemic blood pressure was also measured. We found that acetazolamide caused a rise in CBF which could be detected as early as 2 min after the injection. A maximal average response of 75% increase in CBF was seen after 25 min. The half-time of the declining phase of the response was 95 min. There were no systematic differences in the CO₂ reactivities, given as ACBF/ΔPACO₂ in % of CBF at normocapnia, before and after acetazolamide injection, regardless of the absolute PACO₂ level. The present dose of the drug caused no change in ventilation, alveolar and arterial PCO₂ or in arterial blood pH indicating that the carbonic anhydrase was not fully inhibited. Our observations show that acetazolamide nevertheless caused a rapid vasodilation in the brain and over a wide range of PCO₂′s. We suggest that this agent has a local vasodilator effect on the cerebral arterioles, unrelated to its specific effects as a carbonic anhydrase inhibitor.     

Ultrasound study of the cranial venous system in the human new-born infant and the adult

A pulsed doppler ultrasound technique has been used to measure changes in blood velocities in the superior sagittal sinus, the jugular veins and intracranial and extracranial arteries in 13 neonates, and in the jugular veins and an extracranial artery in 13 adults, during unilateral and bilateral jugular venous compressions. The results have enabled us to determine how the subject under examination functionally uses his cranial venous drainage system in the resting state, and whether or not he can shunt obstructed venous flow through other cranial venous channels. We have found great variability between the subjects. In the resting situation the range of possibilities from total dependence on one jugular vein alone to usage of both jugular veins and the vertebral veins exists. Shunting of blood on jugular compression from either or both jugular veins to the vertebral veins may occur, and contralateral shunting between the jugular veins may be possible in both directions, in one direction or not at all.     

Effect of a new inhibitor of lipid peroxidation on kidney function after ischaemia-reperfusion. A study on rat and rabbit kidneys

Lipid peroxidation of mitochondrial and cell membrane structures is the final step in the oxygen radical-induced damage observed at reperfusion of kidneys after ischaemia. We compared the ability of an indeno-indol compound (code name H290/51) with that of α-tocopherol to inhibit lipid peroxidation in reoxygenated isolated rat renal tissue in vitro measured as production of TBARS (thiobarbituric acid reactive substances). H290/51 was 100 times more efficient than α-tocopherol. Treatment of rats in vivo with H290/51 in a dosage giving a plasma concentration of 500 nmol L^-1 inhibited TBARS production measured in vitro by 80%. Treatment of rabbits with H290/51 almost completely inhibited radical production at reperfusion after 60 min of ischaemia measured with spin trap technique using OXANOH (2-ethyl-3-hydroxy-2,4,4-trimethyloxazolidine) as a spin trap. Furthermore, such pretreatment significantly improved kidney function and survival of rabbits subjected to 60 min of ischaemia to the left kidney and contralateral nephrectomy. These studies stress the importance of inhibiting lipid peroxidation to prevent the ischaemia-reperfusion damage and furthermore suggest a role for treatment with antioxidants like H290/51 in clinical practice, e.g. at reconstructive renal surgery and transplantation.     

Effects of sympathetic stimulation on cerebral and ocular blood flow Modification by hypertension,hypercapnia, acetazolamide,PGI2 and papaverine

The effect of unilateral, electrical stimulatio of the cervical sympathetic chain in rabbits anesthetized with pentobarbital sodium and vasodilated by hypercapnia, acetazolamide, papaverine or PGI₂ was investigated to determine to what extent the sympathetic nerves to the brain and the eye cause vasoconstriction and prevent overperfusion in previously vasodilated animals. Evans blue was given as a tracer for protein leakage. Blood flow determinations were made with the labelled microsphere method during normotension and acute arterial hypertension. Hypertension was induced by ligation of the thoracic aorta and in some animals metaraminol or angiotensin was also used. Acetazolamide caused a two to threefold increase in cerebral blood flow (CBF) and hypercapnia resulted in a fivefold increase. CBF was not markedly affected by papaverine or PGI₂. In the choroid plexus, the ciliary body and choroid, papaverine and hypercapnia caused significant blood flow increases on the control side. Sympathetic stimulation induced a 12 % blood flow reduction in the brain in normotensive, hypercapnic animals. Marked effects of sympathetic stimulation at normotension were obtained under all conditions in the eye. In the hypertensive state the CBF reduction during sympathetic stimulation was moderate, but highly significant in hypercapnic or papaverine-treated animals as well as in controls. Leakage of Evans blue was more frequently seen on the nonstimulated side of the brain. In the eye there was leakage only on the control side except in PGI₂-treated animals where 2 rabbits had bilateral leakage. The effect of sympathetic stimulation on the blood flow in the cerebrum and cerebellum in vasodilated animals seems to be small or absent if the blood pressure is normal. In the eye pronounced vasoconstriction occurs under these conditions. In acute arterial hypertension sympathetic stimulation protects both the cerebral and ocular barriers even under conditions of marked vasodilation.     

T-Cell Response to Purified Protein Derivative after Removal of Langerhans'' Cells from Epidermal Cell Suspensions Containing Keratinocytes Expressing Class II Transplantation Antigens

In a previous study we observed that human epidermal cell (EC) suspensions containing HLA-DR-expressing keratinocytes showed an amplified T-cell response to purified protein derivative (PPD). To evaluate further the possible immunological importance of class II transplantation antigens on keratinocytes we have compared the T-cell response to PPD in the presence of the following stimulator cells: EC suspensions from normal skin, or EC from tuberculin-reactive skin with or without removal of Langerhans' cells. The proliferation of purified T lymphocytes from peripheral blood in response to PPD in the presence of various concentrations of autologous EC was measured by [3H]thymidine incorporation on day 6. In 3 experiments out of 4 the EC from tuberculin-reactive skin, containing 28-76% HLA-DR-expressing cells as judged by immunocytochemistry (which also revealed fairly numerous HLA-DQ/-DP-expressing keratinocytes and a slight increase in CD36- and CD4- but not CD1-expressing cells), induced a more pronounced T-cell response to PPD than did normal EC. This was not the case in the fourth experiment, in which a small number of HLA-DR-(15%) and few if any HLA-DQ-/-DP-expressing keratinocytes were found. Immunomagnetic removal of CD1-reactive Langerhans' cells from the tuberculin-reactive EC suspensions resulted in a reduction of the T-cell response to PPD, in most cases down to background level (T cells alone + PPD). This study does not support the hypothesis that HLA-DR-expressing keratinocytes can in themselves act as antigen-presenting cells.