Evidence for neutrophil-related acute lung injury after intestinal ischemia-reperfusion

Intestinal ischemia-reperfusion injury is a common and important clinical event associated with the activation of an endogenous inflammatory response. Some of the mediators of this response may be involved in the pathogenesis of multiple organ system failure. The purpose of this study was to determine whether remote organ dysfunction--specifically, acute lung injury--occurs after intestinal ischemia-reperfusion injury. After an ischemia-reperfusion event in rat intestine, whole lungs were obtained for measurement of tissue adenosine triphosphate (ATP) and myeloperoxidase values, and evaluation of histologic condition. In addition, lung microvascular permeability was assessed by determination of the rate at which iodine 125-labeled bovine serum albumin sequestration in the extravascular compartment occurred. Lung tissue ATP levels were no different in sham-operated animals than in those that had undergone 120 minutes of intestinal ischemia. Within 15 minutes of gut reperfusion, however, lung ATP decreased from 3.82 +/- 0.27 to 1.53 +/- 0.90 x 10(-7) moles/50 mg tissue, p less than 0.05. Neutrophil accumulation in the lungs, estimated by tissue myeloperoxidase determination, increased sevenfold (0.13 +/- 0.02 to 0.97 +/- 0.25 units/gm, p less than 0.05) after 120 minutes of ischemia and 15 minutes of reperfusion. Lung microvascular permeability increased threefold after 120 minutes of intestinal ischemia and 120 minutes of reperfusion (0.10 +/- 0.01 vs. 0.35 +/- 0.05 [lung/blood counts per minute], p less than 0.05). Intestinal ischemia followed by reperfusion is associated with acute lung injury characterized by increased microvascular permeability, histologic evidence of alveolar capillary endothelial cell injury, reduced lung tissue ATP levels, and the pulmonary sequestration of neutrophils. These data confirm an acute lung injury associated with intestinal ischemia-reperfusion and suggest a possible pathogenic role for the neutrophil.     

Steal-prone coronary circulation in chronically instrumented dogs: isoflurane versus adenosine

The influence of isoflurane and adenosine on left ventricular myocardial blood flow was investigated in dogs chronically instrumented for measurement of systemic and coronary hemodynamics, regional myocardial contractile function (with ultrasonic sonomicrometers), and myocardial perfusion (by the radioactive microsphere method). An Ameroid constrictor was implanted on the left circumflex coronary artery to produce a progressive stenosis that gradually reduced vascular reserve of the distal perfusion territory. The depletion of reserve was evaluated by daily monitoring of the hyperemic response to adenosine. A stenosis of moderate severity was considered present when left circumflex reserve was attenuated by approximately 60-70%. During left circumflex stenosis development, the left anterior descending coronary artery was totally occluded for 2 min each hour eight times daily with a hydraulic occluder to stimulate coronary collateral development over a period of 9-13 days. Contractile dysfunction during and flow debt repayment after each brief occlusion were used to monitor coronary collateral development. After stenosis and collateral development had occurred, the left anterior descending coronary artery was permanently occluded to simulate a condition of multivessel coronary artery disease with enhanced collateral development. In separate groups of experiments, hemodynamics and myocardial perfusion were measured before and after administration of adenosine (0.54 and 1.08 mg/min) or isoflurane (1.1 and 1.9%, end-tidal) and in the presence of either agent during adjustment of diastolic aortic pressure and heart rate to control levels. Total left anterior descending coronary artery occlusion in the presence of a moderate left circumflex stenosis produced an increase in mean arterial and left ventricular end diastolic pressures. Isoflurane decreased arterial pressure, left ventricular systolic pressure, and positive rate of increase of left ventricular pressure (dP/dt50) without altering heart rate. Administration of the high concentration of isoflurane reduced blood flow in normal areas and in regions distal to the partial (from 1.05 +/- 0.10 to 0.76 +/- 0.11 ml.min-1.g-1) or total coronary occlusion (from 0.64 +/- 0.10 to 0.41 +/- 0.11 ml.min-1.g-1). However, when arterial pressure and heart rate were restored to levels present in the conscious state, perfusion in all zones was maintained at control levels (1.06 +/- 0.11 for the stenotic and 0.69 +/- 0.12 ml.min-1.g-1 for the occluded region). Ratios of transmural blood flow between occluded and normal or occluded and stenotic zones were not different from the conscious state during a constant aortic pressure and heart rate.(ABSTRACT TRUNCATED AT 400 WORDS)     

Migration of a K-wire from the distal radius to the heart

K-wires and Steinmann pins are used to provide internal fixation for fractures or osteotomies. In some instances, removal of the implant is planned and the implant is left long to facilitate its removal. In other instances, implant removal is not planned and the implant is cut off at the level of the bone. Migration of these implants to solid organs or body cavities has been reported. Extravascular migration may occur along tissue planes assisted by muscle motion. Large vessel penetration can occur and has been reported with subsequent migration of the implant to the heart. This case report documents the loosening of a K-wire used in the distal radius to supplement the fixation of a complex intra-articular fracture, migration of the implant along tissue planes, penetration into a peripheral vein, and continued migration of the implant to the heart. There are multiple reports documenting wandering bullets, venous catheter tips, and invasive monitoring devices in the extremities. This is only the second case report that the authors are aware of that confirms migration of an implant from the distal extremity to the heart.     

Effect of staphylococcal α-toxin on neutrophil migration and adhesiveness

The effect of staphylococcal-toxin on the chemotactic response of human polymorphonuclear leukocytes was studied by measuring the migration of-toxin-treated cells either through membrane filters toward C5a or under agarose towardN-formyl--methionyl--phenylalanine. At doses of 5 hemolytic units,-toxin depressed chemotactic responsiveness in both best systems. Further studies revealed that-toxin was also a potent granulocyte aggregant at doses similar to those necessary for depressed chemotactic capacity. It is proposed that the inhibitory effect of this membrane-active toxin on chemotactic function may be related to increased granulocyte adhesiveness and that the pathogenic properties of-toxin may in part by explained by these effects.     

Influence of methylenetetrahydrofolate reductase polymorphisms on efficacy and toxicity of methotrexate in patients with juvenile idiopathic arthritis

OBJECTIVE: To study the relationship of C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene to toxicity and efficacy of methotrexate (MTX) in patients with juvenile idiopathic arthritis (JIA). METHODS: Single nucleotide polymorphisms of the MTHFR gene were investigated by polymerase chain reaction and restriction enzyme analysis of DNA extracted from peripheral blood cells. The fasting plasma homocysteine concentration was analyzed by enzyme immunoassay. Clinical data of 58 patients with JIA treated with MTX were analyzed retrospectively. RESULTS: The 1298A/A genotype was present in 31 patients, 1298C/C in 4 patients, and 21 patients were heterozygous. The 677C/C genotype was present in 29 patients, 677 T/T in 3 patients, and 26 patients were heterozygous. In patients who presented the C allele of the A1298C polymorphism, improvement with respect to the number of swollen joints, the number of tender joints, and a decrease in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels occurred more frequently than in 1298 A/A homozygous patients (p < 0.05 for ESR, p < 0.01 for CRP, chi-square test). There was no relationship between the C677T polymorphism and the efficacy of MTX treatment. Forty-two adverse events were noted in 26 patients; gastrointestinal symptoms were most common (n = 20), followed by elevated serum levels of transaminases (n = 19) and hair loss (n = 3). There was no cytopenia. Patients with the heterozygous genotype 677C/T exhibited adverse events more frequently than patients with the homozygous C/C genotype (65% vs 31%; p < 0.05, chi-square test). The A1298C polymorphism, however, was not associated with occurrence of adverse events. Plasma homocysteine was elevated in 6 patients with up to 16.9 mmol/l. No association was found to a specific genotype or to adverse events. CONCLUSION: These preliminary data suggest an association of the MTHFR 677C/C polymorphism to a higher tolerability of MTX, and of the 1298A/A to lower clinical efficacy of MTX therapy in JIA.     

Pneumococcal sepsis after autosplenectomy in a girl with systemic lupus erythematosus

SIR, Autosplenectomy is infrequently described in systemic lupuserythematosus (SLE) [1, 2]. Asplenia is associated with highmortality due to Streptococcus pneumoniae infection [2–6].In this case report, we describe a girl who survived pneumococcalsepsis and meningitis. Our observation supports the applicationof pneumococcal vaccine in SLE patients. A 15-yr-old girl was treated with prednisolone (5 mg/48 h) andfosinopril due to SLE complicated by nephritis and arterialhypertension. After years of inactive     

Age dependence of epiphyseal ossification of the distal radius in ultrasound diagnostics

By determining the ossification stage of the distal radial epiphysis, it is possible to gain important information to help clarify the question of whether various legally relevant age limits have been exceeded. Any examination of the hand by means of projection radiography such as that used in conventional skeletal age diagnostics is strictly regulated for reasons of radiation hygiene. In many areas of the law, there are no basic legal provisions authorising the performance of X-ray examinations. The present study examines the applicability of ultrasound diagnostics in assessing ossification processes in the distal radius. To this end, the ossification stages of the distal radial epiphysis were determined in 306 female and 309 male study participants aged between 10 and 25 years. In the female gender, ossification stage III was determined at an age of 13.4 years at the earliest, and ossification stage IV at 15.0 years at the earliest. In the male gender, ossification stage III was not observed until 14.3 years, and ossification stage IV not until 15.2 years. In the practice of forensic age estimation in living persons, sonographic examination of the distal radius in areas of application with no legal basis for authorising X-ray examinations makes it possible to improve the accuracy of age diagnosis by including criteria of skeletal maturation. In view of the existing legislative basis for the use of X-rays on human subjects, the exposure of individuals to radiation can be minimised.