A murine model of deep vein thrombosis: characterization and validation in transgenic mice

Deep vein thrombosis (DVT) occurs with high prevalence in association with a number of risk factors, including major surgery, trauma, obesity, bed rest (> 5 days), cancer, a previous history of DVT, and several predisposing prothrombotic mutations. A novel murine model of DVT was developed for applications to preclinical studies of transgenically constructed prothrombotic lines and evaluation of new antithrombotic therapies.A transient direct-current electrical injury was induced in the common femoral vein of adult C57BI/6 mice. A non-occlusive thrombus grew, peaking in size at 30 min, and regressing by 60 min, as revealed by histomorphometric volume reconstruction of the clot. Pre-heparinization greatly reduced clot formation at 10, 30, and 60 min (p < 0.01 versus non-heparinized). Homozygous FactorV Leiden mice (analogous to the clinical FactorV Leiden prothrombotic mutation) on a C57Bl/6 background had clot volumes more than twice those of wild-types at 30 min (0.121 +/- 0.018 mm3 vs. 0.052 +/- 0.008 mm3, respectively; p < 0.01). Scanning electron microscopy revealed a clot surface dominated by fibrin strands, in contrast to arterial thrombi which showed a platelet-dominated structure. This new model of DVT presents a quantifiable approach for evaluating thrombosis-related murine transgenic lines and for comparatively evaluating new pharmacologic approaches for prevention of DVT.     

Effects of ethnicity on skeletal maturation: consequences for forensic age estimations

An X-ray of the hand is an important method in forensic science for estimation of the age of juvenile suspects with uncertain date of birth. Relevant X-ray standards for evaluation of skeletal maturity are available for white US Americans as well as for North and Central Europeans. The applicability of these standards to members of ethnic groups different from the reference population has been the subject of controversial discussion. More than 80 publications were analysed with the view to finding out whether skeletal maturation is affected by ethnic identity. It was concluded that skeletal maturation takes place in phases which are identically defined for all ethnic groups. Time-related differences in passing those stages of skeletal maturation within the relevant age group appear to be unaffected by ethnic identity. It is the socio-economic status of a given population which is of decisive importance to the rate of ossification. The application of X-ray standards to individuals of a socio-economic status lower than that of the reference population usually leads to underestimation of that person’s age. In terms of criminal responsibility, this is of no adverse effect on the person concerned. Received: 25 February 1999 / Received in revised form: 6 August 1999     

Self concept and object relations of patients with affective disorders--individual centered diagnosis with the repertory-grid technique

Significant dimensions of the self concept and the object relations of 127 depressive patients and 34 orthopaedic patients were investigated with the repertory-grid-technique. Self concept and object relations were compared by means of nomothethically used idiographic results after recovery from manifest depression. The object relations of the depressive sample were characterised by the dimension "symbiotic near"; "ambivalent" and "indifferent" partnership relationships were found much more frequently in the controls. The idiographic results contribute to a differentiation of the spectrum of affective disorders. They underline the importance of the interpersonal dimension of depression and may be used as a basis of a therapeutic orientation.     

Americans with disabilities act: recent and pending u.s. Supreme court decisions and implications for spine professionals

This article highlights recent and pending United States Supreme Court cases interpreting employment provisions of the Americans with Disabilities Act and discusses their implications for spine professionals. The implications include how Spine readers approach evaluations of employees and job applicants with disabilities and workplace accommodations in light of the recent decisions. The cases pending before the Supreme Court involve orthopedic impairments and the "reasonableness" of certain workplace accommodations. Increasingly, spine professionals will be called on to assist in the analysis of these issues. This article will familiarize Spine readers with the legal interpretations under the Americans with Disabilities Act of "disability," "mitigating measures," "qualified individual," and "reasonable accommodations." It illustrates the ways in which spine professionals may be called on to help interpret and apply qualification and safety standards under the Americans with Disabilities Act to assist individuals, employers, attorneys, and other stakeholders in the employment of people with disabilities.     

Influence of desflurane on regional distribution of coronary blood flow in a chronically instrumented canine model of multivessel coronary artery obstruction

The influence of desflurane on myocardial perfusion measured by a microsphere technique during a total occlusion of the left anterior descending coronary artery and concomitant moderate or severe stenosis of the left circumflex coronary artery was evaluated in chronically instrumented dogs. Hemodynamics, regional contractile function, and myocardial blood flow were measured during the conscious state and after anesthesia with desflurane (8.2%-9.2% and 12.5%-12.7%) with and without control of arterial pressure. Total left anterior descending occlusion produced in combination with a left circumflex coronary artery stenosis significantly (P less than 0.05) increased heart rate and left ventricular end diastolic pressure in the absence of desflurane anesthesia. Desflurane, administered only in the presence of left anterior descending occlusion and left circumflex stenosis, significantly (P less than 0.05) decreased mean arterial pressure, left ventricular systolic pressure, and left ventricular positive dP/dt50 without change in heart rate. Blood flow to the subendocardium of normal myocardium was reduced during the high concentration of desflurane (P less than 0.05), but perfusion of the subepicardium and midmyocardium was maintained at conscious levels. When the left circumflex stenosis was of moderate severity, only blood flow to the subendocardium distal to the stenosis was reduced by desflurane (P less than 0.05). In the presence of a severe stenosis, perfusion was decreased in the subepicardium, midmyocardium, and subendocardium of the stenotic zone (P less than 0.05). During the reduction in arterial pressure produced by desflurane, collateral blood flow in the left anterior descending region was reduced in dogs with either a moderate or severe left circumflex stenosis (P less than 0.05). When arterial pressure and heart rate conditions observed in the postocclusion conscious state were restored during the high concentration of desflurane, myocardial blood flow in all regions returned to those levels present in the conscious state (P less than 0.05). Ratios of flow between occluded and normal zones were decreased when hypotension produced by desflurane was uncontrolled, but when arterial pressure and heart rate were adjusted to conscious postocclusion levels using partial thoracic aorta occlusion and atrial pacing, the ratio remained at conscious control levels regardless of the degree of left circumflex stenosis severity (P less than 0.05). Results of this investigation indicate that desflurane does not redistribute blood flow away from collateral-dependent myocardium to other regions via a "coronary steal" mechanism in a chronically instrumented canine model of multivessel coronary artery disease.     

Electron microscopic stereology of capillary endothelial cells and cardiomyocytes in artificially arrested canine hearts

In open heart surgery and transplantation, sufficient structural preservation of the myocardium immediately following cardioplegic arrest is a precondition for overcoming ischemia and for resumption of postischemic function. Therefore, we compared the protective effect of three clinically applied cardioplegic solutions with fibrillating and beating hearts using structural criteria. Left ventricular samples were taken from (1) beating, or (2) fibrillating or arrested hearts following coronary perfu-sion with (3) St. Thomas' Hospital solution, (4) histidine tryptophane ketoglutalate (HTK) (Custodiol), or (5) University of Wisconsin (UW) solution and fixed by immersion. Ultrastructural differences in the swelling of capillary endothelial cells and myocytes were quantitatively evaluated using stereological methods. Endothelial cells were somewhat more swollen after St. Thomas perfusion than those in beating and fibrillating hearts. HTK-arrested hearts showed significantly lower values for cellular edema than beating hearts. UW perfusion resulted in the (significantly) lowest degree of endothelial cell edema. Edematous changes in myocytes were significantly greater in St. Thomas-arrested hearts than in UW- or HTK-arrested hearts. Cardiomyocyte edema in beating and fibrillating hearts was comparable to that in St. Thomas-perfused hearts. Thus, the stereol-ogical analysis revealed significant differences between cardioplegic solutions in structural preservation of myocardial ultrastructure.     

Prolongation of the QT interval by enflurane, isoflurane, and halothane in humans

Previous investigations in laboratory animals have documented the ability of the volatile anesthetics to prolong the QT interval and the QT interval corrected for level of heart rate, QTc. The purpose of the present investigation was to evaluate the direct electrocardiographic and hemodynamic effects of enflurane, isoflurane, and halothane in healthy, unpremedicated patients using an inhalation induction to avoid the confounding effects of other anesthetic agents. Experiments were conducted in 22 adult male patients, (ASA physical status I or II) divided into three groups given either enflurane (n = 6), isoflurane (n = 8), or halothane (n = 8) anesthesia. Twenty-four-hour preoperative, preinduction, and postinduction hemodynamic and electrocardiographic measurements were obtained. Anesthetic blood concentrations, levels of plasma electrolytes, and arterial blood gas tensions were also quantitated. Halothane administration (0.81 +/- 0.06 mM) did not significantly alter the PR interval or QRS duration but significantly increased the QT (0.38 +/- 0.01 to 0.45 +/- 0.01 s) and QTc intervals (0.39 +/- 0.01 to 0.44 +/- 0.02 s). Isoflurane anesthesia (1.04 +/- 0.11 mM) did not significantly change QRS duration or PR and QT intervals but significantly prolonged the QTc interval (0.42 +/- 0.01 to 0.47 +/- 0.14 s). Similarly, enflurane anesthesia (2.16 +/- 0.13 mM) significantly prolonged the QTc (0.40 +/- 0.01 to 0.46 +/- 0.14 s) without change in QRS duration or PR and QT intervals. Plasma electrolyte levels and arterial gas tensions remained within normal limits in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Histamine: a promoter of xanthine oxidase activity in intestinal ischemia/reperfusion.

Xanthine oxidase (XO)-derived oxygen radicals are thought to play an important role in the intestinal injury resulting from ischemia and reperfusion. In vitro data shows enhanced XO activity in the presence of histamine. Histamine is known to be released during intestinal ischemia and reperfusion. The purpose of this study was to evaluate the relationship between histamine and XO in vivo in intestinal ischemia/reperfusion injury. Using an established model of gut ischemia and reperfusion, portal venous plasma was obtained and assayed for histamine levels, XO activity, and xanthine dehydrogenase (XD) activity following injury. Intestinal ischemia for 120 minutes resulted in a 200% increase in plasma histamine levels (263.4 +/- 36.9 nmol/mL control, v 548.7 +/- 35.1 nmol/mL experimental, P less than .05). Reperfusion for 15 minutes resulted in a further increase in plasma histamine (to 658.3 +/- 33.9 nmol/mL), compared with 120 minutes of ischemia alone. No significant change in plasma XO activity resulted after simple ischemia for 120 minutes. However, XO activity doubled within 15 minutes of reperfusion of the ischemic intestine (6.37 +/- 0.53 nmol O2- per milliliter per minute v 3.12 +/- 0.25 nmol O2- per milliliter per minute, P less than .05). Reperfusion for 60 minutes resulted in the maximal observed increase in plasma XO activity (9.49 +/- 0.67 nmol O2- per milliliter per minute). Analysis of XD activity demonstrated no significant decrease compared with controls until 120 minutes of ischemia and 60 minutes of reperfusion (1.62 +/- 0.49 nmol uric acid per milliliter per minute at 60 minutes of reperfusion, versus 5.02 +/- 0.52 nmol uric acid per milliliter per minute control, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)