Significance of lung contusion in mortality following polytrauma. Possibilities for therapeutic influence

Multiple trauma is often associated with blunt thoracic injuries. Especially lung contusion can result in respiratory insufficiency and therefore a higher mortality rate. In our prospective study comparing 8 multiple trauma patients with and without associated lung contusion, we found that respiratory function was already significantly disturbed (decrease of paO2/FiO2 and increase of AaDO2, a rise in extravascular lung water (EVLW) both early after trauma and also with a second peak following the 4th day. This group (LK) developed significantly more cases of respiratory distress (ARDS). The disturbance of respiratory function seen initially was interpreted as a consequence of the direct mechanical impact, leading to the formation of interstitial fluid and hematoma. The frequent development of ARDS in the LK-group probably results from a pronounced activation of cellular and humoral mechanisms and therefore an enforced injury of the pulmonary capillary bed. A significant increase of pulmonary infections or the development of sepsis was not seen in the LK-group and is probably not responsible for the higher ARDS-rate in this group.     

Transplacental IgG Subclass Concentrations in Pregnancies at Risk of Haemolytic Disease of the Newborn

The relationship of haemolytic disease of the newborn (HDN) to the transplacental passage of the four IgG subclasses was assessed at varous gestational ages by comparing the maternal and fetal IgG subclass concentrations in 34 pregnancies at risk of HDN with those in 30 pregnancies not at risk. Higher maternal and fetal IgG1 levels were attained in pregnancies at risk of HDN than in pregnancies not at risk. In contrast, a slight decrease in maternal IgG2 and IgG4 levels occurred in pregnancies at risk of HDN, as compared with a slight rise in maternal IgG2 and IgG4 levels in pregnancies not at risk of HDN. Changes in fetal IgG2 and 4 concentrations in either type of pregnancy were very similar, showing only slight increases between the 19th and 34th week of gestation. A slight decrease in maternal IgG3 occurred in both types of pregnancy. In contrast, higher and fairly steady levels of fetal IgG3 were observed in fetuses not at risk of HDN throughout gestation, when compared with those in 'at risk' pregnancies. However, the statistical reliability of these results is not clear since only small numbers of samples were tested and because wide variations in IgG concentrations were observed. The IgG subclass concentrations in 50 paired maternal and cord blood samples were also measured and revealed that IgG1 levels were substantially higher in cord rather than maternal blood; cord and maternal IgG2, 3 and 4 levels, on the other hand, were fairly similar.     

Bombesin improves survival from methotrexate-induced enterocolitis.

OBJECTIVE: The authors determined whether bombesin could improve survival from methotrexate (MTX)-induced enterocolitis. SUMMARY BACKGROUND DATA: Bombesin prevents gut mucosal atrophy, which is produced by feeding rats an elemental diet. Administration of MTX produces a lethal enterocolitis in rats fed an elemental diet. METHODS: On treatment day 0, 60 rats were divided randomly into three groups and fed an elemental diet (Vivonex TEN, Sandoz, Minneapolis, MN) as the only source of nutrition. Groups were subdivided further to receive either saline or bombesin (10 micrograms/kg, subcutaneously, three times a day) beginning either on day 0 or day 14. Methotrexate (20 mg/kg, intraperitoneally) was given to all rats 14 days after the start of an elemental diet. RESULTS: Bombesin prevented the mucosal atrophy in the ileum produced by the elemental diet and significantly decreased mortality in rats given MTX (whether given as a pretreatment or at the time of MTX administration). CONCLUSION: Bombesin significantly improved survival in a lethal model of MTX-induced enterocolitis, possibly by maintaining gut mucosal structure. Administration of bombesin to patients receiving chemotherapy may be clinically useful in preventing the severe enterocolitis induced by various chemotherapeutic agents.     

Xenogeneic bone marrow transplantation: II. Porcine-specific growth factors enhance porcine bone marrow engraftment in an in vitro primate microenvironment

Abstract: Establishment of mixed bone marrow chimerism in pig-to-primate transplantation, as a means of inducing specific immune tolerance, will require that both immune and nonimmune barriers be overcome. As a preliminary step in evaluating nonimmune barriers in this system, we have developed an in vitro model of engraftment in which long-term culture of porcine bone marrow-derived hematopoietic cells is supported on preformed primate bone marrow stromal layers. In the absence of cytokine supplementation, primate stromal cells were unable to support long-term porcine hematopoiesis in these cultures. Supplementation with porcine Steel Factor was required for long-term maintenance of hematopoietic progenitor cell content and total hematopoietic activity. Addition of porcine IL-3, in combination with porcine Steel Factor, increased long-term progenitor cell content and hematopoietic activity on primate stroma to levels comparable to that obtained in cultures on porcine stroma. The combination of porcine GM-CSF and Steel Factor increased progenitor cell content and hematopoietic activity early in the cultures, but had little effect in long-term cultures. The Steel Factor and IL-3 combination was species-specific in its action in these cultures, as the corresponding human cytokines were unable to effectively support long-term porcine hematopoiesis. Likewise, the combination of porcine cytokines had only minimal effects on long-term bone marrow culture of primate CD34+ cells I on primate stroma.     

Occupational exposure to hazardous substances and risk of cancer in the area of the mouth cavity, oropharynx, hypopharynx and larynx. A case-control study

A case-control study of squamous cell carcinoma of the upper aerodigestive tract conducted in Heidelberg and Giessen (FRG) provided information on occupational factors in 200 patients and 800 controls (adjusted to sex, age and area of living; 4:1 matched design). The number of subjects exposed to wood dusts, organic chemicals, coal products or to cement was significantly elevated in the tumour group. An increased risk for head and neck cancer was observed after exposition to wood dust (RR = 2,2), organic compounds (RR = 2,4), coal products (RR = 2,7) and especially to cement (RR = 4,4). The cancer risk due to cement exposition showed a positive correlation to the duration of exposition and remained significantly elevated after adjustment for alcohol and tobacco consumption.     

Effect of maternal administration of thyrotropin-releasing hormone or DN1417 on functional and morphologic fetal rabbit lung maturation and duration of survival after premature delivery

Though maternal treatment with thyrotropin-releasing hormone (TRH) for prevention of hyaline membrane disease has been utilized, precise mechanisms of TRH in accelerating fetal lung maturation remain unclear. We studied the effect of maternally administered TRH or DN1417 (an analog of TRH) on functional and morphologic fetal rabbit lung maturation and the duration of survival after premature delivery. Because DN1417 retains the neurotransmitter but not the neuroendocrine effects of TRH, this study enables us to determine which of these effects was responsible for enhancement of lung maturation. TRH or DN1417 (0.2 mg/kg/dose) or saline was injected intravenously into New Zealand White rabbit does 48, 36, 24, 12 and 2 h prior to sacrifice on day 27 of gestation. Functional pulmonary maturity was assessed by pressure-volume hysteresis, and morphologic maturity was assessed by histologic technique. Maternal administration of TRH or DN1417 enhanced both functional and morphologic fetal lung maturation as well as the duration of neonatal survival after premature delivery. We propose that the effect of TRH in fetal lung maturation is due to neurotransmitter rather than neuroendocrine effects.     

INCREASED RATE OF ETHANOL ELIMINATION AND ELEVATED BLOOD ACETATE IN ASTHMATICS ON CORTICOSTEROID, BETA-2-SYMPATHICOMIMETIC AND THEOPHYLLINE TREATMENT

The rate of ethanol elimination and blood acetate concentrationsafter a peroral dose of alcohol were measured in eight asthmaticpatients receiving high-dose corticosteroid, sustained releasetheophylline and beta-2-sympathicomimetic treatment and in eightnonalcoholic, healthy controls. Mean ethanol elimination rate(ER) and mean blood acetate concentration (AC) were significantly(P<0.01) higher in asthmatics (ER=134.8 ± 12.9 mg/kg/hr,AC = 1.13± 0.25 mM) than in controls (ER = 100.2 ±12.3 mg/kg/hr, AC = 0.64 ± 0.10 mM). In the asthmaticsthere was a significant negative correlation between the ageand the rate of ethanol elimination (r = –0.890, P <0.01); in the control group, however, this correlation was oflower degree (r = –0.423) and did not achieve statisticalsignificance. Enhanced ethanol metabolism in asthmatics is possiblydue to the effect of drugs. Our results suggest that ethanolelimination rate is increased in asthmatics receiving medicationand that the effect is most significant in younger age groups.     

Stereoselectivity of actions of the calcium sensitizer [+]-EMD 60263 and its enantiomer [-]-EMD 60264

The thiadiazinone derivative [+]-EMD 60263 ((+)-5-(1-(α-ethylimino-3,4-dimethoxybenzyl)-1,2,3,4- tetrahydroquinoline-6-yl)-6-methyl-3,6-dihydro-2H-1,3,4 -thiadiazine-2-on) is a Ca²⁺-sensitizing agent with only minor phosphodiesterase inhibitory activity. Our aim was to characterize the inotropic and electrophysiological effects of [+]-EMD 60263 and its enantiomer [-]-EMD 60264 in several cardiac muscle preparations. The Ca²⁺-sensitizing activity resided in the [+]-enantiomer only. [+]-EMD 60263 (3 μM) shifted the EC₅₀ of Ca²⁺ for contractile activation of skinned fibers of pig heart from 2.41 μM to 0.73 μM, whereas [-]-EMD 60264 (30 μM) was ineffective. In Langendorff-perfused guinea pig hearts, [+]-EMD 60263 and [-]-EMD 60264 induced concentration-dependent positive and negative inotropic effects, respectively; both enantiomers reduced spontaneous heart rate but did not influence perfusion pressure. The maximum increase in force of human atrial trabeculae was 35 % of pre-drug control with [+]-EMD 60263 in comparison to 113 % with forskolin. In guinea-pig papillary muscles, [+]-EMD 60263 and [-]-EMD 60264 had opposite inotropic responses, however, both agents similarly prolonged action potential duration. Both enantiomers concentration-dependently blocked the rapidly activating component I_Kr of the delayed rectifier in guinea-pig myocytes. The block saturated at potentials positive to +30 mV, closely resembling the effects of the antiarrhythmic agent E-4031 which had been originally used to define I_Kr. It is concluded, that the positive inotropic action of [+]-EMD 60263 can be explained by prevalence of the Ca²⁺-sensitizing effect. The accompanying prolongation in action potential duration is caused by block of the I_Kr component of the delayed rectifier. While the inotropic effects are stereoselective, most of the electrophysiological actions are clearly independent of sterical configuration. The combination of Ca²⁺-sensitizing with class-III antiarrhythmic action may provide an interesting pharmacological profile of potential therapeutic use. Received: 7 January 1997 / Accepted: 25 February 1997